It is now apparent that the rate of microsomal drug metabolism in experimental animals is subject to alteration by such dietary deficiencies as protein, vatamins, fats and minerals. The evidence, both published and unpublished, showing the effects of iron, magnesium, and potassium dificiencies on the hepatic metabolism of foreign compounds in rats is discussed. Iron deficiency has been shown to lead to a marked stimulation in hepatic metabolism, in vitro and in vivo, of both Type I (aminopyrine) and Type II (aniline) substrates. Magnesium-deficient rats have been shown to have markedly lower in vivo and in vitro rates of hepatic drug metabolism, but the monovalent intracellular mineral potassium had no apparent effect on the in vitro enzymatic conversion of foreign compounds. Hypokalemia has been shown to alter the in vivo disposition of aminopyrine and pentobarbital as evidenced by an increased plasma half-life of aminopyrine and a longer pentobarbital sleeping time in potassium-deficient animals. Large segments of the world's population are in less than satisfactory nutritional status with respect to iron, magnesium, potassium, copper, and zinc and the relevancy to man of the data discussed must be ascertained. The role of dietary minerals in nonhepatic microsomal drug metabolism is also not yet known.

Aminopyrine N-Demethylase↗

PubMedDate not supplied

Ninety-day toxicity of photomirex in the male rat.

Photomirex (8-monohydromirex) is a demonstrated environmental contaminant and was observed in previous short-term studies to produce lesions in the liver, thyroid and testes of male rats. The present study was undertaken to confirm those observations and to determine the effects after a longer period of exposure. Male rats were fed photomirex for 13 weeks at levels of 0.20, 1.0, 5.0, 25 and 125 ppm in the diet. Deaths were observed in animals receiving the highest dose. Decreased body weight gain and food intake were also observed in that group. Liver weights were increased at 5.0 ppm photomirex and higher. Photomirex caused changes in several biochemical parameters including serum sorbitol dehydrogenase and hepatic aniline hydroxylase activities. Dose-related histological abnormalities were observed in the thyroid and liver starting at the lowest dose level. These results confirm earlier findings and show that photomirex is a potent hepato- and thyrotoxin.

Aniline Hydroxylase↗

PubMedDate not supplied

The absorption, distribution and excretion of photomirex in the rat.

The absorption, distribution, and excretion of photomirex were investigated in the rat. Photomirex was absorbed slowly after oral administration, appeared in the blood at 1.5 hr, and reached the peak concentration 4 hr after dosing. Elimination from the blood was studied in rats receiving single intravenous doses; the semilog-arithmic decay curve was found to be triphasic. The highest concentrations were present in the rat, liver, and skin. Approximately 38--42% of the orally dosed photomirex was excreted in the feces in the first 3 days and 51--55% was eliminated in 28 days. Only trace amounts of photomirex were found in the urine (less than 0.09% of the total dose in 24 hr). Photomirex constituted about 95% of the total radioactivity found in the tissues and feces. No metabolite was detected in the radioactive material extracted from tissues or feces.

Animals↗