D-Ribose-L-Cysteine Mitigates Hepato-Renal Dysfunction in a STZ + HFD Rat Model of Diabetes

Abstract

Introduction: Diabetes mellitus is a major global health concern often associated with oxidative stress–induced organ complications, particularly in the liver and kidneys. D-ribose-L-cysteine (DRLC), a cysteine prodrug and glutathione precursor, has been suggested as a potential antioxidant therapy. This study investigated the ameliorative effects of DRLC on hepato-renal dysfunction in HFD-fed, andStreptozotocin (STZ)-induced diabetic rats.Materials and Methods: Male Wistar rats were randomly assigned to five groups. For 28 days, the experimental groups were treated orally with either HFD+STZ, metformin (100 mg/kg), or DRLC at doses of 150 mg/kg and 300 mg/kg. Biochemical parameters, including oxidative stress biomarkers, liver function indices like Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), AspartateAminotransferase (AST), and Gamma-Glutamyl Transferase (GGT), renal markers, proteins (albumin, total protein, globulin), and electrolytes were evaluated.Results: HFD+STZ significantly increased MDA, MPO, NO, liver enzymes, creatinine, urea, and bilirubin, while markedly reducing SOD, CAT, GSH, GST, GPx, albumin, globulin, total protein, and electrolytes (p < 0.05), indicating hepato-renal dysfunction. These alterations were significantly mitigated (p<0.05) following DRLC treatment, with effects comparable to metformin. DRLC decreased prooxidant biomarkers, enhanced antioxidant defense, normalized serum proteins, and restored electrolyte balance.Conclusion: DRLC effectively attenuated oxidative stress and improved liver and kidney function in HFD+STZ-induced diabetic rats, suggesting its therapeutic potential as an antioxidant-based intervention against diabetes-associated organ complications.