Piribedil and thymol mitigate vancomycin-evoked nephrotoxicity in rats through modulation of Keap-1/Nrf2/HO-1 and NF-κB/Bax/caspase 3 signalings.

Abstract

Nephrotoxicity is a sign in which endogenous or exogenous toxicants have damaged the kidney-specific detoxification and excretion processes. Vancomycin (VAN) exposure mostly causes kidney damage and a loss of body homeostasis regulation. This study aimed to investigate the protective effects of piribedil and thymol and its basic mechanisms against nephrotoxicity caused by VAN. Randomly, the animals were categorized into six groups (n = 8). For 7 d, Group I only received vehicles, Group II received piribedil (5 mg/kg/once daily, i.p.), Group III received thymol (25 mg/kg/once daily, i.p), Group IV was administered a single daily dose of VAN (200 mg/kg, i.p.), VAN+ piribedil was administered to Group V, and VAN + thymol was administered to Group VI. The findings showed that piribedil or thymol improved renal function parameters by an increase in serum albumin level in parallel to a decrease in serum creatinine and blood urea nitrogen (BUN) levels in addition to decreased levels of KIM-1 and serum cystatin C. Furthermore, enhanced oxidative stress biomarkers as GSH, myeloperoxidase (MPO), and malondialdehyde (MDA) as well as tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β), indicators of inflammatory mediators, were markedly reduced compared to VAN group. Moreover, piribedil or thymol markedly improved the histopathological aberrations provoked by VAN, increased the Nrf-2 and HO-1 renal protein expressions and reduced VAN-induced elevation of Keap-1 protein expression. In addition, NF-kB, Bax, and caspase 3 expression levels were considerably declined after piribedil or thymol co-treatment. These findings revealed that co-administration of piribedil or thymol with VAN may be a sensible therapeutic approach for reducing renal intoxication caused by VAN.