Protective role of boron on hepatotoxicity and oxidative stress induced by trichloroacetic acid

Abstract

Abstract We conducted a comprehensive investigation into the protective roles of boron (B) against trichloroacetic acid (TCA)-induced hepatotoxicity by assessing TCA exposure in vivo and exploring the potential mechanisms by which B protects against TCA-induced hepatotoxicity in vitro. For the in vivo study, we evaluated TCA-induced hepatotoxicity in adult male B6C3F1 mice exposed to 25, 50, 125, and 500 mg/kg/day of TCA, respectively, for 21 days. We found that the mice’s liver weight was significantly increased, and that there were changes in hepatic histopathology, particularly in mice treated with the highest dosage (500 mg/kg/day). TCA also increased the hepatic oxidoreductase activity of medium-chain and long-chain acyl-coenzyme A (CoA), which are biomarkers of peroxisome proliferation, in a dose-dependent manner. Subsequently, we established a TCA-induced HepG2 cell model of oxidative damage to estimate the cytotoxicity and determine the positive effects of B administration in vitro. We found that B administration significantly reduced oxidative stress by attenuating the production of TCA-induced reactive oxygen species and malondialdehyde. B also significantly downregulated the concentrations of certain cytokines, including interleukin (IL)-6, IL-8, and transforming growth factor-beta, which are predominantly associated with the p38 mitogen-activated protein kinase (MAPK) signaling pathway. In addition, B significantly upregulated phospho-p38 levels and downregulated Bax and p21 levels in the cytoplasm and downregulated p38 and p21 levels in the nucleus. Taken together, our findings suggest that the protective role of B against TCA-induced hepatotoxicity primarily involves alleviation of oxidative damage and cell apoptosis caused by TCA and might be mediated via the p38 MAPK pathway.

Keywords

• Trichloroacetic acid
• Boron
• Hepatotoxicity
• Oxidative damage
• p38 MAPK pathway