hepatoprotective effect by inducing the antioxidant defense mechanism.
Aim of the Study: To evaluate aging-related impacts on the hepatic structure and function and the possible mitigating role of MO extract, with clarifying the mechanistic role of autophagy in aged rat models.
Material and Methods: Twenty four rats, aged 3 months, were assigned into 4 groups as following, group I: adult control, group II: administered MO leaf aqueous extract (50 mg/kg body weight) by nasogastric tube for 4 months, group III: received no treatment till age 20 months, and group IV: received no treatment till age 16 months, and then received MO leaf aqueous extract for 4 months. At the time of sacrificing, serum liver enzymes (aspartate aminotransferase and alanine aminotransferase) were measured and the hepatic specimens were processed for light and electron-microscopic assessment and analysis of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), and mammalian target of rapamycin (mTOR) gene expression.
Results: The aged rats revealed significant elevation of liver enzymes and hepatic malondialdehyde as well as reduction of hepatic glutathione content. Aging also inhibited autophagy via upregulation of autophagy inhibitory genes; PI3K, Akt, and mTOR. Immuno-histopathological evaluation of the hepatic tissue of aged rats displayed deteriorated cytoarchitecture in terms of hydropic degeneration, congested veins, and inflammatory infiltrates in addition to increased glial fibrillary acidic protein expression and decreased microtubule-associated protein 1A/1B-light chain 3 (LC3) expression. MO administration to the aged rats promoted significant amelioration of aging-induced hepatic dysfunction and tissue alterations, counteracted oxidative stress and enhanced autophagy via downregulation of PI3K, Akt and mTOR genes
Conclusion: MO can reduce aging-induced structural and functional liver damage by combating oxidative stress, and stimulation of autophagy through downregulation of the PI3K/Akt/mTOR signaling pathway.