Reno-protective effects of benzbromarone and tart cherry against cyclosporine A-induced nephrotoxicity via SIRT1/PPAR-γ/ABCG2 | ||
| Journal of Advanced Medical and Pharmaceutical Research | ||
| Articles in Press, Accepted Manuscript, Available Online from 07 July 2025 PDF (1.11 M) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/jampr.2025.378476.1096 | ||
| Authors | ||
| Nageh Ahmed El-Mahdy1; Yasmin Tarek Saad* 1, 2; Laila Ahmed Ramadan2; Sally El-Sayed Abu Risha1 | ||
| 1Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt | ||
| 2Department of Pharmacology & Toxicology, Faculty of Pharmacy, Egyptian Russian University, Cairo, Egypt | ||
| Abstract | ||
| Cyclosporine A (CsA), a widely used immunosuppressant in organ transplantation, is associated with nephrotoxicity. This research study investigated the potential protective effects of benzbromarone, a uricosuric agent, and tart cherry, a natural antioxidant, against CsA-induced nephrotoxicity in a rat model. Fifty male albino rats were split at random into five groups: control group, CsA group, CsA + benzbromarone group, CsA + tart cherry group, and combination group. Biochemical markers of kidney function, oxidative stress, and inflammation were evaluated after four weeks of treatment. Histopathological analysis of kidney tissue and molecular assessments of SIRT1, PPARγ, URAT1, and ABCG2 expressions were also assessed. Results demonstrated that CsA treatment significantly elevated serum creatinine, and uric acid levels, along with increased oxidative stress markers (MDA) and inflammatory markers (TNF-α, IL-6, NF-κB). Benzbromarone and tart cherry, individually and in combination, significantly reduced these levels. The combination therapy demonstrated superior efficacy, with significant improvements in renal function and greater reductions in oxidative stress and inflammation compared to each drug alone. Histopathological analysis confirmed the protective effects, showing reduced kidney damage in the combination group. Molecular analysis revealed upregulation of SIRT1, PPARγ, and ABCG2, and downregulation of URAT1 in treated groups, with the combination therapy exhibiting the most significant effects. In conclusion, both benzbromarone and tart cherry, especially in combination, protect against CsA-induced nephrotoxicity through antioxidant, anti-inflammatory, and uricosuric activities. These results show that combination therapy might be a promising therapeutic approach for mitigating CsA-associated kidney damage, warranting further clinical investigation. | ||
| Keywords | ||
| Benzbromarone; Tart cherry; Cyclosporine A; Hyperuricemia; Oxidative stress; Nephrotoxicity | ||
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