RESUMO
A study of the effects of butylated hydroxyanisole (BHA) on the hepatic metabolism was conducted with emphasis on parameters linked to energy metabolism and mitochondrial reactive oxygen species production. The experimental systems were the isolated perfused rat liver and isolated mitochondria. It was found that BHA inhibits biosynthetic pathways (gluconeogenesis) and ammonia detoxification, which are dependent on ATP generated within the mitochondria. Conversely, the compound stimulated glycolysis and fructolysis, which are compensatory phenomena for an inhibited mitochondrial ATP generation. Furthermore, BHA diminished the cellular ATP content under conditions where the mitochondrial respiratory chain was the only source of this compound. Inhibition of gluconeogenesis started at the concentration of 50 µM and was generally pronounced at concentrations under 200⯵M. Several effects, however, were prominent only at the concentrations of 500 and 750⯵M. BHA can be considered, thus, a mild metabolic agent that becomes toxic only at high doses. An aggravating factor could be the observation that BHA exerts a net stimulating action on reactive oxygen species (ROS) production in isolated mitochondria, an observation that contradicts the general notion that the compound acts primarily as an antioxidant. Considerable time was required for the reversion of most effects after removal of the compound from the circulation. In toxicological terms, besides the lack of circulating glucose, one can expect metabolic acidosis due to excess lactate production, impairment of ammonia detoxification and cell damage due to a deficient maintenance of its homeostasis and possible excessive ROS production.
