Comparative evaluation of the efficacy of prophylactic administration of ademetionine and an oxymethyluracil-n-acetylcysteine complex in thioacetamide-induced toxicity

Objective - To conduct a comparative evaluation of the efficacy of prophylactic correction using ademetionine and a complex of oxymethyluracil with N-acetylcysteine in a model of thioacetamide-induced toxicity. Materials and Methods. The study was performed on 56 male rats. Toxicity was induced by intraperitoneal administration of thioacetamide at 50 mg/kg body weight twice weekly for 100 days. The animals were assigned to four groups: negative control, positive control, and two experimental groups receiving thioacetamide in combination with either ademetionine or the oxymethyluracil-N-acetylcysteine complex. The corrective agents were administered one hour prior to the toxicant. On days 50 and 100, serum and urine biochemical parameters were assessed, along with gene expression in the liver and kidneys related to antioxidant defense, the glutathione system, apoptosis, and the cell cycle. Histological and morphometric tissue analyses were also performed. Results. The positive control group confirmed the development of chronic toxic hepatitis with progressive liver fibrosis. The use of a complex of oxymethyluracil and acetylcysteine demonstrated superiority over ademetionine in preventing long-term outcomes, with ademetionine primarily exerting an early metabolic effect without affecting the progression of liver fibrosis or structural tissue remodeling in the later stages. Regarding the kidneys, morphometric stress was observed by the end of the treatment period, most noticeable in the positive control group and during prophylactic administration of ademetionine. Conclusion. Under the conditions of intoxication considered, both compounds demonstrated a certain ability to modify late structural outcomes. The complex compound of oxymethyluracil with acetylcysteine demonstrated a more favorable profile at the late stage, while ademetionine was more effective at the early stages. These findings highlight the potential of antioxidant-targeted strategies for the prevention of adverse outcomes in chronic toxic injury.