Document Type : Original Article
Authors
1
Department of Pharmacology, Faculty of Medicine, Minia University, Egypt
2
Department of Basic Health Sciences, Faculty of Medicine, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
3
Department 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.
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