Protective effect of alamandine on doxorubicin‑induced nephrotoxicity in rats

BMC Pharmacology and Toxicology

Ava Soltani Hekmat¹  Ameneh Chenari¹  Hiva Alipanah¹  Kazem Javanmardi¹ 

[1] Department of Physiology, Fasa University of Medical Sciences, Ebn-E-Sina SQ, Fasa, Iran;

关键词: Alamandine;    Doxorubicin;    Kidney;    Cytokine;    Oxidative Stress;    Apoptosis;    Immunohistochemistry;   

DOI  :  10.1186/s40360-021-00494-x

来源: Springer

【 摘 要 】

BackgroundThis study aimed to evaluate the protective effects of alamandine, a new member of the angiotensin family, against doxorubicin (DOX)-induced nephrotoxicity in rats.MethodsRats 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.ResultsDOX 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.ConclusionsThe results suggest that alamandine can prevent nephrotoxicity induced by DOX‎ in rats.

【 授权许可】

CC BY