Trans-sodium crocetinate attenuates acute kidney injury induced by rhabdomyolysis in rats: focusing on PI3K/AKT, apoptosis, and autophagy pathways.

Abstract

Rhabdomyolysis (RM) is a clinical disorder characterized by the release of potentially toxic muscle cell components into the bloodstream, with acute kidney injury (AKI). Trans-sodium crocetinate (TSC) is derived from the carotenoid crocetin known for its renoprotective, anti-inflammatory, and antioxidant properties. This study aimed to assess the protective effects of TSC on RM-induced AKI in rats. Six groups of rats (n = 6) were used: control, AKI (50% glycerol 10 mL/kg, intramuscularly), AKI treated with TSC (10, 20, and 40 mg/kg, intraperitoneally), and TSC (40 mg/kg) alone groups. Two days after the initial injection, urine and blood samples were collected over 24 h to investigate creatine phosphokinase (CPK), kidney function markers, and electrolyte levels. Additionally, kidney tissue was collected to assess renal oxidative markers, histological alterations, and the expression of protein markers related to autophagy, apoptosis, renal injury, inflammation, and the PI3K/AKT signaling pathway. After glycerol administration, there was an increase in oxidative stress, autophagy, apoptosis, renal injury, and inflammatory marker levels, accompanied by a decrease in the proteins of the PI3K/AKT signaling pathway in the kidney. The co-administration of TSC with glycerol resulted in the improvement of renal dysfunction and structural abnormalities, achieved through a reduction in oxidative stress. TSC also down-regulated autophagy, apoptotic, renal injury, and inflammatory markers. Furthermore, TSC treatment led to a decrease in the renal expression of PI3K/AKT signaling pathway proteins. In conclusion, TSC exhibited a protective effect against RM-induced AKI by modulating oxidative stress, autophagy, apoptosis, and the PI3K/AKT pathway.