Document Type : Original paper
Department of Anatomy, School of Medicine, Arak University of Medical Sciences, Arak, Iran.
Traditional Medicine and Materia Medica Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Research Center and Molecular Medicine, Arak University of Medical Sciences, Arak, Iran.
Department of Biochemistry and Genetics, School of Medicine, Arak University of Medical Sciences, Arak, Iran.
Background and objectives: Trimethyltin chloride (TMT) is a chemical with neurotoxic effects on central nervous system. Carvacrol is a phenolic monoterpenoid with antioxidative properties derived from oregano, thyme, and other plants. We aimed to explore carvacrol effects on TMT-induced oxidative damage focusing on nuclear factor erythroid 2-related factor 2 (Nrf2)/ kelch-like ECH associated protein 1 (Keap1)/antioxidant response element (ARE) pathway and Sirt1. Methods: Thirty- two male rats were divided into four equal groups. Groups 1 and 2 received normal saline (control) and Dimethyl sulfoxide (DMSO, sham) for 21 days, respectively. Groups 3 and 4 were first treated with TMT (8 mg/kg) and then received normal saline and carvacrol (40 mg/kg) for 21 days, respectively. Finally, the levels of malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidant status (TOS) in serums and expressions of Nrf2, heme oxygenase-1 (Ho-1), Keap1, NADPH quinone oxidoreductase (NQO-1) and Sirtuin1 (Sirt1) in the hippocampus of the rats were quantified. Results: TMT significantly decreased Nrf2, HO1, NQO1, Sirt1 expressions and TAC level, while markedly increased expression of Keap-1 and levels MDA and TOS compared with control groups. Carvacrol treatment significantly upregulated Nrf2, HO1, NQO1, and Sirt1 along with an increase in TAC level as compared with TMT-treated rats. On the other hand, carvacrol caused a significant decrease in the expression of Keap-1 and levels of MDA and TOS compared with controls. Conclusion: Our results suggested the potential neuroprotective effects of carvacrol on TMT-triggered neurotoxicity probably by reciprocal regulation of Keap1/Nrf2/ARE pathway and Sirt1 activity.