Protective Effects of Nebivolol Against Cisplatin-Induced Nephrotoxicity: An Experimental Study

Abstract

Background: Cisplatin is an effective and commonly used anticancer drug, but its therapeutic application is constrained by its potential to cause kidney injury. This experimental study investigated nebivolol protective effects, which is a third-generation selective β1-adrenoceptor blocker with additional β3-adrenoceptor agonistic activity, against cisplatin-induced nephrotoxicity (CIN) in rats. Methods: Twenty-one male Wistar rats were randomly allocated to three groups (n = 7 per group): control, cisplatin, and cisplatin plus nebivolol. Nebivolol (10 mg/kg/day, orally) was administered for 28 days, and cisplatin (6 mg/kg, intraperitoneally) was administered once on day 24. Renal function was assessed using serum and urine creatinine, blood urea nitrogen (BUN), serum urea, serum total protein, and creatinine clearance. Serum potassium and sodium concentrations were also measured. Renal oxidative stress was assessed using reduced glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA). Serum tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were measured as inflammatory markers. Hematoxylin and eosin (H&E) and periodic acid–Schiff (PAS) staining of kidney tissue sections were used to assess the histopathological changes. Results: Body and relative kidney weights showed no significant between-group differences. Cisplatin induced marked renal dysfunction, inflammation, oxidative stress, electrolyte disturbances, and histopathological injury. Compared with cisplatin alone, nebivolol significantly reduced serum creatinine, urea, BUN, IL-6, and TNF-α concentrations and renal MDA levels, while increasing urine creatinine, serum total protein, renal GSH, and SOD activity. Creatinine clearance was higher after nebivolol coadministration than after cisplatin alone, but the difference was not statistically significant (P = 0.077). Nebivolol also attenuated tubular necrosis and inflammatory-cell infiltration and improved tubular, glomerular, and brush-border morphology. However, its effects on electrolytes were incomplete: serum potassium increased without reaching statistical significance compared with the cisplatin group, whereas sodium decreased further. Conclusion: Nebivolol can ameliorate CIN in rats, as demonstrated by improvements in several renal functional, oxidative-stress, inflammatory, and histopathological outcomes. These findings support the nephroprotective potential of nebivolol but warrant confirmation in further preclinical studies.