Omid Farshad - Profile on Academia.edu (original) (raw)

Papers by Omid Farshad

DARU, Jan 22, 2014

Purpose of the study: Comparative in vitro studies were carried out to determine the adsorption c... more Purpose of the study: Comparative in vitro studies were carried out to determine the adsorption characteristics of 3 drugs on activated charcoal (AC) and sodium polystyrene sulfonate (SPS). Activated charcoal (AC) has been long used as gastric decontamination agent for tricyclic antidepressants (TCA). Methods: Solutions containing drugs (amitriptyline, clomipramine, or doxepin) and variable amount of AC or SPS were incubated for 30 minutes. Results: At pH 1.2 the adsorbent: drug mass ratio varied from 2 : 1 to 40 : 1 for AC, and from 0.4 : 1 to 8 : 1 for SPS. UV-VIS spectrophotometer was used for the determination of free drug concentrations. The qmax of amitriptyline was 0.055 mg/mg AC and 0.574 mg/mg SPS, qmax of clomipramine was 0.053 mg/mg AC and 0.572 mg/mg SPS, and qmax of doxepin was 0.045 mg/mg AC and 0.556 mg/mg SPS. The results of adsorption experiments with SPS revealed higher values for the qmax parameters in comparison with AC. Conclusion: In vitro gastric decontamination experiments for antidepressant amitriptyline, clomipramine, and doxepin showed that SPS has higher qmax values than the corresponding experiments with AC. Therefore, we suggest SPS is a better gastric decontaminating agent for the management of acute TCA intoxication.

Journal of Renal and Hepatic Disorders, Jun 9, 2020

Manganese (Mn) is an essential element that is incorporated in various metabolic pathways and enz... more Manganese (Mn) is an essential element that is incorporated in various metabolic pathways and enzyme structures. On the other hand, a range of adverse effects has been described in association with Mn overexposure. Mn is a well-known neurotoxic agent in mammals. Renal injury is another adverse effect associated with Mn intoxication. No precise mechanism for Mn nephrotoxicity has been identified so far. The current study was designed to evaluate the potential mechanisms of Mn-induced renal injury. Rats were treated with Mn (20 and 40 mg/mL, respectively, in drinking water) for 30 consecutive days. Markers of oxidative stress, as well as several mitochondrial indices, were assessed in the kidney tissue. Renal injury was evident in Mn-treated animals, as judged by a significant increase in serum BUN and creatinine. Moreover, urinalysis revealed a significant increase in urine glucose, phosphate, and protein in Mn-treated rats. Kidney histopathological alterations, including tubular atrophy, interstitial inflammation, and necrosis, were also detected in Mn-treated animals. Biomarkers of oxidative stress, including an increment in reactive oxygen species (ROS), lipid peroxidation, and oxidized glutathione (GSSG), were detected in Mn-treated groups. On the other hand, kidney glutathione (GSH) stores and total antioxidant capacity were depleted in Mn groups. Mn exposure was associated with significant mitochondrial depolarization, decreased mitochondrial dehydrogenases activity, mitochondrial permeabilization, and depletion of adenosine tri-phosphate (ATP) content. These data highlight oxidative stress and mitochondrial impairment as potential mechanisms involved in Mn-induced renal injury.

Apoptosis-inducing factor plays a role in the pathogenesis of hepatic and renal injury during cholestasis

Naunyn-Schmiedeberg's Archives of Pharmacology

Cholestasis is a clinical complication with different etiologies. The liver is the primary organ ... more Cholestasis is a clinical complication with different etiologies. The liver is the primary organ influenced in cholestasis. Renal injury is also a severe clinical complication in cholestatic/cirrhotic patients. Several studies mentioned the importance of oxidative stress and mitochondrial impairment as two mechanistically interrelated events in cholestasis-induced organ injury. Apoptosis-inducing factor (AIF) is a flavoprotein located in the inner mitochondrial membrane. This molecule is involved in a distinct pathway of cell death. The current study aimed to evaluate the role of AIF in the pathophysiology of cholestasis-associated hepatic and renal injury. Bile duct ligation (BDL) was used as an animal model of cholestasis. Serum, urine, and tissue samples were collected at scheduled time intervals (3, 7, 14, and 28 days after BDL surgery). Tissues' AIF mRNA levels, as well as serum, urine, and tissue activity of AIF, were measured. Moreover, markers of DNA fragmentation and apoptosis were assessed in the liver and kidney of cholestatic animals. A significant increase in liver and kidney AIF mRNA levels, in addition to increased AIF activity in the liver, kidney, serum, and urine, was detected in BDL rats. DNA fragmentation and apoptosis were raised in the liver and kidney of cholestatic animals, especially at the early stage of the disease. The apoptotic mode of cell death in the liver and kidney was connected to a higher AIF level. These data mention the importance of AIF in the pathogenesis of cholestasis-induced organ injury, especially at the early stage of this disease. Mitochondrial release of apoptosis-inducing factor (AIF) seems to play a pathogenic role in cholestasis-associated hepatic and renal injury. AIF release is directly connected to oxidative stress and mitochondrial impairment in cholestatic animals.

Protective effects of different extracts and essential oil from Pimpinella anisum L. seeds were e... more Protective effects of different extracts and essential oil from Pimpinella anisum L. seeds were examined against carbon tetrachloride (CCl4)-induced toxicity. The parameters such as serum transaminases, lactate dehydrogenase activity, hepatic glutathione content, liver lipid peroxidation and histopathological changes of liver were assessed as toxicity markers. In the in vitro model of this study, markers such as cell viability, cellular reduced and oxidized glutathione and lipid peroxidation in HepG2 cells were evaluated. Materials and Methods: Human liver cancer cell line HepG2 and male Sprague-Dawley rats were treated with extracts and essential oil, and markers of hepatotoxicity were investigated. The data revealed that the n-hexane extract, effectively attenuated CCl4-induced toxicity in both in vitro and in vivo models in current investigation. As the oxidative stress markers were ameliorated, it might be concluded that anise seed possesses protective effects probably due to its antioxidant constituents.

Pharmaceutical Sciences, 2020

Background: Cholestatic liver disease primarily affects hepatic tissue. Cholestasis could also in... more Background: Cholestatic liver disease primarily affects hepatic tissue. Cholestasis could also influence the function of other organs rather than the liver. Cholestasis-induced kidney injury is a severe clinical complication known as "cholemic nephropathy" (CN). Bile duct ligation (BDL) is a trustworthy experimental model for inducing CN. Although the precise mechanism of renal injury in cholestasis is not fully recognized, several studies revealed the role of oxidative stress in CN. There is no promising pharmacological intervention against CN. Carnosine (CAR) is a peptide extensively investigated for its pharmacological effects. Radical scavenging and antioxidative stress are major features of CAR. The current study aimed to evaluate the role of CAR supplementation on the CN. Methods: CAR was administered (250 and 500 mg/kg, i.p) to BDL rats for 14 consecutive days. Urine and serum markers of renal injury, biomarkers of oxidative stress in the kidney tissue, and renal hi...

Frontiers in Veterinary Science, 2020

Carbon-based nanomaterials possess a remarkably high potential for biomedical applications due to... more Carbon-based nanomaterials possess a remarkably high potential for biomedical applications due to their physical properties; however, their detrimental effects on reproduction are also concerned. Several reports indicate the toxicity of carbon nanotubes (CNT); nevertheless, their impact on intracellular organelles in the male reproductive organs has not been fully elucidated. Herein, we report on the reprotoxicity of single-walled (SWCNT) and multi-walled carbon nanotubes (MWCN) on several intracellular events and histological criteria in pubertal male BALB/c mice orally treated with 0, 10, and 50 mg/kg/day doses for 5 weeks. Biomarkers of oxidative stress and mitochondrial functionality, histopathological alterations, and epididymal sperm characteristics were determined. Oral administration of CNTs at 10 and 50 mg/kg evoked a significant decrement in weight coefficient, sperm viability and motility, hypo-osmotic swelling (HOS) test, sperm count, mitochondrial dehydrogenase activity...

Iranian Journal of Basic Medical Sciences, 2015

Objective(s): Protective effects of different extracts and essential oil from Pimpinella anisum L... more Objective(s): Protective effects of different extracts and essential oil from Pimpinella anisum L. seeds were examined against carbon tetrachloride (CCl4)-induced toxicity. The parameters such as serum transaminases, lactate dehydrogenase activity, hepatic glutathione content, liver lipid peroxidation and histopathological changes of liver were assessed as toxicity markers. In the in vitro model of this study, markers such as cell viability, cellular reduced and oxidized glutathione and lipid peroxidation in HepG2 cells were evaluated. Materials and Methods: Human liver cancer cell line HepG2 and male Sprague-Dawley rats were treated with extracts and essential oil, and markers of hepatotoxicity were investigated. Results: The data revealed that the n-hexane extract, effectively attenuated CCl4-induced toxicity in both in vitro and in vivo models in current investigation. Conclusion: As the oxidative stress markers were ameliorated, it might be concluded that anise seed possesses pr...

Taurine (TAU) is the most abundant free amino acid in the human body. High concentrations of this... more Taurine (TAU) is the most abundant free amino acid in the human body. High concentrations of this amino acid are found in tissues such as the skeletal muscle, brain, and kidney. Recently, a focus has emerged on the effects of TAU on cellular mitochondria. It has been found that TAU could positively affect this organelle by enhancing mitochondrial membrane potential, increasing ATP levels, and mitigating mitochondria-mediated ROS formation. The current study aimed to evaluate the effect of a wide range of TAU concentrations (0.01 mM-1000 mM) on mitochondrial function. Mice liver mitochondria were isolated and exposed to different concentrations of TAU (30 min). Several indices, including mitochondrial depolarization, dehydrogenases activity, permeabilization, and ATP content, were monitored. It was found that TAU supplementation significantly enhanced parameters such as mitochondrial ATP levels and mitochondrial membrane potential in comparison with the control group. Moreover, TAU p...

The xenobiotics-induced liver injury is a major clinical complication. Hence, finding hepatoprote... more The xenobiotics-induced liver injury is a major clinical complication. Hence, finding hepatoprotective agents could have clinical value. Herbal medicines are a major source of biologically active chemicals which could be applied as hepatoprotective agents. The current study was designed to assess the hepatoprotective properties of Avicennia Marina (AM) extract and its different fractions. In vivo, the hepatoprotective effect of AM total extract against CCl 4 -induced acute liver injury was evaluated in rats, and a series of histopathological, biochemical, and oxidative stress parameters were monitored. In vitro, the protective effect of AM extract fractions (Petroleum ether, Chloroform, Ethyl acetate, and Ethanol) was evaluated on human liver hepatoma cells (HepG2). Severe elevation in serum level of liver injury biomarkers, along with liver tissue histopathological changes, lipid peroxidation, and liver tissue glutathione depletion were detected in CCl 4 -treated rats. On the other...

Journal of Chemistry, 2021

Objective. Manganese (Mn) has been reported, through dietary and occupational overexposure, to in... more Objective. Manganese (Mn) has been reported, through dietary and occupational overexposure, to induce neurotoxicity named manganism. Pentoxifylline (PTX) administration attracts much attention considering the beneficial properties of PTX, as an anti-inflammatory and smooth muscle relaxation agent. This in vivo study aims to evaluate the effect of PTX on manganism in rat model. Materials and Methods. Thirty adult male Sprague Dawley rats received MnCl2 (100 mg/kg, i.p. on days 1, 3, and 7) during a week alone or in combination with PTX (300 mg/kg, i.p. every day for 8 consecutive days on manganism rat model). Several locomotor activity indices, as well as biomarkers of oxidative stress, were monitored in the brain tissue of Mn-exposed animals. Results. It was found that PTX supplementation (300 mg/kg, i.p.) deteriorated the Mn-induced locomotor deficit. This drug also increased the Mn brain accumulation as well as reactive oxygen species (ROS) and lipid peroxidation products in the m...

Biologia, 2020

Cholestasis-associated renal injury, known as cholemic nephropathy (CN), is a severe clinical com... more Cholestasis-associated renal injury, known as cholemic nephropathy (CN), is a severe clinical complication. CN could lead to acute kidney injury. However, there is no specific pharmacological intervention for cholestasis-induced renal injury. Oxidative stress and mitochondrial impairment seem to play a role in the pathogenesis of CN. Betaine (3-methyl glycine; BET) is an amino acid derivative with a wide range of pharmacological actions. Several studies mentioned the effects of BET on oxidative stress in different experimental models. It has also been found that BET positively affected mitochondrial function. The current study aimed to evaluate the effects of BET supplementation on CN in the bile duct ligation (BDL) model of cholestasis. BET (0.25% and 1% w: v in drinking water) was administered to BDL animals for seven consecutive days. Biomarkers of oxidative stress and mitochondrial indices were evaluated in cholestatic animals. Significant elevation in reactive oxygen species formation, lipid peroxidation, and oxidized glutathione (GSSG) was evident in BDL rats. Moreover, reduced glutathione (GSH) levels and renal antioxidant capacity were decreased in cholestatic animals. Mitochondrial depolarization, mitochondrial permeabilization, decreased mitochondrial dehydrogenases activity, and lipid peroxidation was also detected in the kidney of BDL rats. Tubular atrophy, interstitial inflammation, and renal fibrosis were also detected in BDL rats. BET alleviated biomarkers of oxidative stress, improved mitochondrial indices, and decreased renal histopathological alterations in BDL animals. The antioxidant effects and the positive effects of BET on cellular mitochondria seem to play a fundamental role in its nephroprotective role during cholestasis.

Journal of Experimental Pharmacology, 2020

Purpose: Hepatic encephalopathy (HE) is described as impaired brain function induced by liver fai... more Purpose: Hepatic encephalopathy (HE) is described as impaired brain function induced by liver failure. Ammonia is the most suspected chemical involved in brain injury during HE. Although the precise mechanism of HE is not clear, several studies mentioned the role of oxidative stress in ammonia neurotoxicity. In animal models, the use of some compounds with antioxidant properties was reported to reduce the neurotoxic effects of ammonia, improve energy metabolism, and ameliorate the HE symptoms. Citicoline is a principal intermediate in the biosynthesis pathway of phosphatidylcholine that acts as neurovascular protection and repair effects. Various studies mentioned the neuroprotective and antioxidative effects of citicoline in the central nervous system. This study aims to investigate the potential protective effects of citicoline therapeutic in an animal model of HE. Materials and Methods: Mice received acetaminophen (APAP,1g/kg, i. p.) and then treated with citicoline (500 mg/kg, i.p) one and two hours after APAP. Animals were monitored for locomotor activity and blood and brain ammonia levels. Moreover, markers of oxidative stress were assessed in the brain tissue. The result of the study revealed that plasma and brain ammonia and the liver injury markers increased, and locomotor activity impaired in the APAP-treated animals. Besides, an increase in markers of oxidative stress was evident in the brain of the APAP-treated mice. It was found that citicoline supplementation enhanced the animal's locomotor activity and improved brain tissue markers of oxidative stress. Conclusion: These data propose citicoline as a potential protective agent in HE. The effects of citicoline on oxidative stress markers could play a fundamental role in its neuroprotective properties during HE.

Veterinary Medicine and Science, 2020

The ovariectomized rat is a widely used preclinical model for studying postmenopausal and its com... more The ovariectomized rat is a widely used preclinical model for studying postmenopausal and its complications. In this study, the therapeutic effect of flaxseed oil on the ovariectomized adult rats was investigated. Our results showed that biochemical parameters including calcium, oestrogen and progesterone levels increase 8 weeks after ovariectomy in rats. Also, the amount of alkaline phosphatase decreased significantly after 8 weeks compared with the OVX rat. The healing potential of flaxseed oil was proven by successfully recovering the affected tissue and preventing the unpleasant symptoms of ovariectomized rats. The biological effects of flaxseed oil may be due to high amounts of fatty acids, phytoestrogens and an array of antioxidants. The results suggest that flaxseed oil can mimic the action of oestrogen and can be a potential treatment for hormone replacement therapy (HRT).

Metformin alleviates cholestasis-associated nephropathy through regulating oxidative stress and mitochondrial function

Liver Research, 2020

Abstract Background and aim Cholestasis-associated renal injury or cholemic nephropathy (CN) is a... more Abstract Background and aim Cholestasis-associated renal injury or cholemic nephropathy (CN) is a serious clinical problem. Previous studies mentioned that oxidative stress and mitochondrial impairment play a role in CN. There is no specific pharmacological intervention for CN. Metformin is an anti-diabetic drug administered for decades. On the other hand, novel pharmacological properties have emerged for this drug. The effect of metformin on oxidative stress parameters has been well-recognized in different experimental models. It has also been found that metformin positively affected mitochondrial function. The current study aimed to evaluate the effects of metformin in an animal model of CN. Methods Rats underwent bile duct ligation (BDL) and were treated with metformin (250 and 500 mg/kg) for 14 consecutive days. Two weeks after the BDL operations, urine, serum, and kidney samples were collected and analyzed. Results Markers of oxidative stress, including reactive oxygen species (ROS) formation, lipid peroxidation, protein carbonylation, depleted antioxidant capacity, and decreased glutathione (GSH) levels were detected in BDL animals. Moreover, mitochondrial indices, including adenosine triphosphate (ATP) level, dehydrogenase activity, mitochondrial membrane potential, and mitochondrial permeability, were impaired in the kidney of cholestatic rats. Renal histopathological alterations in cholestatic animals included tubular degeneration and interstitial inflammation, cast formation, and fibrosis. It was found that metformin significantly alleviated oxidative stress and improved mitochondrial indices in the kidney of cholestatic rats. Tissue histopathological alterations were also mitigated in metformin-treated groups. Conclusions Metformin could be a candidate for managing CN. The nephroprotective role of metformin is primarily associated with its effects on oxidative stress parameters and mitochondrial function.

Biological Trace Element Research, 2020

Lithium is abundantly administered against bipolar disorder. On the other hand, the lithium-induc... more Lithium is abundantly administered against bipolar disorder. On the other hand, the lithium-induced renal injury is a clinical complication which commonly reveals as drug-induced diabetes insipidus. However, lithium-induced cytotoxicity might also play a role in the adverse effects of this drug on the kidney. There is no clear cellular and molecular mechanism(s) for lithiuminduced nephrotoxicity. The current study was designed to assess the effect of lithium on kidney tissue oxidative stress biomarkers and mitochondrial function and its relevance to drug-induced nephrotoxicity and electrolyte imbalance. Rats were treated with lithium (lithium carbonate, 25 and 50 mg/kg/day, i.p., for 28 consecutive days). Kidney mitochondria were also isolated from rats and exposed to increasing concentrations of lithium (0.01-10 mM). Serum and urine biomarkers of kidney injury, kidney tissue markers of oxidative stress, and renal histopathological changes were assessed. Moreover, several mitochondrial indices were monitored. Lithium-induced renal injury revealed a significant increase in urine and serum biomarkers of renal impairment. Lithium caused an increase in the kidney reactive oxygen species (ROS) level and lipid peroxidation (LPO). Renal glutathione (GSH) reservoirs were also depleted, and tissue antioxidant capacity decreased in lithium-treated animals. Significant tissue histopathological changes, including necrosis, Bowman capsule dilation, and interstitial inflammation, were evident in lithium-treated animals. On the other hand, significant alterations in kidney mitochondrial function were detected in lithium-treated groups. These data mention oxidative stress, mitochondrial dysfunction, and cellular energy crisis as the potential primary mechanisms for lithium-induced renal injury.

Current Research in Pharmacology and Drug Discovery, 2020

It has been well documented that cirrhosis is associated with the intestinal injury. Intestinal i... more It has been well documented that cirrhosis is associated with the intestinal injury. Intestinal injury in cirrhosis could lead to bacterial lipopolysaccharide (LPS) translocation to the systemic circulation. It has been found that high plasma LPS is connected with higher morbidity and mortality in cirrhotic patients. Therefore, finding therapeutic approaches to mitigate this complication has great clinical value. Several investigations mentioned the pivotal role of oxidative stress in cirrhosis-associated intestinal injury. It has been well-known that the redox balance of enterocytes is disturbed in cirrhotic patients. In the current study, the effects of thiol-reducing agents N-acetylcysteine (NAC) (0.5 and 1% w: v) and dithiothreitol (DTT) (0.5 and 1% w: v) on biomarkers of oxidative stress, tissue histopathological alterations, and LPS translocation is investigated in a rat model of cirrhosis. Bile duct ligation (BDL) surgery was used to induce cirrhosis in male Sprague-Dawley rats. Animals (n ¼ 48; 8 animals/group) were supplemented with NAC and DTT for 28 consecutive days. Significant changes in ileum and colon markers of oxidative stress were evident in BDL rats as judged by increased reactive oxygen species (ROS), lipid peroxidation, oxidized glutathione (GSSG), and protein carbonylation along with decreased antioxidant capacity and glutathione (GSH) content. Blunted villus, decreased villus number, and inflammation was also detected in the intestine of BDL animals. Moreover, serum LPS level was also significantly higher in BDL rats. NAC and DTT administration (0.5 and 1% w: v, gavage) significantly decreased biomarkers of oxidative stress, mitigated intestinal histopathological alterations, and restored tissue antioxidant capacity. Moreover, NAC and/or DTT significantly suppressed LPS translocation to the systemic circulation. The protective effects of thiol reducing agents in the intestine of cirrhotic rats could be attributed to the effect of these chemicals on the cellular redox environment and biomarkers of oxidative stress.

Journal of Renal and Hepatic Disorders, 2020

PharmaNutrition, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

The Nephroprotective Role of Carnosine Against Ifosfamide-Induced Renal Injury and Electrolytes Imbalance is Mediated Via the Regulation of Mitochondrial Function and Alleviation of Oxidative Stress

Drug Research, 2019

Background Ifosfamide (IFO) is an alkylating agent administered against different types of malign... more Background Ifosfamide (IFO) is an alkylating agent administered against different types of malignancies. Several cases of renal injury and serum electrolytes disturbances have been reported in IFO-treated patients. Oxidative stress and mitochondrial dysfunction are suspected of being involved in the mechanism of IFO nephrotoxicity. Carnosine is a dipeptide which its antioxidant and mitochondria protecting properties have been mentioned in different experimental models. The current study aimed to evaluate the nephroprotective properties of carnosine against IFO-induced renal injury. Methods Rats were treated with IFO (50 mg/kg, i.p) alone or in combination with carnosine. Serum and urine biomarkers of renal injury in addition to kidney markers of oxidative stress were evaluated. Moreover, kidney mitochondria were isolated, and some mitochondrial indices were assessed. Results Elevated serum creatinine and BUN, hypokalemia, and hypophosphatemia, in addition, to an increase in urine gl...

Toxicology Letters, 2019

Cholestasis and accumulation of cytotoxic molecules (e.g., hydrophobic bile acids) are connected ... more Cholestasis and accumulation of cytotoxic molecules (e.g., hydrophobic bile acids) are connected to a wide range of organ injury. Reproductive organs in both males and females could be affected by cholestasis. The data collected in the current study represent severe oxidative stress and mitochondrial impairment as fundamental mechanisms of cholestasis-associated reproductive toxicity.