Background This study aimed to evaluate the protective effects of alamandine, a new member of the angiotensin family, against doxorubicin (DOX)-induced nephrotoxicity in rats. Methods Rats were intraperitoneally injected with DOX (3.750 mg/kg/week) to reach a total cumulative dose of 15 mg/kg by day 35. Alamandine (50 µg/kg/day) was administered to the rats via mini-osmotic pumps for 42 days. At the end of the experiment, rats were placed in the metabolic cages for 24 h so that their water intake and urine output could be measured. After scarification, the rats’ serum and kidney tissues were collected, and biochemical, histopathological, and immunohistochemical studies were carried out. Results DOX administration yielded increases in pro-inflammatory cytokines, including interleukin (IL)-1β and IL-6, pro-fibrotic proteins transforming growth factor-β (TGF-β), pro-inflammatory transcription factor nuclear kappa B (NF-κB), kidney malondialdehyde (MDA), creatinine clearance, blood urea nitrogen (BUN), and water intake. On the other hand, the DOX-treated group exhibited decreased renal superoxide dismutase (SOD), renal glutathione peroxidase (GPx) activity, and urinary output. Alamandine co-therapy decreased these effects, as confirmed by histopathology and immunohistochemical analysis. Conclusions The results suggest that alamandine can prevent nephrotoxicity induced by DOX in rats.
Background: The objective of this study was to evaluate the protective effects of alamandine, a new member of the angiotensin family, against doxorubicin (DOX)-induced nephrotoxicity in rats.Methods: Rats, intraperitoneally injected with DOX (3.750 mg/kg/week) to reach total cumulative dose of 15 mg/kg on day 35. Alamandine (50µg/kg/day) was administered to the rats via mini-osmotic pumps for 42 days. At the end of experiment, rats were placed in the metabolic cages for 24 h for measurement of water intake and urine output. After scarification, Serum and kidney tissues were collected, and biochemical, histopathological and immunohistochemical studies were carried out.Results: Inflammatory cytokines (IL-1β, IL-6), pro-fibrotic mediator (TGF-β), pro-inflammatory transcription factor (NF-kB), renal MDA, creatinine clearance, BUN, and water intake were increased by DOX administration. On the other hand, renal SOD, renal GPx activity and urinary output were decreased in the DOX-treated group. Alamandine co-therapy decreased these effects, as confirmed by histopathology and immunohistochemical analysisConclusion: The results of this study suggest that alamandine has the potential in preventing the nephrotoxicity induced by DXR in rats.
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