Alcohol administration induces oxidative stress, which is defined as a disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. The primary result of oxidative stress is the increase in the steady state concentration of reactive oxygen species including hydrogen peroxide. Many processes and factors are involved in causing alcohol-induced oxidative stress, including redox state changes as a result of ethanol and acetaldehyde oxidation, acetaldehyde generation and acetaldehyde adduct formation, mitochondrial damage and decreased ATP production, Kupffer cell activation via increases in endotoxin levels, and induction of cytochrome P450 2E1 (CYP2E1). In this work, the specific role of hydrogen peroxide on ethanol-induced oxidative stress was explored using transgenic mice that overexpress catalase, an enzyme that catalyzes the dismutation of hydrogen peroxide into molecular oxygen and water. Transgenic mice overexpressing catalase and wild-type controls were administered orally for four weeks an isocaloric liquid diet such that 0% or 36% of energy was contributed by ethanol. The redox state of the GSH/GSSG was used as an indicator of oxidative stress. The redox state of the GSH/GSSG pair was determined by measuring the concentrations and the ratios of the main interconvertible reduced (GSH) and oxidized (GSSG) forms of glutathione. The hepatic level of total glutathione and the GSH/GSSG ratio were significantly lower in ethanol-treated wild-type mice than in control wild-type mice, reflecting hepatic oxidative stress conditions induced by chronic ethanol. Overexpression of catalase in transgenic mice prevented the effect of ethanol on total glutathione and the GSH/GSSG ratio. These results suggest that hydrogen peroxide plays a central role in the development of hepatic alcohol-induced oxidative stress.

Effect of catalase overexpression on ethanol-induced oxidative stress in mice

249th National Meeting (2015)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.