Effect of silymarin on the relative gene expressions of some inflammatory cytokines in the liver of CCl4-intoxicated male rats.

The intensive exposure of the liver cells to any type of noxae, such as viruses, drugs, alcohols, and xenobiotics could induce hepatic inflammation through the upregulation of gene expression of several fibrotic and inflammatory mediators. So, our study assessed the role of silymarin on the inflammatory response induced by carbon tetrachloride (CCl4) as an example of xenobiotics on liver tissues in male rats. Forty-eight Wister male rats (weight: 130 ± 10) were housed for 14 days and then divided randomly into six groups: control, SLY: rats received only silymarin orally for 12 weeks (daily), CO: rats were injected with corn oil for 8 weeks (3 times weekly), CCl4: rats were injected with CCl4 solubilized in corn oil for 8 weeks (day by day), Treated: rats received silymarin for 4 weeks after CCl4 injection, Protected: rats received silymarin for 4 weeks before and 8 weeks during CCl4 injection. When the treatment period for the rats was over, they underwent scarification after anesthesia. Then, the sera were extracted from the collected blood for the determination of irisin levels, liver functions, and lipid profiles. Liver tissues were separated for the histopathological examinations, the determination of oxidative stress (OS) parameters content, and the relative gene expression of inflammatory cytokines; nuclear factor kappa (NF)-κB, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, cyclooxygenase (COX)-2, and transforming growth factor beta (TGF-ß). The findings showed that silymarin reduced liver inflammation by overcoming the OS process and inflammatory cytokines production which was stimulated by CCl4. These results were confirmed by histopathology of liver tissues.

Prophylactic and curative effects of Carica papaya Linn. pulp extract against carbon tetrachloride-induced hepatotoxicity in male rats.

Several chemicals and medications induce cellular damage in various organs of the body by activating reactive substances' metabolism leading to various pathological conditions including liver disease. In this study, we evaluated the prophylactic and curative effects of Carica papaya Linn. pulp water extract (PE) against CCl4-induced rat hepatotoxicity. Five groups of rats were created, control, PE, CCl4, (PE-CCl4): The rats were administered with PE pre and during CCl4 injection, and (PE-CCl4-PE): The rats were administered with PE pre, during, and after CCl4. The markers of oxidative stress ("OS": oxidant and antioxidants), inflammation [nuclear factor-κB, tumor necrosis factor-α, and interleukin-6], fibrosis [transforming growth factor-ß], and apoptosis [tumor suppressor gene (p53)] were evaluated. Additionally, liver functions, liver histology, and kidney functions were measured. Also, PE characterization was studied. The results showed that PE, in vitro, has a high antioxidant capacity because of the existence of phenolics, flavonoids, tannins, terpenoids, and minerals. Otherwise, the PE administration [groups (PE-CCl4) and (PE-CCl4-PE)] exhibited its prophylactic and therapeutic role versus the hepatotoxicity induced by CCl4 where PE treatment improved liver functions, liver histopathology, and renal functions by decreasing oxidative stress, inflammation, fibrosis, and apoptosis induced by CCl4. Our study elucidated that PE contains high amounts of phenolics, flavonoids, tannins, terpenoids, and ascorbic acid. So, PE exerted significant prophylactic and curative effects against hepatotoxicity induced by CCl4. These were done by enhancing the markers of antioxidants and drug-metabolizing enzymes with reductions in lipid peroxidation, inflammation, fibrosis, and apoptosis. PE administration for healthful rats for 12 weeks had no negative impacts. Consequently, PE is a promising agent for the prohibition and therapy of the toxicity caused by xenobiotics.

The antioxidant and anti-inflammatory effects of Carica Papaya Linn. seeds extract on CCl4-induced liver injury in male rats.

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 (CCl4) 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 CCl4, five groups of adult male Sprague-Dawley rats were prepared (8 rats per each): C: control; SE: rats were administered with SE alone; CCl4: rats were injected subcutaneously with CCl4; SE-CCl4 group: rats were administered with SE orally for 2 weeks before and 8 weeks during CCl4 injection; SE-CCl4-SE group: Rats were administered with SE and CCl4 as mentioned in SE-CCl4 group with a prolonged administration with SE for 4 weeks after the stopping of CCl4 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)-ß], 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 CCl4 administration attenuated the OS induced by CCl4 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 CCl4, since the levels of NF-κB, TNF-α, IL-6, TGF-ß, 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 CCl4 administration through the reduction of OS, inflammation, fibrosis, and apoptosis induced by CCl4 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.