The Role of Pomegranate Peel Extract in Improving Hepatotoxicity, and hMSH2 Expression in CCI 4 -Treated Rats

Recently, pomegranate fruit and its leaves have found wide usage as a natural treatment for several ailments. In this study, we investigated the restorative potentials of pomegranate (Punica granatum) peel extract against hepatic damage brought on by calcium tetrachloride (CCl 4 ) in rats and its effects on the human mutS homolog 2 (hMSH2) gene expression. Four groups of twenty male Wistar rats (n =5) were created at random. Group I was the untreated control group. Group II was given a dose of 0.4 ml CCl 4 intraperitoneally (IP) for two consecutive days/week for 3 weeks. Group III was given a daily dose (500 mg/ kg b.w) of pomegranate peel extract (PPE) for 3 weeks. Group IV received an IP of CCl 4 for two consecutive days/week for 3weeks followed by a daily oral dose of (500 mg/ kg b.w) of PPE for 3 weeks. Bodyweight, relative liver weight, serum AST, ALT, bilirubin, tissue GSH, and MDA, the expression of the hMSH2 gene, liver histology, and immunohistochemistry were assessed. Our results showed that the administration of CCl 4 to rats did not affect their body weight and relative liver weight. However, CCl 4 administration resulted in a decrease in tissue GSH, an increase in serum AST, ALT, bilirubin, lipid peroxidation, modification of liver histology, and immunohistochemistry, and the downregulation of the expression of the hMSH2 gene. Intriguingly, PPE treatment following CCl 4 administration to rats attenuated these changes. Taken together, our study reveals the potential of PPE for its use in the treatment of liver damage. administered group showed growing oval cells. c) Immunohistochemistry against CK7 for PPE only administered group, showing no visible oval cells. d) Immunohistochemistry against CK7 for CCl 4 + PPE group showed improved liver architecture to near normal with visible radiating hepatic cells. e) Immunohistochemistry against CK19 of the liver in the normal control group showed no visible oval cells. f) Immunohistochemistry against CK19 of the liver sections of the animals in the CCl 4 -administered group showed growing oval cells. g) Immunohistochemistry against CK19 for PPE only administered group, showing no visible oval cells. h) Immunohistochemistry against CK19 for CCl 4 + PPE group showed improved liver architecture to near normal with visible radiating hepatic cells. 4 administration to rats resulted in a decrease in serum liver damage biomarkers, restoration of liver histology and immunohistochemistry, an increase in the relative liver weight, and the upregulation of the hMSH2 gene expression. Taken together, our study reveals the potential of PPE for its use in the treatment of liver damage.