Role of amifostine in preventing liver injury caused by paracetamol intoxication

This investigation attempted to examine the possible protective impact of amifostine, alone or in combination with N-acetylcysteine (NAC), in paracetamol-induced liver injury. Fifty-six adult male Wistar rats (weighing 180–200 g) were randomly divided into seven groups (n = 8 per group): sham, paracetamol, amifostine, NAC, paracetamol + NAC, paracetamol + amifostine, and paracetamol + NAC + amifostine. Liver injury was assessed through serum AST and ALT activities, tissue glutathione and nitric oxide (NO) levels, and histopathological scoring. Severe hepatocellular injury was detected only in the paracetamol + NAC group. The paracetamol + NAC + amifostine group exhibited significantly lower hepatocyte damage compared with both paracetamol + NAC and paracetamol + amifostine groups, ranking second only to the control group. Mild to moderate regenerative changes were noted in the livers of the paracetamol + NAC and paracetamol + amifostine groups. No signs of fibrosis, iron storage, or steatosis were detected in any experimental group. Tissue NO levels were lowest in the paracetamol + NAC + amifostine group, reaching statistical significance compared to all other groups. The combined administration of amifostine and NAC provided superior protection against paracetamol-induced liver injury compared with standard NAC therapy, supporting the potential role of amifostine as an adjunct treatment.