Nebivolol Ameliorates Cisplatin‐Induced Nephrotoxicity in Rats

Abstract

Treatment with cisplatin is associated with dose-limiting side effects, mainly nephrotoxicity. On the other hand, nebivolol, a b 1 -adrenoceptor antagonist, exhibits vasodilatory and antioxidative properties. This study aimed to determine whether nebivolol possesses a protective effect against cisplatin nephrotoxicity and explore many mechanisms underlying this potential effect. Nephrotoxicity was induced in Wistar rats by a single intraperitoneal injection of cisplatin (6 mg/kg) on day 2. Nebivolol (10 mg/kg) was administered orally for 7 consecutive days. Nebivolol showed a nephroprotective effect as demonstrated by the significant reduction in the elevated levels of serum creatinine and urea as well as renal levels of malondialdehyde, nitric oxide products (nitrite/nitrate), inducible nitric oxide synthase, tumour necrosis factor-alpha, caspase-3, angiotensin II and endothelin-1 with a concurrent increase in renal levels of reduced glutathione and endothelial nitric oxide synthase compared to untreated rats. Histopathological examination confirmed the nephroprotective effect of nebivolol. Pre-treatment with N x -nitro-L-arginine methyl ester, the non-specific nitric oxide synthase inhibitor, partially altered the protection afforded by nebivolol. In conclusion, nebivolol protects rats against cisplatin-induced nephrotoxicity that is most likely through its antioxidant, anti-inflammatory and antiapoptotic effects as well as by abrogation of the augmented angiotensin II and endothelin-1 levels.

Protective Effects of Vasodilatory Î’eta-Blockers Carvedilol and Nebivolol against Glycerol Model of Rhabdomyolysis-Induced Acute Renal Failure in Rats

“…Co-treatment of rats with either Carv or Nebi showed a significant protective effect against the current Gly-induced RM-ARF model. This observed renoprotective effect is in agreement with the findings of studies that used Carv or Nebi as a protective agent against other models of ARF in which restoration of the normal levels of renal function biomarkers was reported [ 49 , 50 ].…”

“…The significant attenuation of Gly-induced oxidative stress in the rats treated with Carv or Nebi indicates that antioxidant pathway played a role in the renoprotective effects of both drugs. Many studies also reported this antioxidant effect of Carv and Nebi [ 49 , 51 ]. Carv has been found to scavenge oxygen radicals and inhibit their release from activated neutrophils [ 52 , 53 ].…”

Different effects of selective β1-adrenoceptor antagonists, nebivolol or atenolol in acetaminophen-induced hepatotoxicity of rats

“…In contrary, nebivolol markedly increased expression of eNOS which was weakly expressed with APAP hepatotoxicity. It was reported that nebivolol enhanced eNOS expression [25][26][27] and reduced iNOS expression [28]. Induction of iNOS expression was associated with hepatotoxicity of other models, and its reduction was linked to hepatoprotective effect [29][30][31].…”

Impact of Diabetes Complications on Breast Cancer Screening, Diagnosis, and Prognosis among Elderly Women with Pre-existing Diabetes Using the SEER-Medicare Dataset

“…The most frequent diabetes-related complications are cardiovascular diseases and atherosclerosis, and the main troublesome complications in the elderly are heart and kidney insufficiencies (Chentli et al, 2015). These complications could exacerbate chemotherapy-induced toxicity and worsen cancer symptoms (Psarakis, 2006;Malik et al, 2016;Morsy & Heeba, 2016;).…”

“…Although the severity of diabetes complications could contribute to higher mortality among women with diabetes, little is known about the impact of severity of diabetes-related complications on risk of all-cause mortality among incident BC cases. Evidence from previous literature has revealed that the presence of some diabetes complications could affect cancer therapy (Morsy & Heeba, 2016;Peairs et al, 2011;, which could impact patients' health outcomes. However, there are limited evidence in the literature on the direct impact of overall severity of diabetes-related complications on all-cause mortality of incident BC after controlling for cancer therapy and other possible risk factors.…”