Investigation of the Effects of Silymarin and Vitamin C on Kidney Damage and Aquaporin-2 Downregulation in Lithium-Induced Nephrogenic Diabetes Insipidus in Rats

Abstract

Abstract While lithium (LIT) therapy is widely regarded as the primary approach for managing bipolar disorder over the long term, it is also a major contributor to the development of acquired Nephrogenic Diabetes Insipidus (NDI) with prolonged use. This study aimed to examine the protective effects of Silymarin, Vitamin C, and the combined administration of SIL + Vit C against nephrotoxicity induced by NDI resulting from long-term LIT treatment in rats. The groups of rats exposed to LIT were provided with 1 kg of regular commercial chow containing an 80 mmol LiCl supplement for 28 days. Meanwhile, SIL and Vit C were orally administered to rats at a dosage of 200 and 100 mg/kg body weight, respectively, throughout the 28 days. Both the levels of reactive oxygen species (ROS) glutathione (GSH) and malondialdehyde (MDA) were assessed and enzyme activities of superoxide dismutase (SOD) were assessed to determine the protective effect of SIL and Vit C against oxidative stress. Aquaporin-2 (AQP2) levels in kidney tissues were evaluated immunohistochemically and by ELISA method to determine the anti-downregulatory effect. In addition, serum and urine parameters were measured. Lithium-induced nephrotoxicity was characterized by elevated levels of renal toxicity markers and reduced antioxidant enzyme activities. Administration of SIL significantly reduced kidney tissue toxicity markers, increased antioxidant enzyme activities, regulation of physiological parameters in blood and urine, and downregulation of AQP2 in the kidney. However, no significant protective effect against lithium-induced renal toxicity was observed with the administration of Vitamin C. These findings indicate that SIL effectively guards against lithium-induced nephrotoxicity, whereas Vitamin C does not possess this protective effect.