High mobility group box1 as a danger signal inducing the infiltration of neutrophils and macrophages in thioacetamide-induced rat liver injury

Abstract

The liver, a major organ involved in substance metabolism, is highly susceptible to toxicity induced by chemicals and their metabolites. Although damage-associated molecular patterns (DAMPs) have been implicated in the development of sterile inflammation following cell injury, their involvement in chemically induced hepatocellular injury remains underexplored. This study aimed to determine the role of high-mobility group box 1 (HMGB1), a DAMP, in a rat model of liver injury treated with thioacetamide, a hepatotoxicant. The rats were administered thioacetamide and treated with HMGB1 neutralizing antibody. Histopathological analysis revealed the absence of significant differences between control rats and HMGB1 neutralizing antibody-treated rats. However, HMGB1 neutralizing antibody-treated rats showed a reduction in the hepatic devitalization enzymes, a decrease in the number of anti-inflammatory cluster of differentiation 163⁺ M2 macrophages and neutrophils in the injured area, and a decrease in cytokine expression. These results suggest that HMGB1 leads to the progression of inflammation after chemically induced hepatocyte injury and may represent a therapeutic target for mitigating such injury.