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.