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Abstract

Plant parts play a crucial function to protect organisms from the toxic/carcinogenic effects of some compounds. The present study was carried out to investigate the protective effects of Graviola aqueous extract (GAE) against carbon tetrachloride (CCl 4 ) which induced hepatic injury in rats. Thirty male albino Wistar rats were divided into five groups: group I was used as controls, group II received daily GAE (300 mg/kg bw) alone orally for six weeks, group III received by IP injection CCl 4 in olive oil (50% V/V, 2 ml/kg bw), twice a week for two weeks, group IV, CCl 4 +GAE (curative group) injected CCl 4 twice a week for two weeks then concomitant with GAE (300 mg/kg BW) daily for next four weeks, and group V, GAE+CCl 4 (prophylactic group), received GAE, 300 mg/kg/day once daily orally four weeks, then concomitant with CCl 4 twice a week for next two weeks. The obtained results showed that the administration of CCl 4 caused hepatotoxicity as monitored by the significant (p≤0.05) increase in the levels of hepatic markers enzymes (alanine aminotransferase, ALT, aspartate aminotransferase, AST and alkaline phosphatase, ALP), total bilirubin (TB) and a decrease in hematological parameters such as white blood cell (WBC), red blood cell count (RBC), and blood platelet count (PLT). Also, our results showed that CCl 4 caused a significant (p≤0.05) increase in oxidative stress markers (malondialdehyde, MDA, reactive oxygen species, ROS, nitric oxide, NO), pro-inflammatory tumor necrosis factor-alpha (TNF-α,) level, and proapoptotic markers caspase-3, and B-cell lymphoma 2 (BCL-2)-like protein 4 (Bax). Furthermore, a significant (p≤0.05) decrease in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), reduced glutathione (GSH), and an antiapoptotic agent B-cell lymphoma 2 (Bcl-2) was observed in liver tissue. The detected CCl 4 effects were normalized by GAE administration, either a prophylactic or curative dose. Besides, GAE reduced the histopathological changes induced by CCl 4 .In conclusion, GAE was effective in both protecting and enhancing the liver deficits induced by CCl 4 through many potential mechanisms including antioxidant, antiinflammatory, antiapoptotic properties. Therefore, Graviola extracts up to 300 (mg/kg bw) could be considered a promising hepatoprotective supplement but more human clinical trials are also needed to validate the findings of the current research.