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J Bazare

Publications and source records attributed to J Bazare.

3 recordsLinked to original sources

Effects of aging and caloric restriction on hepatic drug metabolizing enzymes in the Fischer 344 rat. I: The cytochrome P-450 dependent monooxygenase system.

The effects of long-term caloric restriction on the hepatic cytochrome P-450 dependent monooxygenase system were investigated in the 22-month-old Fischer 344 rat. Caloric restriction decreased the age-related changes in hepatic testosterone metabolism, which are associated with demasculinization of the liver. Caloric restriction also increased hepatic microsomal testosterone 6 beta-hydroxylase, lauric acid 12-hydroxylase and 4-nitrophenol hydroxylase activities over corresponding values in both ad libitum fed 22-month and 60-day-old control male rats. This suggests that cytochrome P-450 isozymes, P-450 pcn1&2, P-452 and P450j may be induced by caloric restriction. Such changes in cytochrome P-450 isozyme profiles could result in altered carcinogen activation, radical formation or drug detoxication in the calorically restricted rat.

Aging↗

Effects of aging and caloric restriction on hepatic drug metabolizing enzymes in the Fischer 344 rat. II: Effects on conjugating enzymes.

The effects of long-term caloric restriction on the hepatic phase II drug metabolizing enzymes were investigated in the male Fischer 344 rat. Rats that had been restricted to 60% of their pair-fed control consumption from 14 weeks post-partum exhibited altered conjugating enzyme activities at 22 months. Caloric restriction significantly reduced the age-related decrease in glutathione-S-transferase activity towards 1,2-dichloro-4-nitrobenzene, but did not significantly alter the age-related changes in UDP-glucuronyltransferase or sulfotransferase activities towards hydroxysteroids. Caloric restriction appeared to increase hepatic microsomal UDP-glucuronyltransferase activity toward bilirubin and gamma-glutamyltranspeptidase activities. These observations suggest that caloric restriction has multiple effects on the hepatic phase II drug metabolizing enzymes in the rat. Such effects may alter hepatic metabolism and activation or detoxification of drugs and carcinogens.

Aging↗

Sampling methods for pharmacokinetic studies in the mouse.

Pharmacokinetics data on 2,4,5-T are used to illustrate design considerations, agent administration and sampling techniques required for single-animals studies in mice. Detailed methods for intravenous and intragastric delivery of chemicals are described, as are small volume (3 microliters) blood sampling techniques from tail vein and orbital plexus. A mouse metabolism cage is described that prohibits feed contamination of urine and feces, and also effectively segregates these elimination products. Techniques for blood, urine, and feces sample preparation and quality control assessments are also presented. Multi-sample blood concentration-time curves obtained from a single mouse are compared to data obtained using a single-sample design using may mice. While a single-animal, multiple-sample design requires the availability of microanalytical methods, it has many economic and practical advantages and results in a more accurate pharmacokinetic profile of the chemical in mice.

2,4,5-Trichlorophenoxyacetic Acid↗