Vancomycin-induced acute kidney injury in rats: beneficial effects deriving from the co-administration of tadalafil or vitamin C

Abstract

Background: Vancomycin (VAN) is widely employed in clinical settings for the treatment of severe infections attributable to multi-resistant bacteria, with a notable emphasis on Gram-positive strains. However, its therapeutic usage is significantly hampered by the potential for acute kidney injury (AKI); specifically, the nephrotoxic effects it can exert. In controlled experimental studies, the intraperitoneal (i.p.) administration of VAN at a dose of 400 mg/kg/day over a consecutive seven-day period has been shown to induce considerable AKI in rats. In addressing this concern, vitamin C (VC), recognized traditionally for its antioxidant properties, has been utilized to mitigate various forms of organ damage and inflammatory responses, primarily by diminishing oxidative stress and attenuating inflammation. Concurrently, tadalafil (TAD), a phosphodiesterase type-5 inhibitor commonly associated with the treatment of erectile dysfunction, is also noted for its beneficial anti-inflammatory and antioxidant effects, alongside vasodilatory properties. Aim: This study was designed in order to investigate the protective capabilities of TAD or VC against the VAN-induced nephrotoxic effects in a rat model of AKI. Methodology: A total of 24 male albino Wistar rats were allocated into four distinct groups for the purpose of comparative analysis. Following treatment, both kidney and blood samples were obtained for further evaluation. The study randomized the rats into four categories: group 1 served as the control group, group 2 received VAN at a dosage of 400 mg/kg (via an i.p. injection on a daily basis), group 3 was administered VAN (400 mg/kg; i.p., daily) in conjunction with TAD at a dose of 5 mg/kg daily, and group 4 was given VAN (400 mg/kg; i.p., daily) alongside VC at a dosage of 200 mg/kg daily. Results: Evaluations included the measurement of renal function indicators such as the serum levels of urea, of creatinine, and the creatinine clearance. Additionally, the analysis involved the assessment of antioxidant markers in renal tissue homogenates, including malondialdehyde (MDA), glutathione, and superoxide dismutase. To further elucidate the inflammatory response, indices such as the levels of the tumor necrosis factor-alpha, the interleukins (IL)-1β and IL-6, and the nuclear factor-κB were evaluated within the renal tissue homogenate samples of the studied rats. The administration of VAN resulted in a marked elevation of renal biomarkers and inflammatory indices, alongside a significant reduction in antioxidant levels, with an exception for MDA (which exhibited increased levels); these changes reached statistical significance (p<0.05) when measured against the control group. In contrast, the supplementation with TAD or VC was effective in significantly lowering the serum levels of both renal and inflammatory indicators when compared to the group treated solely with VAN. Furthermore, antioxidant measurements improved, alongside a reduction in MDA levels, thereby demonstrating significant differences (p<0.05). Conclusion: The findings of this study reveal that both TAD and VC provide a degree of renal protection against the VAN-induced damage by enhancing kidney function markers and, concurrently, lessening oxidative stress and inflammatory responses associated with nephrotoxicity.