Mahmoud ghazi-Khansari - Academia.edu (original) (raw)

Papers by Mahmoud ghazi-Khansari

BMC Pharmacology and Toxicology

Background Doxorubicin (DOX) is an effective antitumor agent, but its clinical usage is limited d... more Background Doxorubicin (DOX) is an effective antitumor agent, but its clinical usage is limited due to adverse cardiotoxic effects. Several compounds have been studied to reduce DOX cardiotoxicity to improve its therapeutic index. This study was aimed to investigate the protective effects of sodium thiosulfate (STS) pre-treatment against DOX-induced cardiomyopathy in rats. Methods Male Wistar rats were randomized into 4 groups: control (saline), DOX (2.5 mg/kg, 3 times per week, intraperitoneal [i.p.]), STS (300 mg/kg, 3 times per week, i.p), and DOX + STS (30 min prior to DOX injection, 3 times per week, i.p.) over a period of 2 weeks. The body weight, electrocardiography, histopathology, papillary muscle contractility, and oxidative stress biomarkers in heart tissues were assessed. Results The results indicated that STS significantly improved the body weight (P < 0.01), decreased QRS complex and QT interval on ECG (P < 0.05 and P < 0.001, respectively), as well as decline...

Drug Metabolism and Drug Interactions

Objectives Due to lack of adequate data on tramadol kinetic in relevance of CYP2D6 toxicity, this... more Objectives Due to lack of adequate data on tramadol kinetic in relevance of CYP2D6 toxicity, this study was designed to investigate the effect of CYP2D6 phenotype in tramadol poisoning. The saliva, urine and blood samples were taken at the admission time. Consequently, concentration of tramadol and its major metabolites were measured. Methods A pharmacokinetic and metabolic study was developed in cases of tramadol poisoned (n=96). Cases of tramadol poisoned evidenced seizure, hypertension, dizziness, nausea and vomiting symptoms participated. Results Female cases showed higher N-desmethyltramadol (M2) tramadol concentrations than male cases: in urine (40.12 ± 124.53 vs. 7.3 ± 7.13), saliva (16.91 ± 26.03 vs. 5.89 ± 7.02), and blood (1.11 ± 1.56 vs. 0.3 ± 0.38) samples. Significant correlation between blood, saliva, and urine concentrations were found (r = 0.5). Based on the metabolic ratio of O-desmethyltramadol (M1) of male (0.53 ± 0.22) and female (0.43 ± 0.26), poisoning and seve...

ACTA MEDICA IRANICA, 2021

Malathion is an organophosphorus insecticide widely used in agriculture, residential area, and pu... more Malathion is an organophosphorus insecticide widely used in agriculture, residential area, and public health programs with a known mechanism of toxicity of inhibition of acetylcholinesterase and induction of oxidative stress. Gold nanoparticles (AuNPs) represent stable and easily synthesized nanoparticles with extensive use in consumer products and medicine. Due to the antioxidant property of AuNPs, it is possible that AuNPs may prevent malathion-induced oxidative damage. In this study, the cytotoxicity of malathion and AuNPs (10 and 20 nm) were measured separately in Caco-2 cells. Then the protective effects of AuNPs were evaluated by measuring the oxidative stress (lipid peroxidation level and glutathione content) and acetylcholinesterase activity. The calculated IC50s values at 48 hr were 326.8±0.32, 43.09±0.65, and 41.46±0.24 µg/ml for malathion, AuNPs 10 and 20 nm, respectively. Then, the lowest concentration of AuNPs (1 µg/ml) and IC50 concentration of malathion (326.8 µg/ml) ...

Psychopharmacology, 2021

RATIONALE Major depressive disorder (MDD) is a debilitating disorder with adverse effects on mood... more RATIONALE Major depressive disorder (MDD) is a debilitating disorder with adverse effects on mood, memory, and quality of life. OBJECTIVES In this study, the antidepressant potential of glatiramer acetate (GA), a drug used in the management of multiple sclerosis, was investigated in acute and chronic models of depression in male mice. The acute antidepressant screening was performed with the forced swim (FST) and tail suspension (TST) tests. In the chronic phase, post-weaning social isolation (SI) was used to induce depressive-/anxiety-like behaviors. METHODS Mice were reared in two different groups of social (SG) and isolated (IG) for 4 weeks. IG mice were treated with 0.5, 1.0, and 2.0 mg/kg of GA for the last 2 weeks of the SI period. Animals were assessed by the behavioral tests of depression, anxiety, learning, and memory, and hippocampal brain-derived neurotrophic factor (BDNF) level was measured. RESULTS The acute tests confirmed the antidepressant potential of GA. In the chronic phase, GA could reduce immobility time in FST (P < 0.05), increase exploration activity in open field test (P < 0.05), increase open arms duration (P < 0.05) and entries in elevated plus maze (P<0.001), and improve memory and learning in passive avoidance test (P < 0.05). The BDNF level was increased in IG mice and decreased in IG mice treated with GA. CONCLUSIONS Our results showed that GA improved depressive-/anxiety-like behaviors and cognitive dysfunction of SI reared mice without increasing the BDNF level which may be associated with other mechanisms of actions of GA.

Fundamental & Clinical Pharmacology, 2021

BACKGROUND Seizure occurs as a result of uncontrolled electrical disturbances within the brain. V... more BACKGROUND Seizure occurs as a result of uncontrolled electrical disturbances within the brain. Various biomolecules such as N-methyl-D-aspartate (NMDA), nitric oxide (NO) and cAMP response element-binding protein (CREB) have been implicated in the pathophysiology of seizure. Sumatriptan is a specific 5-Hydroxytryptamine 1B/1D receptor agonist and has neuroprotective effects in various neuropsychiatric disorders. OBJECTIVES In the current study, we tried to investigate the possible interaction of sumatriptan with NMDA/NO and CREB signaling pathway in PTZ induced seizure. METHODS For this purpose, various agonist and antagonist of NMDA such as MK-801 and Ketamine, NO precursor L-ARG, and NOS inhibitors L-NAME and 7-NI were co-administered with sumatriptan in PTZ induced seizure model. The level of nitrite in mice hippocampus was determined by Griess reaction. The gene expression of NR1, NR2A, NR2B and CREB were quantified by qRT-PCR. Furthermore, the involved neuronal nitric oxide synthase (nNOS) protein expression was examined via western blot analysis. RESULTS Effective dose of sumatriptan (1.2 mg/kg) alone and subeffective dose of sumatriptan (0.3 mg/kg) in combination with NMDA and/or NO antagonist, showed significant (P<0.001) anticonvulsant activity in mice. Furthermore, sumatriptan significantly inhibited the PTZ-induced mRNA expression of NR2A (P<0.0001), NR2B (P<0.05), and CREB (P<0.01). Also, the expression of nNOS protein in PTZ treated group was reversed by sumatriptan (P<0.01). CONCLUSION Hence, current findings suggest that the anticonvulsant effect of sumatriptan was due to down regulation of NMDA/NO and CREB signaling pathway.

… OF RESEARCH IN …, 2002

Introduction. Ni and Pb are metals with several suggested mechanisms for their toxicity on the bi... more Introduction. Ni and Pb are metals with several suggested mechanisms for their toxicity on the biological systems. We have recently investigated involvement of DNA in an electron transfer reaction as an enzyme. In this reaction non-fluorescent dichlorofluorescin (LDCF) is ...

Medical Journal of the Islamic Republic of Iran (MJIRI), May 15, 2001

The environmental pollutant 2, 3, 7, 8-tetra chlorodibenzo-p-dioxin (TCDD) has received much at t... more The environmental pollutant 2, 3, 7, 8-tetra chlorodibenzo-p-dioxin (TCDD) has received much at tention over the past few decades.! It is a highly toxic compound which is found as a contaminant in phenoxy acid, herbicides, chlorophenol, and also as a by-product during synthesis of industrial halogenated compounds. It has also been produced by various combustion pro-

Med. J. Islam. Repub. Iran, May 1, 2001

Janus green B (JG-B) dye is used for vital staining of mitochondria and its reduction and oxidati... more Janus green B (JG-B) dye is used for vital staining of mitochondria and its reduction and oxidation shows the electron transfer chain alteration. The defect in electron transfer chain of mitochondria by paraquat is linked to free radical formation. In this present study we compared the abilities of different angiotensin-converting enzyme inhibitors, captopril (a thiol ACEi), enalapril, and lisinopril (two nonthiol ACEi) on mitochondria toxicity due to paraquat. The rat liver mitochondria were first isolated by centrifuge (at 4 • C at a speed of 7,000 g) in a mixture of 0.25 M saccharose solution and 0.05 M Tris buffer. Various concentrations of paraquat (1, 5, 10 mM), enalapril (0.25, 0.5, 1 mM), lisinopril (0.01, 0.05, 0.1 mM), and captopril (0.08, 0.1, 1 mM) on the mitochondria isolated from the liver with respect to time were investigated. Paraquat at a concentration of 5 mM was determined to be significantly different compared to control values (P < 0.05) and captopril at a concentration of 0.08 mM, lisinopril (0.01 mM), and enalapril (0.25 mM) were found not to be significantly different from controls as found by spectroscopy at wavelength of 607 nm. Simultaneous treatment of mitochondria with captopril (0.08 mM) and paraquat (5 mM) significantly ameliorates the mitochondria toxicity of paraquat (5 mM) alone (P < 0.05). Our results show that captopril is a more effective antioxidant than the nonthiol ACEi. Lisinopril (0.01 mM) and enalapril (0.25 mM) did not significantly change the mitochondrial toxicity by paraquat (5 mM) (P > 0.05).

Journal of Cellular Physiology

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, Jan 19, 2017

In this study we investigated the protective effects and possible mechanisms of pirfenidone (PF) ... more In this study we investigated the protective effects and possible mechanisms of pirfenidone (PF) in paraquat (PQ)-induced lung injury and fibrosis in mice. Lung injury was induced by injection of PQ (20 mg/kg). Thereafter, mice orally received water and PF (100 and 200 mg/kg) for four weeks. After 28 days, the inflammation and fibrosis were determined in the lungs by analysis of histopathology, bronchoalveolar lavage fluid (BALF) cell count, lung wet/dry weight ratio, hydroxyproline content, and oxidative stress biomarkers. Expression of several genes involved in fibrogenesis and modulation of reactive oxygen species (ROS) production, such as TGF-β1, α-SMA, collagen Iα and IV, NOX1, NOX4, iNOS, and GPX1 were determined using RT-qPCR. PF significantly decreased the lung fibrosis and edema, inflammatory cells infiltration, TGF-β1 concentration, and amount of hydroxyproline in the lung tissue. PF dose-dependently improved the expression level of the studied genes to the near normal. De...

Journal of Molecular Liquids

Journal of Agricultural and Food Chemistry, 2005

An analytical method for the determination of OTC and TC residues in honey was developed. Sample ... more An analytical method for the determination of OTC and TC residues in honey was developed. Sample treatment involves an extraction in EDTA-McIlvaine buffer, followed by a solid-phase cleanup step. With regard to the cleanup procedure, different SPE cartridges were evaluated and the results presented. The method was validated according to the guidelines laid down by the 2002/657/EC European Decision parameters: decision limit (CcR) and detection capability (CC) were 20 and 21 µg/Kg and 49 and 50 µg/Kg for OTC and TC, respectively, and recoveries of OTC and TC from spiked samples, at three fortification levels, were higher than 87% for both compounds. The analytical method was applied to 57 honey samples.

Annals of the New York Academy of Sciences

ACS Chemical Neuroscience

Biomedicine & Pharmacotherapy