Abstract
BACKGROUND: Oxidative stress (OS) and inflammation are the central pathogenic events in liver diseases. In this study, the protective and therapeutic role of Carica Papaya Linn. seeds extract (SE) was evaluated against the hepatotoxicity induced by carbon tetrachloride (CCl(4)) in rats. METHODS: The air-dried papaya seeds were powdered and extracted with distilled water. The phytochemical ingredients, minerals, and antioxidant potentials were studied. For determination of the biological role of SE against hepatotoxicity induced by CCl(4), five groups of adult male Sprague-Dawley rats were prepared (8 rats per each): C: control; SE: rats were administered with SE alone; CCl(4): rats were injected subcutaneously with CCl(4); SE-CCl(4) group: rats were administered with SE orally for 2 weeks before and 8 weeks during CCl(4) injection; SE-CCl(4)-SE group: Rats were administered with SE and CCl(4) as mentioned in SE-CCl(4) group with a prolonged administration with SE for 4 weeks after the stopping of CCl(4) injection. Then, the markers of OS [lipid peroxidation (LP) and antioxidant parameters; glutathione (GSH), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione peroxidase (GPx)], inflammation [nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α, interleukin (IL)-6], fibrosis [transforming growth factor (TGF)-β], apoptosis [tumor suppressor gene (p53)], liver and kidney functions beside liver histopathology were determined. RESULTS: The phytochemical analyses revealed that SE contains different concentrations of phenolics, flavonoids, terpenoids, and minerals so it has potent antioxidant activities. Therefore, the treatment with SE pre, during, and/or after CCl(4) administration attenuated the OS induced by CCl(4) where the LP was reduced, but the antioxidants (GSH, SOD, GST, and GPx) were increased. Additionally, these treatments reduced the inflammation, fibrosis, and apoptosis induced by CCl(4), since the levels of NF-κB, TNF-α, IL-6, TGF-β, and p53 were declined. Accordingly, liver and kidney functions were improved. These results were confirmed by the histopathological results. CONCLUSIONS: SE has protective and treatment roles against hepatotoxicity caused by CCl(4) administration through the reduction of OS, inflammation, fibrosis, and apoptosis induced by CCl(4) and its metabolites in the liver tissues. Administration of SE for healthy rats for 12 weeks had no adverse effects. Thus, SE can be utilized in pharmacological tools as anti-hepatotoxicity.