Effect of dexpanthenol on glycerol-induced acute kidney injury by targeting the PGC-1α/SIRT3 pathway

Abstract

Rhabdomyolysis (RM) can lead to life-threatening myoglobinuric acute kidney injury (AKI). Despite various treatment modalities for AKI, their effectiveness remains limited. Dexpanthenol (DEX) is an antioxidant, anti-inflammatory, and anti-apoptotic agent with demonstrated protective effects on various tissues. The current study aimed to investigate the protective effects and genetic mechanisms of DEX in AKI due to glycerol-induced RM. Thirty-two female Wistar Albino rats weighing between 250-300 g were allocated into four groups of eight rats each. The control group was given five days of intraperitoneal saline. The RM group was treated with an intramuscular injection of 8 ml/kg of 50% glycerol solution. The RM + DEX group was administered an intramuscular injection of 8 ml/kg of 50% glycerol solution and an intraperitoneal injection of 500 mg/kg DEX for five days, starting one hour after glycerol administration. The DEX group was treated with an intraperitoneal injection of 500 mg/kg DEX for five days. On the sixth day, rats were sacrificed and kidney tissues were taken. Histopathological analyses were performed on kidney tissue. Biochemical analyses were performed on kidney tissue and blood to evaluate kidney function and oxidative stress (BUN, creatinine, urea, CK, LDH, cystatin C, TAS, TOS, MDA, and CAT). Additionally, PGC-1α and SIRT-3 gene expression levels in kidney tissue were determined by qRT-PCR. All biomarkers significantly increased in the RM group. DEX treatment significantly reduced urea and creatinine levels. The increase in TOS levels and OSI in the RM group was significant compared to the control group, DEX treatment significantly reversed these effects. The RM and RM + DEX groups exhibited RM and nephropathy. Histopathological analysis revealed improvements in the RM + DEX group compared to the RM group. DEX treatment increased the expression of PGC-1α and SIRT-3 in the RM + DEX group. Histopathological and biochemical improvements, including reduced kidney damage and oxidative stress, were observed with DEX treatment and was associated with increased expression of the PGC-1α and SIRT-3 genes.

Keywords: Acute kidney injury; Dexpanthenol; Oxidative stress; PGC-1α; Rhabdomyolysis; SIRT-3.