Gossypin attenuates methotrexate-induced nephrotoxicity: Role of COX II/MMP-9 and fas ligand. | ||||
Minia Journal of Medical Research | ||||
Volume 31, Issue 1, January 2020, Page 182-196 PDF (1.12 MB) | ||||
Document Type: Original Article | ||||
DOI: 10.21608/mjmr.2022.221501 | ||||
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Authors | ||||
Heba M. Hafez1; Azza A.K. El-Sheikh2; Nagwa M. Zenhom3 | ||||
1Department of Pharmacology, Faculty of Medicine, Minia University, Egypt | ||||
2Department of Basic Health Sciences, Faculty of Medicine, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia. | ||||
3Department of Biochemistry, Faculty of Medicine, Minia University, Egypt. | ||||
Abstract | ||||
Methotrexate (MTX) is one of commonly used chemotherapeutic drugs, with well-known nephrotoxic effect. This study aimed to investigate the protective mechanisms of gossypin; a bioflavonoid present in plants, against MTX-induced nephrotoxicity. Rats were allocated into 4 groups: control, gossypin, MTX, and gossypin/MTX groups. Evaluation of renal function and histological images were done. Renal tissue oxidative markers of lipid peroxidation, total nitrite/nitrate (NO) level, reduced glutathione (GSH) and superoxide dismutase (SOD) were measured. Inflammatory and apoptotic markers as matrix metalloproteinase-9 (MMP-9) and beta-cell lymphoma-2 (Bcl-2) mRNA and protein expressions, respectively, as well as renal immunohistochemical expression of cyclooxygenase-II (COX-II) and fas ligand, were assessed. Renal P-glycoprotein (P-gp) expression was also measured. MTX caused a significant elevation in kidney functions, with noticeable elevation in oxidative stressmarkers’levels,aswell asCOX-II and fas ligand expressions. Moreover, MTX decreased renal antioxidant enzymes, P-gp level, and Bcl-2 expression. Gossypin administration significantly improved renal functions and oxidative insults, in addition to significant improvement of inflammatory and apoptotic parameters. Gossypin administration before MTX also ameliorated renal damage, at least in part, via modulation of P-gp level. In conclusion, gossypin may be an effective nephroprotective adjuvant to MTX through antioxidant, anti-apoptotic, and anti-inflammatory mechanisms. | ||||
Keywords | ||||
Gossypin; Methotrexate; Nephrotoxicity; P-glycoprotein; Matrix metalloproteinase-9 | ||||
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