Carvacrol Ameliorating Effects on Trimethyltin Chloride-Induced Neurotoxicity by Modulating the Interplay between Nrf2/Keap1/ARE Pathway and Sirt1

Abstract

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.

Keywords

• carvacrol
• keap1
• nrf2
• sirt1
• trimethyltin chloride