# Exposure to Gulf war illness-related chemicals exacerbates alcohol- induced liver damage in rodents

## TL;DR

Exposure to chemicals linked to Gulf War Illness worsens alcohol-related liver damage in mice, and reducing liver macrophages helps.

## Contribution

This study shows that GWI-related chemicals increase susceptibility to alcohol-induced liver injury in rodents.

## Key findings

- PER/PB exposure caused long-term liver damage and inflammation in mice.
- Prior PER/PB exposure worsened alcohol-induced liver injury, including steatosis and fibrosis.
- Macrophage depletion reduced the exacerbated liver damage in PER/PB-exposed mice.

## Abstract

Gulf War Illness (GWI) describes a series of symptoms suffered by veterans of the Gulf war consisting of cognitive, neurological and gastrointestinal dysfunctions. Two chemicals associated with GWI are the insecticide permethrin (PER) and the nerve gas prophylactic pyridostigmine-bromide (PB). In this study we assessed the effects of PER and PB exposure on pathology and subsequent alcohol (EtOH)-induced liver injury, and the influence of a macrophage depletor, PLX3397, on EtOH-induced liver damage in PER/PB- treated mice. Male C57BL/6 mice were injected daily with vehicle or PER/PB for 10 days, followed by 4 months recovery, then treatment with PLX3397 and a chronic-plus-single-binge EtOH challenge for 10 days. PER/PB exposure resulted in the protracted increase in liver transaminases in the serum and induced chronic low-level microvesicular steatosis and inflammation in GWI vs Naïve mice up to 4 months after cessation of exposure. Furthermore, prior exposure to PER/PB also resulted in exacerbated response to EtOH-induced liver injury, with enhanced steatosis, ductular reaction and fibrosis. The enhanced EtOH-induced liver damage in GWI-mice was attenuated by strategies designed to deplete macrophages in the liver. Taken together, these data suggest that exposure to GWI-related chemicals may alter the liver’s response to subsequent ethanol exposure.