Rajesh Yadav | Dr. Hari Singh Gour University, Sagar (A Central University) (original) (raw)

Papers by Rajesh Yadav

The Open Microbiology Journal, 2021

Phylogenetic analysis of different ecosystems has shown that the number of microbial communities ... more Phylogenetic analysis of different ecosystems has shown that the number of microbial communities in a single sample exceeds their cultured counterparts. Microbes have been found throughout nature and can thrive in adverse conditions. Besides inhabiting diverse environments, they also play a key role in the maintenance of the ecosystem. Most of these microbes are either unculturable or difficult to culture with conventional culturing methods. Metagenomics is an emerging field of science that has been in the light for a decade and offers a potential way to assess microbial diversity. The development of metagenomics opens new ways to study genetic material directly from the environmental samples. DNA sequencing and synthesis technologies are making it possible to read and write entire genomes. The huge amount of data obtained from genome sequencing inevitably requires bioinformatics tools to handle and further process them for analysis. Advances in DNA sequencing and high-performance c...

Biomarkers, 2016

In the recent years the uses and applications of pesticides has been tremendously increased and t... more In the recent years the uses and applications of pesticides has been tremendously increased and therefore the risk of exposure to human also increased with adverse health effects including neurotoxicological alterations. Pesticide residues and their metabolites have been detected in dietary constituents, food materials, tissues, maternal blood and breast milk, which are further linked to the developer and neurological disorders. Biomarkers are considered as an important determinant for the examination of organ function, investigation of diseased conditions and therefore could be useful for the analysis procedure. In view of the increasing risk of human health through pesticide exposure, the present review has been focused on the use of biomarkers in pesticide induced biochemical and neurochemical alterations which could help in biomonitoring studies of populations exposed to pesticides along with the main routes of uptake and mechanism of action, which can be used to monitor risk as...

International Journal of Nutrition, Pharmacology, Neurological Diseases, 2018

Introduction: In our earlier studies, we reported that arsenic-induced enhanced oxidative stress,... more Introduction: In our earlier studies, we reported that arsenic-induced enhanced oxidative stress, apoptosis, immunotoxicity and inflammation in the spleen and thymus of mice and hepatotoxicity have been protected through treatment with Emblica officinalis (amla). The present study is focused on to the efficacy of amla in mitigation of arsenic-induced dyslipidemia and alterations in inflammatory biomarkers in the blood of mice. Materials and Methods: Mice were randomly divided into four groups and treated with sodium arsenite (3 mg/kg b.w., per os), amla (500 mg/kg b.w., per os) and simultaneously with arsenic and amla daily for 30 days. Results: Arsenic treatment altered the hematological and lipid profile by increasing total cholesterol (TC), triglyceride (TG), phospholipid (PL) and low-density lipoprotein (LDL) levels and decreasing high-density lipoprotein (HDL) levels as compared to controls. Treatment with arsenic also disturbed the levels of inflammatory biomarkers. Concurrent...

Journal of Biochemical and Molecular Toxicology, 2020

Earlier, we reported that chronic exposure to pesticides causes a reduction in the acetylcholines... more Earlier, we reported that chronic exposure to pesticides causes a reduction in the acetylcholinesterase activity and hematological and biochemical alterations in agriculture workers. In continuation with that, the present study aimed to investigate the pesticide‐induced neurochemical imbalance and its association with behavior alterations in agricultural workers. A significant increase in depressive symptoms, assessed by the Beck Depression Inventory‐II was observed in pesticide exposed workers as compared to the unexposed. A decrease in the level of dopamine in plasma and levels of dopamine, 3,4‐dihydroxyphenylacetic acid, homovanillic acids, norepinephrine, serotonin, and hydroxyindoleacetic acid in urine was also observed. An increase in the levels of MAO‐A and MAO‐B has also been observed in these individuals. The decreased levels of neurotransmitters in the blood and urine have been linked with increased levels of MAO and pesticide residues in plasma and urine. Furthermore, the...

DARU Journal of Pharmaceutical Sciences, 2019

Background Mitochondrial impairments due to free radicals are implicated in a wide range of neuro... more Background Mitochondrial impairments due to free radicals are implicated in a wide range of neurotoxicological alterations. Curcumin, an active ingredient of turmeric has shown protective efficacy against oxidative damage due to its strong antioxidant potential, but its efficiency is restricted due to low bioavailability in the mitochondria. In view of this, we have synthesized mitochondria-targeted curcumin (MTC) with an aim to investigate its efficacy against rotenone-induced oxidative damage in mice and isolated mitochondria. Methods MTC was synthesized by attaching the triphenylphosphonium cation (TPP) as a cationic carrier to the curcumin to assess its protective efficacy in rotenone-induced in-vitro and in-vivo toxicity in mice. Results In-vitro treatment of rotenone in isolated mitochondria caused a significant increase in lipid peroxidation (2.74 fold, 3.62 fold), protein carbonyl contents (2.62 fold, 1.81 fold), and decrease in levels of reduced glutathione (2.02 fold, 1.70 fold) as compared to control. Pre-treatment of curcumin and MTC along with rotenone in the isolated mitochondria significantly reduce the oxidative stress as compared to those treated with rotenone alone. Rotenone treatment in mice significantly increased lipid peroxidation (2.02 fold) and decreased the levels of reduced glutathione (2.99 fold), superoxide dismutase (2.09 fold) and catalase (3.60 fold) in the liver as compared to controls. Co-treatment of curcumin and MTC along with rotenone significantly reduced lipid peroxidation (1.26 fold, 1.76 fold) and increased the levels of reduced glutathione (1.60 fold, 2.43 fold), superoxide dismutase (1.45 fold, 1.99 fold) and catalase (2.32 fold, 2.90 fold) as compared to those treated with rotenone alone. Conclusion The results of the present study indicate that the protective efficacy of MTC against rotenone-induced oxidative damage was more promising than curcumin in both in-vitro and in-vivo system which indicates the enhanced bioavailability of MTC.

Annals of neurosciences, 2018

Lead is widely distributed in the environment and has been found to be associated with various he... more Lead is widely distributed in the environment and has been found to be associated with various health problems including neurodegenerative diseases. In view of the increasing health risk caused by lead, this study has been carried out to investigate the neuroprotective effect of omega-3 fatty acid (omega-3FA) in lead-induced neurotoxicity in rats. Biochemical parameters including oxidative stress in brain regions, lead levels in blood and brain regions and histopathological examination of brain regions of rats were carried out in the present study. Rats exposed to lead (lead acetate 7.5 mg/kg body weight p.o. for 14 days) caused a significant increase in the levels of lipid peroxidation, protein carbonyl content, ROS production and decreased the activities of glutathione peroxidase, superoxide dismutase and catalase in the cerebellum and cerebral cortex, respectively, as compared to controls. Abnormal histopathological changes and increase in the levels of lead in blood and brain we...

Indian journal of clinical biochemistry : IJCB, 2018

The problem of pesticides is not new and its exposure to human due to indiscriminate use is large... more The problem of pesticides is not new and its exposure to human due to indiscriminate use is largely associated with the health related problems including neurotoxicological alterations. High levels of pesticide residues and their metabolites in the dietary constituents, food materials, maternal blood, cord blood, placenta breast milk have been reported and linked to alterations in birth weight, crown heel length, head circumference, mid-arm circumference and ponderal index of the neonates. Epidemiological studies have suggested that exposure of pesticide to human could be a significant risk factor for neurological disorders, including Parkinson's disease, Alzheimer's disease and multiple sclerosis. Cholinergic and non-cholinergic dysfunctions in pesticide exposed population, especially in children have also been frequently reported in recent years. Developmental neurotoxicity is another concern in the area where pregnant are more prone towards its exposure and which results ...

Toxicology and Forensic Medicine - Open Journal, 2016

Alcohol is a depressant drug which slows down the activity of the central nervous system (CNS) an... more Alcohol is a depressant drug which slows down the activity of the central nervous system (CNS) and cause health related problems associated with various positive and negative social experiences. It has both pharmacological and toxic effects on mind and other organs of the human body. In spite of the fact that alcohol is addictive and injurious to health, more than 2 billion chronic alcoholics prevail throughout the world and the number is alarmingly increasing with the addition of new drinkers including teenagers every year. At the same time, young women are found to be more vulnerable towards the adverse consequences of alcohol consumption due to their intrinsic physical differences than men. In recent years, a drinking culture has been socially accepted among the women and it is a matter of great concern among the health scientists. Alcoholism sees as the world's highly prevalent public health problem and therefore it is a serious issue, not confined to any group, culture or country. In view of increasing incidences of alcohol consumption in India and other countries associated with health related and social problems, the present study is carried out to assess the consumption pattern of alcohol in a selected population and try to understand the ill-effects of this social malice on the drinker's social behavior.

SpringerPlus, 2015

Exposure to arsenic in individuals has been found to be associated with immune related problems. ... more Exposure to arsenic in individuals has been found to be associated with immune related problems. In earlier studies, we have demonstrated that amla protects against arsenic induced oxidative stress and apoptosis in thymus and spleen of mice. In continuation to that the present study has therefore been focused to investigate the protective efficacy of amla in arsenic induced inflammation and immunotoxicity in mice. The results showed that arsenic treatment significantly increased serum urea levels (69 %), glucose levels (48 %) and triglyceride levels (66 %) as compared to controls. Mice exposed to arsenic exhibited significant increased in TNF-α (4.3-fold), serum Interleukin-1 beta (threefold), Interleukin-6 (3.8-fold) as compared to controls. Arsenic exposure increased the relative frequency of CD8+ (Tc) cells sub-population (18.9 %) and decreased CD4+ (Th) cells (2.6 %). Arsenic exposure also significantly decreased T (CD3) and B (CD19) cells (21.1 %) as compared to controls. Simultaneously treatment with arsenic and amla significantly inhibited serum urea levels (47 %), glucose levels (50 %) and triglyceride levels (14 %). It also significantly decreased the TNF-α (1.1-fold), levels of IL-1β (1.6-fold), levels of Interleukin-6 (1.3-fold) in serum as compared to those treated with arsenic alone. Simultaneously treatment with arsenic and amla restored the alterations in CD8+ and CD4+ cells and also recovered the damages in B and T sub cells population. Results of the present study clearly indicate that arsenic induced immunotoxicity linked with inflammation has been significantly protected through simultaneous treatment with arsenic and amla that was due to anti-inflammatory and antioxidant activity of amla.

Alzheimer's disease is insidious progressive age related neurological disorder which leads to... more Alzheimer's disease is insidious progressive age related neurological disorder which leads to the loss of cognitive functions, memory processes and associated behavior. The role of environmental factor and genetic susceptibility in the etiology of Alzheimer's disease has been reviewed in recent years. Organophosphates, a class of insecticide are widely used in the agriculture, home, garden, public health programs and therefore associated with the risk of developing Alzheimer's disease in exposed population. Frequent exposure of organophosphates to human populations especially in developing countries has generated insightful concerns among the health scientists about their neurotoxic consequences. The exposure is quite imminent as most of the people are unaware of its toxic insults and handle these chemicals without the safety measures. The exposure may also occur through the consumption of contaminated food products and environmental toxicity. Recent studies suggested th...

Neurotoxicology, Jan 30, 2018

Protective efficacy of curcumin in arsenic induced NMDA receptor dysfunctions and PI3 K/Akt/ GSK3... more Protective efficacy of curcumin in arsenic induced NMDA receptor dysfunctions and PI3 K/Akt/ GSK3β signalling in hippocampus has been investigated in vivo and in vitro. Exposure to sodium arsenite (in vivo - 20 mg/kg, body weight p.o. for 28 days; in vitro - 10 µM for 24 hrs) and curcumin (in vivo - 100 mg/kg body weight p.o. for 28 days; in vitro - 20 µM for 24 hrs) was carried out alone or simultaneously. Treatment with curcumin ameliorated sodium arsenite induced alterations in the levels of NMDA receptors, its receptor subunits and synaptic proteins - pCaMKIIα, PSD-95 and SynGAP both in vivo and in vitro. Decreased levels of BDNF, pAkt, pERK1/2, pGSK3β and pCREB on sodium arsenite exposure were also protected by curcumin. Curcumin was found to decrease sodium arsenite induced changes in hippocampus by modulating PI3 K/Akt/GSK3β neuronal survival pathway, known to regulate various cellular events. Treatment of hippocampal cultures with pharmacological inhibitors for ERK1/2, GSK3β...

Molecular neurobiology, Jan 13, 2016

Earlier, protective role of curcumin in arsenic-induced dopamine (DA)-D2 receptor dysfunctions in... more Earlier, protective role of curcumin in arsenic-induced dopamine (DA)-D2 receptor dysfunctions in corpus striatum has been demonstrated by us. In continuation to that, the present study is focused to decipher the molecular mechanisms associated with alterations in dopaminergic signaling on arsenic exposure in corpus striatum and assess the protective efficacy of curcumin. Exposure to arsenic (20 mg/kg, body weight p.o. for 28 days) in rats resulted to decrease the expression of presynaptic proteins-tyrosine hydroxylase and VMAT2 while no effect was observed on the expression of DAT in comparison to controls. A significant decrease in the expression of DA-D2 receptors associated with alterations in the expression of PKA, pDARPP32 (Thr 34), and PP1 α was clearly evident on arsenic exposure. Expression of BDNF and pGSK3β in corpus striatum was found decreased in arsenic-exposed rats. Simultaneous treatment with curcumin (100 mg/kg, body weight p.o. for 28 days) resulted to protect arse...

Toxicology and industrial health, Jan 8, 2013

Human exposure to monocrotophos, an organophosphate pesticide, could occur due to its high use in... more Human exposure to monocrotophos, an organophosphate pesticide, could occur due to its high use in agriculture to protect crops. Recently, we found that postlactational exposure to monocrotophos impaired cholinergic mechanisms in young rats and such changes persisted even after withdrawal of monocrotophos exposure. In continuation to this, the effect of monocrotophos on noncholinergic targets and role of oxidative stress in its neurotoxicity has been studied. Exposure of rats from postnatal day (PD)22 to PD49 to monocrotophos (0.50 or 1.0 mg kg(-1) body weight, perorally) significantly impaired motor activity and motor coordination on PD50 as compared to controls. A significant decrease in the binding of (3)H-spiperone to striatal membrane (26%, p < 0.01; 30%, p < 0.05) in rats exposed to monocrotophos at both the doses and increase in the binding of (3)H-ketanserin to frontocortical membrane (14%, p > 0.05; 37%, p < 0.05) in those exposed at a higher dose, respectively, ...

Toxicology and Applied Pharmacology, 2014

Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by cu... more Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In contin-22 uation to this, the present study is focused to unravel the molecular mechanisms associated with the protective 23 efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20 mg/kg body weight, p.o) for 24 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dys-25 functions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes 26 and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructur-27 al images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath 28 and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. 29 Simultaneous treatment with arsenic (20 mg/kg body weight, p.o) and curcumin (100 mg/kg body weight, 30 p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential 31 and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of 32 pro-and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following ar-33 senic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the 34 present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expres-35 sion of pro-and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultra-36 structural changes in the brain mitochondria were also protected by curcumin.

International Journal of Developmental Neuroscience, 2014

In view of the increasing incidences of arsenic induced health effects and the vulnerability of t... more In view of the increasing incidences of arsenic induced health effects and the vulnerability of the developing brain to its toxic effects, studies have been carried out to investigate the mechanism of arsenic induced cholinergic alterations and understand if such changes are persistent or transient on withdrawal of arsenic exposure. Male rats were exposed to arsenic (2 mg/kg or 4 mg/kg body weight, p.o) from post-lactational day (PD)22 to PD59, and the effect on selected behavioral and neurochemical end points associated with cholinergic functions was assessed on PD60 and PD90. Decrease in the binding of muscarinic-cholinergic receptors in frontal cortex (26%, 43%) and hippocampus (21%, 34%) associated with reduced CHRM2 mRNA levels, acetylcholinesterase activity and expression of ChAT and PKC ␤-1 was observed in arsenic exposed rats on PD60 as compared to controls. Spatial learning and memory and muscle strength were affected following arsenic exposure in rats on PD60 and associated with arsenic induced cholinergic alterations. Enhanced oxidative stress associated with increased expression of proapoptotic proteins and decreased expression of anti-apoptotic proteins was distinct in both frontal cortex and hippocampus following arsenic exposure in rats on PD60. The cholinergic alterations and other neurochemical modifications were found to be linked with increased arsenic levels in frontal cortex (1.39, 3.90-fold) and hippocampus (3.23, 5.48-fold) on PD60. Although a trend of recovery was observed both in behavioral and neurochemical endpoints on withdrawal of arsenic exposure on PD90, the results indicate that continuous arsenic exposure may have detrimental effects.

International Journal of Developmental Neuroscience, 2014

In view of the increasing incidences of arsenic induced health effects and the vulnerability of t... more In view of the increasing incidences of arsenic induced health effects and the vulnerability of the developing brain to its toxic effects, studies have been carried out to investigate the mechanism of arsenic induced cholinergic alterations and understand if such changes are persistent or transient on withdrawal of arsenic exposure. Male rats were exposed to arsenic (2 mg/kg or 4 mg/kg body weight, p.o) from post-lactational day (PD)22 to PD59, and the effect on selected behavioral and neurochemical end points associated with cholinergic functions was assessed on PD60 and PD90. Decrease in the binding of muscarinic-cholinergic receptors in frontal cortex (26%, 43%) and hippocampus (21%, 34%) associated with reduced CHRM2 mRNA levels, acetylcholinesterase activity and expression of ChAT and PKC ␤-1 was observed in arsenic exposed rats on PD60 as compared to controls. Spatial learning and memory and muscle strength were affected following arsenic exposure in rats on PD60 and associated with arsenic induced cholinergic alterations. Enhanced oxidative stress associated with increased expression of proapoptotic proteins and decreased expression of anti-apoptotic proteins was distinct in both frontal cortex and hippocampus following arsenic exposure in rats on PD60. The cholinergic alterations and other neurochemical modifications were found to be linked with increased arsenic levels in frontal cortex (1.39, 3.90-fold) and hippocampus (3.23, 5.48-fold) on PD60. Although a trend of recovery was observed both in behavioral and neurochemical endpoints on withdrawal of arsenic exposure on PD90, the results indicate that continuous arsenic exposure may have detrimental effects.

Toxicology and Applied Pharmacology, 2009

In view of continued exposure to arsenic and associated human health risk including neurotoxicity... more In view of continued exposure to arsenic and associated human health risk including neurotoxicity, neuroprotective efficacy of curcumin, a polyphenolic antioxidant, has been investigated in rats. A significant decrease in locomotor activity, grip strength (26%) and rota-rod performance (82%) was observed in rats treated with arsenic (sodium arsenite, 20 mg/kg body weight, p.o., 28 days) as compared to controls. The arsenic treated rats also exhibited a decrease in the binding of striatal dopamine receptors (32%) and tyrosine hydroxylase (TH) immunoreactivity (19%) in striatum. Increased arsenic levels in corpus striatum (6.5 fold), frontal cortex (6.3 fold) and hippocampus (7.0 fold) associated with enhanced oxidative stress in these brain regions, as evident by an increase in lipid perioxidation, protein carbonyl and a decrease in the levels of glutathione and activity of superoxide dismutase, catalase and glutathione peroxidase with differential effects were observed in arsenic treated rats compared to controls. Simultaneous treatment with arsenic (sodium arsenite, 20 mg/kg body weight, p.o., 28 days) and curcumin (100 mg/kg body weight, p.o., 28 days) caused an increase in locomotor activity and grip strength and improved the rota-rod performance in comparison to arsenic treated rats. Binding of striatal dopamine receptors and TH expression increased while arsenic levels and oxidative stress decreased in these brain regions in co-treated rats as compared to those treated with arsenic alone. No significant effect on any of these parameters was observed in rats treated with curcumin (100 mg/kg body weight, p.o., 28 days) alone compared to controls. A significant protection in behavioral, neurochemical and immunohistochemical parameters in rats simultaneously treated with arsenic and curcumin suggest the neuroprotective efficacy of curcumin.

Neuroscience Research, 2011

ABSTRACT Human exposure to monocrotophos (MCP) is quite imminent and associated with neurological... more ABSTRACT Human exposure to monocrotophos (MCP) is quite imminent and associated with neurological disorders involving cognitive deficits. In view of increasing human health risk following exposure to MCP, studies have been carried out to investigate the neuroprotective effect of Bacopa monniera (Brahmi) in MCP induced neurobehavioral toxicity in rats. A significant impairment in motor activity and rota-rod performance (64%) associated with decreased binding of dopamine-(D2) receptors in corpus striatum (20%) was observed in rats treated with monocrotophos (1.0 mg/kg body weight, p.o., 28 days) as compared to controls. These rats also exhibited a significant decrease in grip strength (19%) and impaired learning activity (49%) associated with decreased binding of muscarinic-cholinergic receptors (49%) and activity of acetylcholinesterase (48%) in hippocampus as compared to controls. A significant protection in motor activity, rota-rod performance, grip strength (21%) and learning activity (53%) was observed in rats simultaneously treated with monocrotophos and brahmi (50 mg/kg, body weight, p.o., 28 days) as compared to rat treated with MCP alone. Binding of dopamine-(D2) receptor in corpus striatum (22%), muscuranic-cholinergic receptor in hippocampus (28%) and activity of acetylcholinesterase in hippocampus was also found to be increased in rats simultaneously treated with MCP and brahmi as compared to those treated with MCP alone. The results of the present study indicate that treatment with Bacopa monniera significantly modulates the cholinergic and dopaminergic functions and reveal its protective efficacy against MCP induced neurotoxicity in rats.

Human & Experimental Toxicology, 2011

Studies on the neurobehavioral toxicity of monocrotophos, an organophosphate, have been carried o... more Studies on the neurobehavioral toxicity of monocrotophos, an organophosphate, have been carried out on rats following their exposure from postnatal day (PD) 22 to PD 49 to investigate whether neurobehavioral changes are transient or persistent. Exposure of rats to monocrotophos (0.50 or 1.0 mg/kg body weight, p.o.) decreased body weight (10% and 30%) and impaired grip strength (28% and 32%) and learning ability (65% and 68%) at both the doses, respectively in comparison to controls. A trend of recovery was observed in body weight and learning, while decrease in grip strength persisted in rats 15 days after withdrawal. Activity of acetylcholinesterase was decreased in frontal cortex (36% and 67%), hippocampus (21% and 49%) and cerebellum (29% and 51%) in monocrotophos-treated rats at both the doses. The decrease in the activity of acetylcholinesterase persisted in frontal cortex and hippocampus; however, a trend of recovery was observed in cerebellum 15 days after withdrawal. Binding...

The Open Microbiology Journal, 2021

Phylogenetic analysis of different ecosystems has shown that the number of microbial communities ... more Phylogenetic analysis of different ecosystems has shown that the number of microbial communities in a single sample exceeds their cultured counterparts. Microbes have been found throughout nature and can thrive in adverse conditions. Besides inhabiting diverse environments, they also play a key role in the maintenance of the ecosystem. Most of these microbes are either unculturable or difficult to culture with conventional culturing methods. Metagenomics is an emerging field of science that has been in the light for a decade and offers a potential way to assess microbial diversity. The development of metagenomics opens new ways to study genetic material directly from the environmental samples. DNA sequencing and synthesis technologies are making it possible to read and write entire genomes. The huge amount of data obtained from genome sequencing inevitably requires bioinformatics tools to handle and further process them for analysis. Advances in DNA sequencing and high-performance c...

Biomarkers, 2016

In the recent years the uses and applications of pesticides has been tremendously increased and t... more In the recent years the uses and applications of pesticides has been tremendously increased and therefore the risk of exposure to human also increased with adverse health effects including neurotoxicological alterations. Pesticide residues and their metabolites have been detected in dietary constituents, food materials, tissues, maternal blood and breast milk, which are further linked to the developer and neurological disorders. Biomarkers are considered as an important determinant for the examination of organ function, investigation of diseased conditions and therefore could be useful for the analysis procedure. In view of the increasing risk of human health through pesticide exposure, the present review has been focused on the use of biomarkers in pesticide induced biochemical and neurochemical alterations which could help in biomonitoring studies of populations exposed to pesticides along with the main routes of uptake and mechanism of action, which can be used to monitor risk as...

International Journal of Nutrition, Pharmacology, Neurological Diseases, 2018

Introduction: In our earlier studies, we reported that arsenic-induced enhanced oxidative stress,... more Introduction: In our earlier studies, we reported that arsenic-induced enhanced oxidative stress, apoptosis, immunotoxicity and inflammation in the spleen and thymus of mice and hepatotoxicity have been protected through treatment with Emblica officinalis (amla). The present study is focused on to the efficacy of amla in mitigation of arsenic-induced dyslipidemia and alterations in inflammatory biomarkers in the blood of mice. Materials and Methods: Mice were randomly divided into four groups and treated with sodium arsenite (3 mg/kg b.w., per os), amla (500 mg/kg b.w., per os) and simultaneously with arsenic and amla daily for 30 days. Results: Arsenic treatment altered the hematological and lipid profile by increasing total cholesterol (TC), triglyceride (TG), phospholipid (PL) and low-density lipoprotein (LDL) levels and decreasing high-density lipoprotein (HDL) levels as compared to controls. Treatment with arsenic also disturbed the levels of inflammatory biomarkers. Concurrent...

Journal of Biochemical and Molecular Toxicology, 2020

Earlier, we reported that chronic exposure to pesticides causes a reduction in the acetylcholines... more Earlier, we reported that chronic exposure to pesticides causes a reduction in the acetylcholinesterase activity and hematological and biochemical alterations in agriculture workers. In continuation with that, the present study aimed to investigate the pesticide‐induced neurochemical imbalance and its association with behavior alterations in agricultural workers. A significant increase in depressive symptoms, assessed by the Beck Depression Inventory‐II was observed in pesticide exposed workers as compared to the unexposed. A decrease in the level of dopamine in plasma and levels of dopamine, 3,4‐dihydroxyphenylacetic acid, homovanillic acids, norepinephrine, serotonin, and hydroxyindoleacetic acid in urine was also observed. An increase in the levels of MAO‐A and MAO‐B has also been observed in these individuals. The decreased levels of neurotransmitters in the blood and urine have been linked with increased levels of MAO and pesticide residues in plasma and urine. Furthermore, the...

DARU Journal of Pharmaceutical Sciences, 2019

Background Mitochondrial impairments due to free radicals are implicated in a wide range of neuro... more Background Mitochondrial impairments due to free radicals are implicated in a wide range of neurotoxicological alterations. Curcumin, an active ingredient of turmeric has shown protective efficacy against oxidative damage due to its strong antioxidant potential, but its efficiency is restricted due to low bioavailability in the mitochondria. In view of this, we have synthesized mitochondria-targeted curcumin (MTC) with an aim to investigate its efficacy against rotenone-induced oxidative damage in mice and isolated mitochondria. Methods MTC was synthesized by attaching the triphenylphosphonium cation (TPP) as a cationic carrier to the curcumin to assess its protective efficacy in rotenone-induced in-vitro and in-vivo toxicity in mice. Results In-vitro treatment of rotenone in isolated mitochondria caused a significant increase in lipid peroxidation (2.74 fold, 3.62 fold), protein carbonyl contents (2.62 fold, 1.81 fold), and decrease in levels of reduced glutathione (2.02 fold, 1.70 fold) as compared to control. Pre-treatment of curcumin and MTC along with rotenone in the isolated mitochondria significantly reduce the oxidative stress as compared to those treated with rotenone alone. Rotenone treatment in mice significantly increased lipid peroxidation (2.02 fold) and decreased the levels of reduced glutathione (2.99 fold), superoxide dismutase (2.09 fold) and catalase (3.60 fold) in the liver as compared to controls. Co-treatment of curcumin and MTC along with rotenone significantly reduced lipid peroxidation (1.26 fold, 1.76 fold) and increased the levels of reduced glutathione (1.60 fold, 2.43 fold), superoxide dismutase (1.45 fold, 1.99 fold) and catalase (2.32 fold, 2.90 fold) as compared to those treated with rotenone alone. Conclusion The results of the present study indicate that the protective efficacy of MTC against rotenone-induced oxidative damage was more promising than curcumin in both in-vitro and in-vivo system which indicates the enhanced bioavailability of MTC.

Annals of neurosciences, 2018

Lead is widely distributed in the environment and has been found to be associated with various he... more Lead is widely distributed in the environment and has been found to be associated with various health problems including neurodegenerative diseases. In view of the increasing health risk caused by lead, this study has been carried out to investigate the neuroprotective effect of omega-3 fatty acid (omega-3FA) in lead-induced neurotoxicity in rats. Biochemical parameters including oxidative stress in brain regions, lead levels in blood and brain regions and histopathological examination of brain regions of rats were carried out in the present study. Rats exposed to lead (lead acetate 7.5 mg/kg body weight p.o. for 14 days) caused a significant increase in the levels of lipid peroxidation, protein carbonyl content, ROS production and decreased the activities of glutathione peroxidase, superoxide dismutase and catalase in the cerebellum and cerebral cortex, respectively, as compared to controls. Abnormal histopathological changes and increase in the levels of lead in blood and brain we...

Indian journal of clinical biochemistry : IJCB, 2018

The problem of pesticides is not new and its exposure to human due to indiscriminate use is large... more The problem of pesticides is not new and its exposure to human due to indiscriminate use is largely associated with the health related problems including neurotoxicological alterations. High levels of pesticide residues and their metabolites in the dietary constituents, food materials, maternal blood, cord blood, placenta breast milk have been reported and linked to alterations in birth weight, crown heel length, head circumference, mid-arm circumference and ponderal index of the neonates. Epidemiological studies have suggested that exposure of pesticide to human could be a significant risk factor for neurological disorders, including Parkinson's disease, Alzheimer's disease and multiple sclerosis. Cholinergic and non-cholinergic dysfunctions in pesticide exposed population, especially in children have also been frequently reported in recent years. Developmental neurotoxicity is another concern in the area where pregnant are more prone towards its exposure and which results ...

Toxicology and Forensic Medicine - Open Journal, 2016

Alcohol is a depressant drug which slows down the activity of the central nervous system (CNS) an... more Alcohol is a depressant drug which slows down the activity of the central nervous system (CNS) and cause health related problems associated with various positive and negative social experiences. It has both pharmacological and toxic effects on mind and other organs of the human body. In spite of the fact that alcohol is addictive and injurious to health, more than 2 billion chronic alcoholics prevail throughout the world and the number is alarmingly increasing with the addition of new drinkers including teenagers every year. At the same time, young women are found to be more vulnerable towards the adverse consequences of alcohol consumption due to their intrinsic physical differences than men. In recent years, a drinking culture has been socially accepted among the women and it is a matter of great concern among the health scientists. Alcoholism sees as the world's highly prevalent public health problem and therefore it is a serious issue, not confined to any group, culture or country. In view of increasing incidences of alcohol consumption in India and other countries associated with health related and social problems, the present study is carried out to assess the consumption pattern of alcohol in a selected population and try to understand the ill-effects of this social malice on the drinker's social behavior.

SpringerPlus, 2015

Exposure to arsenic in individuals has been found to be associated with immune related problems. ... more Exposure to arsenic in individuals has been found to be associated with immune related problems. In earlier studies, we have demonstrated that amla protects against arsenic induced oxidative stress and apoptosis in thymus and spleen of mice. In continuation to that the present study has therefore been focused to investigate the protective efficacy of amla in arsenic induced inflammation and immunotoxicity in mice. The results showed that arsenic treatment significantly increased serum urea levels (69 %), glucose levels (48 %) and triglyceride levels (66 %) as compared to controls. Mice exposed to arsenic exhibited significant increased in TNF-α (4.3-fold), serum Interleukin-1 beta (threefold), Interleukin-6 (3.8-fold) as compared to controls. Arsenic exposure increased the relative frequency of CD8+ (Tc) cells sub-population (18.9 %) and decreased CD4+ (Th) cells (2.6 %). Arsenic exposure also significantly decreased T (CD3) and B (CD19) cells (21.1 %) as compared to controls. Simultaneously treatment with arsenic and amla significantly inhibited serum urea levels (47 %), glucose levels (50 %) and triglyceride levels (14 %). It also significantly decreased the TNF-α (1.1-fold), levels of IL-1β (1.6-fold), levels of Interleukin-6 (1.3-fold) in serum as compared to those treated with arsenic alone. Simultaneously treatment with arsenic and amla restored the alterations in CD8+ and CD4+ cells and also recovered the damages in B and T sub cells population. Results of the present study clearly indicate that arsenic induced immunotoxicity linked with inflammation has been significantly protected through simultaneous treatment with arsenic and amla that was due to anti-inflammatory and antioxidant activity of amla.

Alzheimer's disease is insidious progressive age related neurological disorder which leads to... more Alzheimer's disease is insidious progressive age related neurological disorder which leads to the loss of cognitive functions, memory processes and associated behavior. The role of environmental factor and genetic susceptibility in the etiology of Alzheimer's disease has been reviewed in recent years. Organophosphates, a class of insecticide are widely used in the agriculture, home, garden, public health programs and therefore associated with the risk of developing Alzheimer's disease in exposed population. Frequent exposure of organophosphates to human populations especially in developing countries has generated insightful concerns among the health scientists about their neurotoxic consequences. The exposure is quite imminent as most of the people are unaware of its toxic insults and handle these chemicals without the safety measures. The exposure may also occur through the consumption of contaminated food products and environmental toxicity. Recent studies suggested th...

Neurotoxicology, Jan 30, 2018

Protective efficacy of curcumin in arsenic induced NMDA receptor dysfunctions and PI3 K/Akt/ GSK3... more Protective efficacy of curcumin in arsenic induced NMDA receptor dysfunctions and PI3 K/Akt/ GSK3β signalling in hippocampus has been investigated in vivo and in vitro. Exposure to sodium arsenite (in vivo - 20 mg/kg, body weight p.o. for 28 days; in vitro - 10 µM for 24 hrs) and curcumin (in vivo - 100 mg/kg body weight p.o. for 28 days; in vitro - 20 µM for 24 hrs) was carried out alone or simultaneously. Treatment with curcumin ameliorated sodium arsenite induced alterations in the levels of NMDA receptors, its receptor subunits and synaptic proteins - pCaMKIIα, PSD-95 and SynGAP both in vivo and in vitro. Decreased levels of BDNF, pAkt, pERK1/2, pGSK3β and pCREB on sodium arsenite exposure were also protected by curcumin. Curcumin was found to decrease sodium arsenite induced changes in hippocampus by modulating PI3 K/Akt/GSK3β neuronal survival pathway, known to regulate various cellular events. Treatment of hippocampal cultures with pharmacological inhibitors for ERK1/2, GSK3β...

Molecular neurobiology, Jan 13, 2016

Earlier, protective role of curcumin in arsenic-induced dopamine (DA)-D2 receptor dysfunctions in... more Earlier, protective role of curcumin in arsenic-induced dopamine (DA)-D2 receptor dysfunctions in corpus striatum has been demonstrated by us. In continuation to that, the present study is focused to decipher the molecular mechanisms associated with alterations in dopaminergic signaling on arsenic exposure in corpus striatum and assess the protective efficacy of curcumin. Exposure to arsenic (20 mg/kg, body weight p.o. for 28 days) in rats resulted to decrease the expression of presynaptic proteins-tyrosine hydroxylase and VMAT2 while no effect was observed on the expression of DAT in comparison to controls. A significant decrease in the expression of DA-D2 receptors associated with alterations in the expression of PKA, pDARPP32 (Thr 34), and PP1 α was clearly evident on arsenic exposure. Expression of BDNF and pGSK3β in corpus striatum was found decreased in arsenic-exposed rats. Simultaneous treatment with curcumin (100 mg/kg, body weight p.o. for 28 days) resulted to protect arse...

Toxicology and industrial health, Jan 8, 2013

Human exposure to monocrotophos, an organophosphate pesticide, could occur due to its high use in... more Human exposure to monocrotophos, an organophosphate pesticide, could occur due to its high use in agriculture to protect crops. Recently, we found that postlactational exposure to monocrotophos impaired cholinergic mechanisms in young rats and such changes persisted even after withdrawal of monocrotophos exposure. In continuation to this, the effect of monocrotophos on noncholinergic targets and role of oxidative stress in its neurotoxicity has been studied. Exposure of rats from postnatal day (PD)22 to PD49 to monocrotophos (0.50 or 1.0 mg kg(-1) body weight, perorally) significantly impaired motor activity and motor coordination on PD50 as compared to controls. A significant decrease in the binding of (3)H-spiperone to striatal membrane (26%, p < 0.01; 30%, p < 0.05) in rats exposed to monocrotophos at both the doses and increase in the binding of (3)H-ketanserin to frontocortical membrane (14%, p > 0.05; 37%, p < 0.05) in those exposed at a higher dose, respectively, ...

Toxicology and Applied Pharmacology, 2014

Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by cu... more Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In contin-22 uation to this, the present study is focused to unravel the molecular mechanisms associated with the protective 23 efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20 mg/kg body weight, p.o) for 24 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dys-25 functions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes 26 and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructur-27 al images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath 28 and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. 29 Simultaneous treatment with arsenic (20 mg/kg body weight, p.o) and curcumin (100 mg/kg body weight, 30 p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential 31 and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of 32 pro-and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following ar-33 senic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the 34 present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expres-35 sion of pro-and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultra-36 structural changes in the brain mitochondria were also protected by curcumin.

International Journal of Developmental Neuroscience, 2014

In view of the increasing incidences of arsenic induced health effects and the vulnerability of t... more In view of the increasing incidences of arsenic induced health effects and the vulnerability of the developing brain to its toxic effects, studies have been carried out to investigate the mechanism of arsenic induced cholinergic alterations and understand if such changes are persistent or transient on withdrawal of arsenic exposure. Male rats were exposed to arsenic (2 mg/kg or 4 mg/kg body weight, p.o) from post-lactational day (PD)22 to PD59, and the effect on selected behavioral and neurochemical end points associated with cholinergic functions was assessed on PD60 and PD90. Decrease in the binding of muscarinic-cholinergic receptors in frontal cortex (26%, 43%) and hippocampus (21%, 34%) associated with reduced CHRM2 mRNA levels, acetylcholinesterase activity and expression of ChAT and PKC ␤-1 was observed in arsenic exposed rats on PD60 as compared to controls. Spatial learning and memory and muscle strength were affected following arsenic exposure in rats on PD60 and associated with arsenic induced cholinergic alterations. Enhanced oxidative stress associated with increased expression of proapoptotic proteins and decreased expression of anti-apoptotic proteins was distinct in both frontal cortex and hippocampus following arsenic exposure in rats on PD60. The cholinergic alterations and other neurochemical modifications were found to be linked with increased arsenic levels in frontal cortex (1.39, 3.90-fold) and hippocampus (3.23, 5.48-fold) on PD60. Although a trend of recovery was observed both in behavioral and neurochemical endpoints on withdrawal of arsenic exposure on PD90, the results indicate that continuous arsenic exposure may have detrimental effects.

International Journal of Developmental Neuroscience, 2014

In view of the increasing incidences of arsenic induced health effects and the vulnerability of t... more In view of the increasing incidences of arsenic induced health effects and the vulnerability of the developing brain to its toxic effects, studies have been carried out to investigate the mechanism of arsenic induced cholinergic alterations and understand if such changes are persistent or transient on withdrawal of arsenic exposure. Male rats were exposed to arsenic (2 mg/kg or 4 mg/kg body weight, p.o) from post-lactational day (PD)22 to PD59, and the effect on selected behavioral and neurochemical end points associated with cholinergic functions was assessed on PD60 and PD90. Decrease in the binding of muscarinic-cholinergic receptors in frontal cortex (26%, 43%) and hippocampus (21%, 34%) associated with reduced CHRM2 mRNA levels, acetylcholinesterase activity and expression of ChAT and PKC ␤-1 was observed in arsenic exposed rats on PD60 as compared to controls. Spatial learning and memory and muscle strength were affected following arsenic exposure in rats on PD60 and associated with arsenic induced cholinergic alterations. Enhanced oxidative stress associated with increased expression of proapoptotic proteins and decreased expression of anti-apoptotic proteins was distinct in both frontal cortex and hippocampus following arsenic exposure in rats on PD60. The cholinergic alterations and other neurochemical modifications were found to be linked with increased arsenic levels in frontal cortex (1.39, 3.90-fold) and hippocampus (3.23, 5.48-fold) on PD60. Although a trend of recovery was observed both in behavioral and neurochemical endpoints on withdrawal of arsenic exposure on PD90, the results indicate that continuous arsenic exposure may have detrimental effects.

Toxicology and Applied Pharmacology, 2009

In view of continued exposure to arsenic and associated human health risk including neurotoxicity... more In view of continued exposure to arsenic and associated human health risk including neurotoxicity, neuroprotective efficacy of curcumin, a polyphenolic antioxidant, has been investigated in rats. A significant decrease in locomotor activity, grip strength (26%) and rota-rod performance (82%) was observed in rats treated with arsenic (sodium arsenite, 20 mg/kg body weight, p.o., 28 days) as compared to controls. The arsenic treated rats also exhibited a decrease in the binding of striatal dopamine receptors (32%) and tyrosine hydroxylase (TH) immunoreactivity (19%) in striatum. Increased arsenic levels in corpus striatum (6.5 fold), frontal cortex (6.3 fold) and hippocampus (7.0 fold) associated with enhanced oxidative stress in these brain regions, as evident by an increase in lipid perioxidation, protein carbonyl and a decrease in the levels of glutathione and activity of superoxide dismutase, catalase and glutathione peroxidase with differential effects were observed in arsenic treated rats compared to controls. Simultaneous treatment with arsenic (sodium arsenite, 20 mg/kg body weight, p.o., 28 days) and curcumin (100 mg/kg body weight, p.o., 28 days) caused an increase in locomotor activity and grip strength and improved the rota-rod performance in comparison to arsenic treated rats. Binding of striatal dopamine receptors and TH expression increased while arsenic levels and oxidative stress decreased in these brain regions in co-treated rats as compared to those treated with arsenic alone. No significant effect on any of these parameters was observed in rats treated with curcumin (100 mg/kg body weight, p.o., 28 days) alone compared to controls. A significant protection in behavioral, neurochemical and immunohistochemical parameters in rats simultaneously treated with arsenic and curcumin suggest the neuroprotective efficacy of curcumin.

Neuroscience Research, 2011

ABSTRACT Human exposure to monocrotophos (MCP) is quite imminent and associated with neurological... more ABSTRACT Human exposure to monocrotophos (MCP) is quite imminent and associated with neurological disorders involving cognitive deficits. In view of increasing human health risk following exposure to MCP, studies have been carried out to investigate the neuroprotective effect of Bacopa monniera (Brahmi) in MCP induced neurobehavioral toxicity in rats. A significant impairment in motor activity and rota-rod performance (64%) associated with decreased binding of dopamine-(D2) receptors in corpus striatum (20%) was observed in rats treated with monocrotophos (1.0 mg/kg body weight, p.o., 28 days) as compared to controls. These rats also exhibited a significant decrease in grip strength (19%) and impaired learning activity (49%) associated with decreased binding of muscarinic-cholinergic receptors (49%) and activity of acetylcholinesterase (48%) in hippocampus as compared to controls. A significant protection in motor activity, rota-rod performance, grip strength (21%) and learning activity (53%) was observed in rats simultaneously treated with monocrotophos and brahmi (50 mg/kg, body weight, p.o., 28 days) as compared to rat treated with MCP alone. Binding of dopamine-(D2) receptor in corpus striatum (22%), muscuranic-cholinergic receptor in hippocampus (28%) and activity of acetylcholinesterase in hippocampus was also found to be increased in rats simultaneously treated with MCP and brahmi as compared to those treated with MCP alone. The results of the present study indicate that treatment with Bacopa monniera significantly modulates the cholinergic and dopaminergic functions and reveal its protective efficacy against MCP induced neurotoxicity in rats.

Human & Experimental Toxicology, 2011

Studies on the neurobehavioral toxicity of monocrotophos, an organophosphate, have been carried o... more Studies on the neurobehavioral toxicity of monocrotophos, an organophosphate, have been carried out on rats following their exposure from postnatal day (PD) 22 to PD 49 to investigate whether neurobehavioral changes are transient or persistent. Exposure of rats to monocrotophos (0.50 or 1.0 mg/kg body weight, p.o.) decreased body weight (10% and 30%) and impaired grip strength (28% and 32%) and learning ability (65% and 68%) at both the doses, respectively in comparison to controls. A trend of recovery was observed in body weight and learning, while decrease in grip strength persisted in rats 15 days after withdrawal. Activity of acetylcholinesterase was decreased in frontal cortex (36% and 67%), hippocampus (21% and 49%) and cerebellum (29% and 51%) in monocrotophos-treated rats at both the doses. The decrease in the activity of acetylcholinesterase persisted in frontal cortex and hippocampus; however, a trend of recovery was observed in cerebellum 15 days after withdrawal. Binding...