The Role of Systemic Inflammation in Paracetamol Poisoning-An Experimental Model.

Accumulating evidence indicates that acute, life-threatening acetaminophen (APAP) poisoning is associated with systemic inflammation (SI). Investigating SI in experimental models holds promise for the development of pathogenetic therapies. This study aimed to evaluate SI manifestations in a murine model of APAP-induced toxic liver injury. Ten-week-old male C57Bl/6 mice received a single intraperitoneal dose of 600 mg/kg APAP, corresponding to the median lethal dose (LD50). To assess signs of multiorgan damage and SI, we performed histological examinations of internal organs as well as immunoenzymatic, hematological, and biochemical analyses of blood samples. Histological analysis revealed tissue alterations in the liver, kidneys, spleen, lungs, and heart, accompanied by functional impairment. Statistically significant changes were observed in plasma levels of tumor necrosis factor-α (TNF-α), IL-1α, IL-6, IL-10, C-reactive protein (CRP), platelet count, total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and troponin I. Severe liver damage induced by APAP was associated with a cytokine storm, coagulopathy (thrombocytopenia), systemic alterations, pulmonary edema, and multiorgan dysfunction. Collectively, these findings indicate that severe APAP-induced liver damage triggers SI as a characteristic pathological process.