| RESEARCH ARTICLE
|Year : 2021 | Volume
| Issue : 1 | Page : 25-30
Modulation of Liver P-Glycoprotien Expression May Contribute to Gossypin Protection against Methotrexate-Induced Hepatotoxicity
Mervat Mohamed1, Azza Kamal El Sheikh2, Hanaa Hassanien Mohammed3
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
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.
Dr. Mervat Mohamed
Department of Pharmacology, Faculty of Medicine, Minia University, Minya 61511
Source of Support: None, Conflict of Interest: None
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