0000000000237584
AUTHOR
Larry W. Robertson
Effect of nutritional imbalances on cytochrome P-450 isozymes in rat liver
Male Sprague-Dawley rats were fed for six weeks either a control diet containing 22% casein (C) and 5% fat (F) or a low-protein diet (6% C, 5% F) or high-lipid diet (30% C, 30% F). A group of rats received a control diet containing 50 ppm of Phenoclor DP6. Three major forms of cytochrome P-450, UT 50, BP 3a and MC 2 were purified from livers of DP6-fed rats and only two forms, UT 50 and PB 3a, were purified from control and dietary groups. The amino acid composition and the catalytic activities towards all substrates tested were only significantly modified in the purified UT 50 P-450 isozyme from rats fed the low-protein diet. The N-terminal sequence analysis shows that cytochrome P-450 UT …
Biphenyl and fluorinated derivatives: liver enzyme-mediated mutagenicity detected in Salmonella typhimurium and Chinese hamster V79 cells.
Abstract Hepatocarcinogenic polychlorinated and polybrominated biphenyls usually show negative results in in vitro mutagenicity assays. Problems in their testing result from their low water solubility and their slow rate of metabolism. We therefore investigated better soluble model compounds, namely biphenyl and its 3 possible monofiuorinated derivatives. In the direct test, these compounds proved tobe nonmutagenic in Salmonella typhimurium TA98 and TA100 (reversion to histidine prototrophy) and in Chinese hamster V79 cells (acquisition of resistance to 6-thioguanine). However, when the exposure was carried out in the presence of NADPH-fortified postmitochondrial fraction of liver homogenat…
Modulation of selenium-dependent glutathione peroxidase by perfluorodecanoic acid in rats: effect of dietary selenium.
Forty-eight male Sprague-Dawley rats fed a diet containing 0.4, 0.2 or 1.0 mg of selenium (Se)/kg of diet were injected with a single dose (35 mg/kg) of perfluorodecanoic acid (PFDA) in corn oil and killed 2 wk later. Control animals were pair-fed and treated with an equal volume of vehicle. PFDA treatment significantly increased Se-dependent glutathione peroxidase (Se-GSHPx) activity in liver cytosol of rats fed the 0.04 mg of Se/kg of diet but not in rats fed the other diets. The increase in liver cytosolic Se-GSHPx activity in rats fed 0.04 mg of Se/kg of diet paralleled increases in Se content and serum Se-GSHPx activity. Determination of Se-GSHPx by an enzyme-linked immunosorbent assay…
Long-term effects of commercial and congeneric polychlorinated biphenyls on ethane production and malondialdehyde levels, indicators of in vivo lipid peroxidation
Ethane exhalation was increased in male Sprague-Dawley rats following a single intraperitoneal (IP) injection of Aroclor 1254 (500 mg/kg). In the first 2 weeks following Aroclor 1254 treatment, the increase in ethane exhalation was due to an inhibition of metabolism of endogenous ethane rather than to an increase in ethane production. In weeks 3 and 4 following Aroclor 1254 administration, metabolic clearance of ethane returned to and exceeded control levels, while ethane production increased to approximately twice the control rates (day 30). The HPLC determination of in situ hepatic malondialdehyde levels revealed a 2-fold increase in malondialdehyde content on day 30 following the Aroclor…
Effect of unbalanced diets on incorporation of δ-aminolevulinic acid into cytochrome P-450
Abstract The in vivo syntheses of two liver microsomal cytochromes P-450 PB 3a , P-450 UT 50 [(1987) Eur. J. Biochem., submitted] ( M r 50 000, 52 000) have been estimated by measuring the specific activity 2 h after i.p. administration of δ-[ 3 H]aminolevulinic acid to male Sprague Dawley rats. The animals were fed either a standard rat chow (5% lard, 22% casein) or unbalanced diets (high lipid, 30% lard or low protein, 6% casein) with or without 50 ppm Phenoclor DP6. The high-lipid diet supported a more rapid body weight gain but had little impact on cytochrome P-450 content, expressed either per whole liver or per mg microsomal protein, and on the incorporation of the precursor into cyto…
A time course investigation of vitamin A level and lipid composition of the liver endoplasmic reticulum in rats following treatment with congeneric polychlorobiphenyls.
Abstract The drug metabolizing enzyme activities, the vitamin A content and the fatty acid composition in the endoplasmic reticulum membrane were studied in rat liver after a single injection of the polychlorobiphenyls (PCBs) 3,3′,4,4′-tetrachlorobiphenyl [(3,4)2Cl] or 2,2′,4,4′,5,5′-hexachlorobiphenyl [(2,4,5)2Cl], 300 μ mol/kg each. The microsomal vitamin A level was markedly lowered 3 days after treatment with (3,4)2Cl, a coplanar type inducer of cytochrome P-450. A marked increase in microsomal AHH and UDPGT activities occurred within 3 days after injection of (3,4)2Cl whereas (2,4,5,)2Cl treatment enhanced APDM activity only. Arachidonic, stearic and linoleic acid microsomal contents w…