N-acetylcysteine+nimesulide: An association strategy aiming to prevent nimesulide-induced hepatotoxicity

Introduction: Nimesulide is a potent anti-inflammatory with rapid and long-lasting effects, but also with a high risk of hepatotoxicity. Objective: This work aimed to prevent nimesulide-induced hepatotoxicity through the association of nimesulide with a hepatoprotective agent. Materials and Methods: First, we tested three hepatoprotective agents: N-acetylcysteine, L-carnitine, and Gingko biloba extract in an in vitro hepatic cell model. Both N-acetylcysteine and G. biloba showed promisor results. We selected N-acetylcysteine to continue the studies in an animal model. In vivo study was performed using male Wistar rats divided in 4 groups: control, nimesulide (100mg/kg/day), nimesulide (100mg/kg/day) + N-acetylcysteine (100mg/kg/day) and N-acetylcysteine alone (100mg/kg/day). Treatments were given by gavage, daily, for 15 days. Results: Animals receiving nimesulide alone showed lower body weight gain compared to control. Body weight gain in the nimesulide + N-acetylcysteine group was higher than nimesulide alone, evidencing lower toxicity. However, the body weight gain of the nimesulide + N-acetylcysteine group was still lower than the control animals. Animals treated with nimesulide alone presented an increased relative mass of heart, liver, and spleen and significant hepatic damage seen in microscopy when compared to other groups. N-acetylcysteine co-administered with nimesulide prevented the increased heart mass, but the same was not true with liver and spleen. Conclusions: This work evidence partial protection elicited by the association of N-acetylcysteine and nimesulide against nimesulide-induced hepatotoxicity.