Sorbitol induces sub-chronic nephrotoxicity via escalating JAK1/STAT3, oxidative stress and inflammation in Sprague Dawley rats

Sorbitol (SOR) is a natural food sweetener that is widely used in candies, chocolates, biscuits, and jams. SOR showed toxic impacts on different body organs except renal tissues. Therefore, the present investigation was conducted to assess the sub-chronic nephrotoxic effects of SOR on renal tissue. Thirty-six Sprague Dawley rats were apportioned into control, SOR (20 mg/kg), SOR (45 mg/kg) and SOR (90 mg/kg) treated group. SOR intoxication showed upregulation in the gene expression of JAK1, STAT3, NF-κB, TNF-α, IL-18, IL-6, IL-1β, and COX-2. The levels of ROS and MDA were promoted while the enzymatic activities of HO-1, SOD, GPx, GSR, CAT and GST were reduced after SOR administration. SOR exposure showed elevation in the levels of cystatin C, BUN, KIM-1, urea, creatinine, uric acid, NAG, while a reduction in creatinine clearance in dose-dependent manners. Besides, SOR intoxication escalated the levels of Caspase-9, Caspase-3 and Bax while reducing the levels of Bcl-2. Moreover, SOR administration distorted the renal histology at all the tested doses. These findings suggest the nephrotoxic effects of SOR in dose-dependent manners as 90 mg/kg > 45 mg/kg > 20 mg/kg owing to its pro-oxidative, pro-inflammatory and pro-apoptotic attributes.