Effect of butylated hydroxytoluene and other antioxidants on mouse lung metabolism

Toxic doses of butylated hydroxytoluene (BHT), a phenolic antioxidant commonly used as a food additive, are known to produce lung damage. In this study, 3 days after a single ip injection of 62.5, 215, or 500 mg/kg BHT in mice there was a dose-dependent increase in lung weight. This concentration dependence with injected BHT was accompanied by increases in lung DNA and nonprotein sulfhydryl levels and in whole lung tissue enzyme activities of glutathione (GSH) peroxidase, GSH reductase, glucose-6-phosphate dehydrogenase, and superoxide dismutase. The increased enzyme activities are considered to correspond to inflammatory and proliferative pulmonary changes from acute lung cell injury and necrosis, which have been described previously, and cannot be construed as evidence for a primary oxidant-induced pulmonary lesion. The mechanism of BHT-induced lung changes may not be related to the antioxidant property of BHT, since vitamin E, n-propyl gallate, ethoxyquin, N,N'-diphenylenediamine, and the structurally similar compound, butylated hydroxyanisole did not appear to produce the gross anatomical or biochemical lung changes observed with BHT.