Effects of Ascorbic Acid Deficiency on Kinetics of Drug Hydroxylation in Male Guinea Pigs

Abstract

The effects of ascorbic acid (vitamin C) deficiency on components of drug-hydroxylating systems in guinea pig liver were investigated. Although the liver weight-body weight ratio was increased, the concentration of microsomal protein was markedly less in ascorbic acid-deficient guinea pigs. This was reflected in a decrease in aniline and hexobarbital hydroxylation reactions when calculated on a unit of liver weight; however, when analyzed per unit of microsomal protein, ethylmorphine demethylase activity was unaffected. The Km's for these substrates, as well as the ethyl isocyanide difference spectra, were unchanged, indicating that no qualitative changes had occurred in the enzymes responsible for their metabolism or in the cytochrome P-450. Aniline metabolism per unit protein was depressed by ascorbic acid deficiency, as was the content of cytochromes P-450 and b5. The return of function by a single injection of ascorbic acid given 1-24hr. prior to decapitation was not frequently observed. Induction with sodium phenobarbital was not blocked by this dietary deficiency state.