Abstract
Tributyltin (TBT) is well known for inducing imposex in mollusks. Studies have shown its hepatotoxicity and immunotoxicity in laboratory animals, with macrophages playing a crucial role in maintaining hepatic homeostasis and influencing disease progression; however, no research has yet explored its effects on hepatotoxicity and immunotoxicity based on hepatic macrophages. To address this gap, weaned rats were treated with corn oil or TBT (0.5, 5, or 50 μg/kg) via oral gavage every three days for 60 days. Liver sections were then subjected to hematoxylin and eosin staining, Oil Red O staining, Sirius Red staining, immunohistochemistry, and immunofluorescence to assess the effects of TBT. Hepatic function and inflammatory state were evaluated by serum biochemistry and quantitative reverse transcription-PCR (qPCR), respectively. Histological examination indicated that TBT exposure did not increase hepatic lipid accumulation but resulted in hepatocyte edema and congestion in the 5 and 50 μg/kg groups, accompanied by progressive hepatic fibrosis. In parallel, 50 μg/kg TBT increased the number of macrophages, driven by an increase in the CD206(+)CD68(+) subset. qPCR analysis revealed a significant decrease in the expression of pro-inflammatory cytokines (such as IL-1β and TNF-α), confirming an immunosuppressive state in the livers of rats exposed to TBT. Moreover, the significant increase in serum ALT activity further revealed hepatic injury induced by 50 μg/kg TBT. In summary, TBT exposure restructures the hepatic immune microenvironment, promoting the progression of liver fibrosis independently of fat accumulation in rats.