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 RESEARCH ARTICLE
Year : 2021  |  Volume : 53  |  Issue : 1  |  Page : 25-30

Modulation of Liver P-Glycoprotien Expression May Contribute to Gossypin Protection against Methotrexate-Induced Hepatotoxicity


1 Department of Pharmacology, Faculty of Medicine, Minia University, Minya, Egypt
2 Department of Pharmacology, Faculty of Medicine, Minia University, Minya, Egypt; Department of Basic Health Sciences, Faculty of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
3 Department of Histology, Faculty of Medicine, Minia University, Minya, Egypt

Correspondence Address:
Dr. Mervat Mohamed
Department of Pharmacology, Faculty of Medicine, Minia University, Minya 61511
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijp.IJP_824_19

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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.






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