Effect of Methanol Extract of Mangifera indica on Mitochondrial Membrane Permeability Transition Pore in Normal Rat Liver and Monosodium Glutamate-induced Liver and Uterine Damage

Abstract

Introduction: The mitochondrion has been known to play a crucial role in the induction of apoptosis as a result of the opening of the mitochondrial permeability transition (mPT) pore which results to the release of cytochrome C and consequently, lead to cell death (apoptosis). Aim: The aim of this study was to investigate the influence of crude methanol extract of Mangifera indica (MEMI) on mitochondrial-mediated apoptosis via induction of MMPT pore opening in vitro and in vivo. Methods: Mitochondria, isolated from female albino rat liver (between 90-100 g), were exposed to varying concentrations (10, 30, 50, 70, and 90 μg/ml) of MEMI. Opening of the pore, cytochrome c release, mitochondrial ATPase activity and extent of mitochondrial lipid peroxidation were assessed spectrophotometrically. Histological examinations were also carried out on the liver and uteruses of normal and monosodium glutamate (MSG)-treated rats. Results: The in vitro results showed a significant concentration-dependent induction of pore opening by 1.5, 10.3, 11.5, 13.1 and 17.4 folds, respectively. Oral administration of MEMI at varying doses of 100, 200 and 400 mg/kgbw also showed an induction  folds of 0.4, 1.9 and 2.3, respectively, after 14 days, and more significantly, induction folds of 3.4, 6.3 and 15.4, respectively, after 28 days of treatment. Also, MEMI caused a significant release of cytochrome C and enhancement of ATPase activity both in vitro and in vivo in a concentration and dose-dependent manner. The histological findings also showed that MEMI ameliorated the damage induced in the liver and uterus of MSG-treated rats. It also reduced the MSG-induced uterine hyperplasia in the co-administered group. Conclusion: These results suggest that MEMI contains bioactive agents that can induce mitochondrial-mediated apoptosis and ameliorate MSG-induced liver damage and uterine hyperplasia. This might be relevant in disease conditions where apoptosis needs to be upregulated.