Vitamin D Ameliorates Oxidative and Inflammatory Effects of Hepatorenal Injury of Acute Paracetamol Toxicity: An experimental study

Abstract

Introduction and aim: An accidental or intentional paracetamol overdosage is a common condition, with hepatic injury as a common complication. Kidney could be injured in association with hepatic injury. Prevention and/or proper treatment is markedly important. The current study aimed to investigate the role of vitamin D (VD) in acute paracetamol-induced hepatorenal damage. Methodology: Fourty male Wister rats were divided into 4 equal groups. The negative control (NC), the positive control (PC) (received paracetamol 1200mg/kg), prophylactic group (received VD (1000 IU/Kg/day) before induction of toxicity and treatment continued after induction); and the treatment group with VD (2000 IU/Kg/day) for five successive days after induction of toxicity, for three successive cycles. VD levels, serum liver enzymes, total protein, albumin, serum urea and creatinine were estimated. The concentrations of interferon-γ (IFN- γ), interleukins (IL1β, IL4, IL10, and IL-17) in the tissue lysate were determined. The oxidative stress indicators and antioxidant enzymes (glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH) and Malonaldehyde (MDA)) were also measured. Results: Liver enzymes, serum urea and creatinine were increased in PC than NC groups, and were significantly reduced in prophylactic and treatment groups. But not return normal values, and prophylactic group is better. Total proteins and albumin significantly reduced by paracetamol toxicity and returned to near normal with VD supplementation.  Vitamin-D levels were significantly reduced in PC than NC groups. However, it was significantly increased in prophylactic and treatment groups than NC and PC groups. IFN- γ, IL-1β, IL-17, and MDA were significantly increased, while IL-10, GPx, CAT, and GSH were significantly reduced in PC than NC groups. Prophylactic and treatment groups improved the values. However, SOD significantly reduced in PC than NC group. Vitamin D was significantly and inversely correlated with ALT, AST, ALP, albumin, creatinine, liver and kidney IFN-γ, IL-1β, IL-17 and MDA. But, it was proportionately and significantly correlated with liver and kidney IL-10. Conclusion: Acute paracetamol toxicity alters hepatic and renal VD homeostasis through oxidative stress and pro-inflammation. Vitamin D supplementation had an ameliorative action on hepatorenal injury, and the long duration of VD supplementation had better outcome.