Protective effect of alamandine on doxorubicin‑induced nephrotoxicity in rats

Abstract

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.

Cardiorenal Protective Effect of Costunolide against Doxorubicin-Induced Toxicity in Rats by Modulating Oxidative Stress, Inflammation and Apoptosis

“…Exposure to DXB significantly increased cardiorenal expression of p53, an important apoptotic mediator. Earlier studies demonstrated that DXB toxicity induces up-regulation in p53 protein in the kidney, testes and cardiac tissues [ 37 , 38 , 39 , 40 ]. However, COST treatment down-regulated cardiorenal apoptosis by inhibiting increases in p53 intensity, thus showing protective effects against DXB-mediated toxicity.…”

α-Bisabolol Attenuates NF-κB/MAPK Signaling Activation and ER-Stress-Mediated Apoptosis by Invoking Nrf2-Mediated Antioxidant Defense Systems against Doxorubicin-Induced Testicular Toxicity in Rats

“…The transcriptional activator NF-κB regulates various inflammatory factors and plays a significant role in the pathophysiology of the DOX-induced inflammatory cascade in organ injuries [ 46 , 47 , 48 ]. NF-κB activation influenced by ROS overproduction is mainly responsible for the changes in the inflammatory cascades via the mediation of pro-inflammatory cytokines and mediators (TNF-α, IL-1β, IL-6, COX-2, and iNOS) [ 49 ]. NF-κB activation is inevitable during the prevailing dominance of pro-inflammatory mediators, and this positive feedback mechanism is predicted to augment pro-inflammatory signals which aggravate tissue injuries [ 50 ].…”

Alamandine: Potential Protective Effects in SARS-CoV-2 Patients

“…Alamandine (50 μ g/kg/day, S.C. for 42 days) also alleviated the negative proinflammatory effects of doxorubicin (DOX) (e.g., increased TNF- α , IL-1 β , IL-6, TGF- β , and NF- κ B levels) [ 59 , 60 ]. Moreover, a study in rats indicated that alamandine can drastically control DOX-induced cardiotoxicity and nephrotoxicity by altering rats' antioxidant status, apoptosis, and inflammatory cytokines [ 59 ].…”

“…Alamandine (50 μ g/kg/day, S.C. for 42 days) also alleviated the negative proinflammatory effects of doxorubicin (DOX) (e.g., increased TNF- α , IL-1 β , IL-6, TGF- β , and NF- κ B levels) [ 59 , 60 ]. Moreover, a study in rats indicated that alamandine can drastically control DOX-induced cardiotoxicity and nephrotoxicity by altering rats' antioxidant status, apoptosis, and inflammatory cytokines [ 59 ]. Furthermore, Liu et al recently showed that alamandine (2 μ g/kg/day, S.C. for 21 days) can inhibit bleomycin-induced lung fibrosis by reducing oxidative stress and activating autophagy through the MrgD receptor [ 61 ].…”