Methylmercury exposure develops atherosclerotic risk factors in the aorta and programmed cell death in the cerebellum: ameliorative action of Celastrus paniculatus ethanolic extract in male Wistar rats

Abstract

Methylmercury (MeHg) is a bioaccumulative global environmental contaminant present in fishes and seafood. MeHg is the methylated form of mercury emitted from diverse anthropogenic and natural sources. MeHg is accumulated in the aquatic environment and eventually reaches human system via food chain by biomagnification. We have reported previously that the neurotoxic effect of MeHg in rat cerebellum is mitigated by the administration of an ayurvedic medicinal plant, Celastrus paniculatus ethanolic extract. The present study has focussed to further explore the mechanism of action of Celastrus paniculatus against MeHg-induced neurotoxicity in the cerebellum. We have also inspected the effect of Celastrus paniculatus (CP) against MeHg-induced atherosclerotic risk factors like alterations in antioxidant levels, aortic lipid profile, and aortic histology by MeHg in the largest vasculature, aorta, which are the initiating factors of cardiovascular diseases. Male Wistar rats were divided as (i) control, (ii) MeHg (5 mg/kg b.w.), (iii) MeHg + CP (200 mg/kg b.w.), and (iv) CP alone (200 mg/kg b.w.). All were given orally for 21 days. In cerebellum Celastrus paniculatus, there were increased mitochondrial electron transport chain (p < 0.05) activity, reduced cytochrome c release (p < 0.05), and caspase 3 mRNA expression (p < 0.05). In the aorta, MeHg-induced oxidative stress, lipid profile changes, and endothelial denudation were ameliorated by Celastrus paniculatus. Hence, we conclude that Celastrus paniculatus protects against MeHg toxicity by inhibiting mitochondrial cytochrome c/caspase 3 apoptotic pathway in the cerebellum and reducing the development of atherosclerotic risk factors in the aorta.