Effect of alpha-mangostin in the prevention of behavioural and neurochemical defects in methylmercury-induced neurotoxicity in experimental rats. (2022)

• Record Type: Journal Article
• Authors: Sahu, Rakesh; Mehan, Sidharth; Kumar, Sumit; Prajapati, Aradhana; Alshammari, Abdulrahman; Alharbi, Metab; Assiri, Mohammed A.; Narula, Acharan S.
• Is Part Of: Toxicology reports. Volume 9(2022)
• Page Start: 977
• Page End: 998
• Publication Date: 2022
• Subjects: Methylmercury -- Amyotrophic lateral sclerosis -- ERK-1/2 -- Alpha-mangostin -- Oligodendrocytes -- Neuroprotection; Toxicology -- Periodicals; Clinical toxicology -- Periodicals; Drug-Related Side Effects and Adverse Reactions; Hazardous Substances; Poisoning; Toxicology; Electronic journals; Periodicals; Periodicals; 571.9505
• DOI: 10.1016/j.toxrep.2022.04.023
• Languages: English
• ISSNs: 2214-7500

Abstract

Abstract: Methylmercury (MeHg+) is a known neurotoxin that causes progressive motor neuron degeneration in the central nervous system. Axonal degeneration, oligodendrocyte degeneration, and myelin basic protein (MBP) deficits are among the neuropathological abnormalities caused by MeHg+ in amyotrophic lateral sclerosis (ALS). This results in demyelination and motor neuron death in both humans and animals. Previous experimental studies have confirmed that overexpression of the extracellular signalling regulated kinase (ERK1/2) signalling contributes to glutamate excitotoxicity, inflammatory response of microglial cells, and oligodendrocyte (OL) dysfunction that promotes myelin loss. Alpha-mangostin (AMG), an active ingredient obtained from the tree "Garcinia mangostana Linn, " has been used in experimental animals to treat a variety of brain disorders, including Parkinson's and Huntington's disease memory impairment, Alzheimer's disease, and schizophrenia, including Parkinson's disease and Huntington's disease memory impairment, Alzheimer's disease, and schizophrenia. AMG has traditionally been used as an antioxidant, anti-inflammatory, and neuroprotective agent.Accordingly, we investigated the therapeutic potential of AMG (100 and 200 mg/kg) in experimental rats with methylmercury (MeHg+)-induced neurotoxicity. The neuroprotective effect of AMG on behavioural, cellular, molecular, and other gross pathological changes, such as histopathological alterations in MeHg+ -treated rat brains, is presented. The neurological behaviour of experimental rats was evaluated using a Morris water maze (MWM), open field test (OFT), grip strength test (GST), and force swim test (FST). In addition, we investigate AMG's neuroprotective effect by restoring MBP levels in cerebral spinal fluid and whole rat brain homogenate. The apoptotic, pro-inflammatory, and oxidative stress markers were measured in rat blood plasma samples and brain homogenate. According to the findings of this study, AMG decreases ERK-1/2 levels and modulates neurochemical alterations in rat brains, minimising MeHg+ -induced neurotoxicity. Graphical Abstract: ga1 Highlights: Chronic methylmercury (MeHg+) exposure was used to cause motor neuron degeneration in rats. In MeHg-treated rats, oral administration of alpha-mangostin (AMG) improved behavioural, and neurochemical alterations. Effect of AMG related to anti-apoptotic, anti-inflammatory, and antioxidant properties via reducing ERK1/2 protein levels. AMG improved rat brain remyelination and enhancing MBP levels in rat brain homogenate, blood plasma, and CSF samples.