Cytoprotective Effects of Organosulfur Compounds against Methimazole-Induced Toxicity in Isolated Rat Hepatocytes
Journal Title: Advanced Pharmaceutical Bulletin - Year 2013, Vol 3, Issue 1
Abstract
Purpose: Methimazole is a drug widely used in hyperthyroidism. However, life-threatening hepatotoxicity has been associated with its clinical use. No protective agent has been found to be effective against methimazole-induced hepatotoxicity yet. Hence, the capacity of organosulfur compounds to protect rat hepatocytes against cytotoxic effects of methimazole and its proposed toxic metabolite, N-methylthiourea was evaluated. Methods: Hepatocytes were prepared by the method of collagenase enzyme perfusion via portal vein. Cells were treated with different concentrations of methimazole, N-methylthiourea, and organosulfur chemicals. Cell death, protein carbonylation, reactive oxygen species formation, lipid peroxidation, and mitochondrial depolarization were assessed as toxicity markers and the role of organosulfurs administration on them was investigated. Results: Methimazole caused a decrease in cellular glutathione content, mitochondrial membrane potential (ΔΨm) collapse, and protein carbonylation. In addition, an increase in reactive oxygen species (ROS) formation and lipid peroxidation was observed. Treating hepatocytes with N-methylthiourea caused a reduction in hepatocytes glutathione reservoirs and an elevation in carbonylated proteins, but no significant ROS formation, lipid peroxidation, or mitochondrial depolarization was observed. N-acetyl cysteine, allylmercaptan, and diallyldisulfide attenuated cell death and prevented ROS formation and lipid peroxidation caused by methimazole. Furthermore, organosulfur compounds diminished methimazole-induced mitochondrial damage and reduced the carbonylated proteins. In addition, these chemicals showed protective effects against cell death and protein carbonylation induced by methimazole metabolite. Conclusion: Organosulfur chemicals extend their protective effects against methimazole-induced toxicity by attenuating oxidative stress caused by this drug and preventing the adverse effects of methimazole and/or its metabolite (s) on subcellular components such as mitochondria.
Authors and Affiliations
Reza Heidari, Hossein Babaei, Mohammad Ali Eghbal
Keywords
Related Articles
- EP ID EP146252
- DOI 10.5681/apb.2013.023
- Views 106
- Downloads 0
Synthesis of Novel 1,4- Dihydropyridine Derivatives Bearing Biphenyl-2'-Tetrazole Substitution as Potential Dual Angiotensin II Receptors and Calcium Channel Blockers
Introduction: We report the synthesis of novel 1,4-dihydropyridine derivatives containing biphenyl-2'-tetrazole moieties. We hypothesized that merging the key structural elements present in an AT1 receptor antagonist wit...
Formulation, Characterization and Physicochemical Evaluation of Potassium Citrate Effervescent Tablets
Purpose: The aim of this study was to design and formulation of potassium citrate effervescent tablet for reduction of calcium oxalate and urate kidney stones in patients suffering from kidney stones. Methods: In this st...
Effect of Aflatoxin B1 on Growth of Bovine Mammary Epithelial Cells in 3D and Monolayer Culture System
Purpose: Many studies have been showed transfer of aflatoxins, toxins produced by Aspergillus flvaus and Aspergillus parasiticus fungi, into milk. These toxins are transferred into the milk through digestive system by ea...
Simultaneous Determination of Tetracyclines Residues in Bovine Milk Samples by Solid Phase Extraction and HPLC-FL Method
Introduction: Tetracyclines (TCs) are widely used in animal husbandry and their residues in milk may resultin harmful effects on human. The aim of this study was to investigate the presence of TCs residues in various bov...
The Effects of Lyophilization on the Physico-Chemical Stability of Sirolimus Liposomes
Purpose: The major limitation in the widespread use of liposome drug delivery system is its instability. Lyophilization is a promising approach to ensure the long-term stability of liposomes. The aim of this study was to...