Modulation of liver p‑glycoprotien expression may contribute to gossypin protection against methotrexate‑induced hepatotoxicity
- Vol.53(1), Jan-Feb
- Mumbai Wolter Kluwer 2021
- 25-30p.
OBJECTIVES: Methotrexate (MTX) is a broadly used anticancer. Its major side effect is hepatotoxicity. Gossypin is a flavonoid has a hepatoprotective effect as well as antitumor property. The study aimed at inspecting the protective effect of gossypin against MTX hepatotoxicity. MATERIALS AND METHODS: Twenty‑four adult male rats arranged into four groups (six rats each): control, gossypin control, MTX, and MTX+ gossypin. Animals were orally administered gossypin at 10 mg kg‑1 day‑1 for 7 days. MTX was injected i.p. (20 mg/kg‑1 once) on 5th day. Liver enzyme and oxidative stress markers were assessed. BAX, transforming growth factor‑beta (TGF‑β) gene expressions, and P‑glycoprotein (P‑gp) were assessed. The histopathological study as well as the immunohistochemical study for hepatic caspase 3 and nuclear factor kappa‑B (NFκ‑B) was done. RESULTS: MTX produced a significant increase of liver enzymes and distortion of hepatic architecture alongside with increased the hepatic collagen content. MTX administration significantly increased the oxidative stress markers and upregulated the pro‑apoptotic BAX and the pro‑fibrogenic TGF‑β. MTX increased caspase 3 and NFκ‑B expression, while diminished the expression of P‑gp. Gossypin pretreatment improved the previous parameters, restored the normal hepatic architecture, reduced the hepatic fibrosis, and regained nearly normal expressions for BAX, TGF‑β, caspase 3, and NFκ‑B. Gossypin caused more reduction in P‑gp hepatic expression. CONCLUSIONS: Gossypin may be a valuable adjuvant therapy that protects the liver against MTX toxicity through antioxidant, anti‑inflammatory, antiapoptotic mechanisms, and mediated P‑gp expression reduction.