Tributyltin Alters Hepatic Immune Microenvironment to ProMote Liver Fibrosis Progression in Rats.

Area of Science:

• Environmental toxicology
• Immunology
• Hepatology

Background:

• Tributyltin (TBT) is a known endocrine disruptor causing imposex in mollusks.
• Previous studies indicate TBT's hepatotoxicity and immunotoxicity in animals.
• The role of hepatic macrophages in TBT-induced liver damage remains unexplored.

Purpose of the Study:

• To investigate the effects of TBT on hepatotoxicity and immunotoxicity, focusing on hepatic macrophages.
• To determine if TBT-induced liver fibrosis is associated with lipid accumulation.
• To elucidate TBT's impact on the hepatic immune microenvironment.

Main Methods:

• Weaned rats were orally administered TBT (0.5, 5, or 50 μg/kg) or corn oil for 60 days.
• Liver tissues were analyzed using H&E, Oil Red O, Sirius Red staining, and immunohistochemistry.
• Hepatic function and inflammation were assessed via serum biochemistry and qPCR.

Main Results:

• TBT exposure led to hepatocyte edema, congestion, and progressive liver fibrosis in a dose-dependent manner.
• TBT increased macrophage populations, specifically the CD206+CD68+ subset, at higher doses.
• TBT suppressed pro-inflammatory cytokine expression (IL-1β, TNF-α) and increased serum ALT levels, indicating liver injury.

Conclusions:

• TBT exposure induces liver injury and fibrosis in rats independent of hepatic lipid accumulation.
• TBT restructures the hepatic immune microenvironment, promoting immunosuppression and fibrosis progression.