THE EFFECT OF SELENIUM AND VITAMIN E DEFICIENCY ON THE TOXICITY OF NITROFURANTOIN IN THE CHICK

Publisher Summary This chapter discusses the effect of selenium and vitamin E deficiency on the toxicity of nitrofurantoin in chick. Nitrofurantoin (N-[5–nitro–2–furfurylidine]–l–amino–hydantoin) is a commonly used urinary tract antimicrobial drug. It has been implicated in a number of drug-induced toxicities, the most common of which is associated with pulmonary injury. Recent studies suggest that the acute toxicity of this drug is mediated by an oxidative stress resulting from the futile reductive metabolism of the drug. In the study described in the chapter, the nitro compound is reduced to the nitro aromatic anion free radical, which is, then, re-oxidized by molecular oxygen regenerating the parent compound and forming superoxide. Superoxide, then, disproportionates to form hydrogen peroxide and ultimately the hydroxyl radical. One line of defense for the aerobic organism against these activated forms of oxygen is the selenium dependent glutathione peroxidase. The chapter explains that the toxicity of nitrofurantoin in the 10–12 day old chick is increased by decreasing the activity of this enzyme. In this animal model, it is found that vitamin E affords no protection against the toxicity of this nitro drug. Data supports the hypothesis that the toxicity of nitrofurantoin in vivo is because of activated forms of oxygen.