Loss of haem in rat liver caused by the porphyrogenic agent 2-allyl-2-isopropylacetamide

Matteis, Federico De

doi:10.1042/bj1240767

Cited by 185 publications

(54 citation statements)

References 22 publications

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“…Therefore, it appears possible that both PCB and secobarbital induce the enzyme which metabolizes retinoic acid to deactivated metabolite, resulting in the reduction of hepatic vitamin A content. Secobarbital causes a destruction of the hepatic microsomal cytochrome P-450 heme, and its mechanism is suggested that secobarbital is converted to an active metabolite such as epoxide by the hepatic microsomal mixed function oxidase system, leading to the destruction of cytochrome P-450 heme (27,28). It is also suggested that this destruction of cytochrome P-450 heme is unrelated to lipid peroxidation (29).…”

Section: Discussionmentioning

confidence: 99%

Effect of the degradation of cytochrome P-450 heme by secobarbital on polychlorinated biphenyls (PCB)-induced hepatic vitamin A reduction and lipid peroxide formation in rats.

Saito

Ikegami

Aizawa

et al. 1983

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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SummaryThe present studies were conducted to characterize the relevance of a microsomal mixed function oxidase system to the polychlo rinated biphenyls (PCB)-induced vitamin A reduction and endogenous lipid peroxide formation in the liver of rats. And also, this study dealt with an influence of scavengers on the hepatic lipid peroxide formation stimulated by PCB. Rats were given a 0.01% PCB diet supplemented with adequate nutrients, for 14 days. In an experiment, secobarbital was injected subcutaneously for the degradation of hepatic microsomal cy tochrome P-450 heme. A marked liver enlargement and a significant increase of total liver lipid content were observed in the PCB group. The secobarbital enhanced the PCB-induced liver enlargement but no effect of secobarbital on the lipid content was recognized. PCB significantly induced hepatic microsomal cytochrome P-450, but not both cytochrome b5 and NADPH-cytochrome c reductase. The secobarbital suppressed the induction of cytochrome P-450 caused by PCB to approximately one-half. The hepatic vitamin A content significantly decreased on PCB adminis tration and the secobarbital slightly enhanced the PCB-induced vitamin A reduction. However, the vitamin A content in the secobarbital-injected control group decreased to nearly the same levels as in the PCB groups. Therefore, it was presumed that the hepatic microsomal mixed function oxidase system, especially the cytochrome P-450, was possibly not directly involved in the PCB-induced hepatic vitamin A reduction or that a metabolic system related to mixed function oxidase system was involved in 1 Polychlorinated biphenyls toxicity and nutrition . XVI. Polychlorinated biphenyls toxicity and vitamin A (8).* To whom all correspondence should be addressed. the reduction. On the other hand, the hepatic lipid peroxide content tended to increase on PCB administration though no significant difference was recognized. In contrast, the hepatic lipid peroxide content signi ficantly increased in the secobarbital-injected PCB group as compared with the secobarbital-injected control group. However , there was no difference in the lipid peroxide contents between the control groups with and without the injection of secobarbital , and also between the PCB groups. The hepatic vitamin E contents lowered in the secobarbital injected groups but no effect was observed on PCB administration . The glutathione peroxidase activity decreased significantly on PCB adminis tration and the secobarbital further decreased the activity . Therefore, it was suggested that the significant increase and tendency of increase in hepatic lipid peroxide contents in the PCB groups with and without injection of secobarbital were ascribed to an insufficiency of lipid peroxide scavengers in the liver. And also, it was supposed that the degradation of hepatic microsomal cytochrome P-450 heme caused by secobarbital was not responsible for the hepatic lipid peroxide formation on PCB adminis tration, indicating that the cytochrome P-450 was possibly not directly involved...

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Section: Discussionmentioning

confidence: 99%

Effect of the degradation of cytochrome P-450 heme by secobarbital on polychlorinated biphenyls (PCB)-induced hepatic vitamin A reduction and lipid peroxide formation in rats.

Saito

Ikegami

Aizawa

et al. 1983

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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“…The formation of "green pigments" during administration of 2-allyl-2-isopropylacetamide was shown by De Matteis to be due to destruction of P450 (De Matteis, 1971). Ethylene and other olefins were found to have similar destructive properties (Ortiz de Montellano and Mico, 1980).…”

Section: Biotransformationmentioning

confidence: 94%

The Development of Drug Metabolism Research as Expressed in the Publications of ASPET: Part 2, 1959–1983

Murphy¹

2008

Drug Metab Dispos

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ABSTRACT:In 25 years, drug metabolism research went from using subcellular particles of undefined content to an understanding of metabolism at the molecular level. The discoveries of cytochrome P450, enzyme induction, reactive intermediates, and genetic polymorphisms were milestones in the field. New publications from the American Society for Pharmacology and Experimental Therapeutics chronicled the discoveries and provided communications to advance the science of drug metabolism.

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“…This mitochondrial enzyme catalyses the initial step of the haem biosynthetic pathway and is the decisive controlling factor for overall rate of haem synthesis in the liver (Marver & Schmid, 1972). The activity of this enzyme appears to be regulated by the end product of the pathway, haem, and for this reason a regulatory 'pool' of hepatic haem has been postulated (De Matteis, 1971;Tschudy & Bonkowsky, 1972;Meyer & Schmid, 1973;Watson, 1975). The precise mechanisms of this regulation remains controversial (Scholnick, Hammaker & Marver, 1969;Sassa & Granick, 1970;Hayashi, Kurashima & Kikuchi, 1972), although evidence for its existence has come from various studies.…”

Section: Discussionmentioning

confidence: 99%

Hepatic Drug Metabolism and Haem Biosynthesis in Lead‐poisoned Rats

Goldberg

Meredith

Miller

et al. 1978

British J Pharmacology

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1 Pretreatment of rats with intraperitoneal injections of lead was shown to result in a depression of the microsomal mixed function oxidase system, as assessed by a decrease in hepatic microsomal P-450 and b5 content and by a decrease in the activity of the enzymes aniline hydroxylase and aminopyrine demethylase. Lead had a more marked effect on cytochrome P-450 than b5. 2 The activity of the rate-limiting enzyme of haem biosynthesis, c-aminolaevulinic acid synthase, was inversely correlated with the microsomal cytochrome P-450 content. 3 The activity of the haem biosynthetic enzymes 6-aminolaevulinic acid dehydratase, coproporphyrinogen oxidase and ferrochelatase were decreased by increasing lead pretreatment. 4 The activity of the haem catabolic enzyme, haem oxygenase, was increased by lead pretreatment. IntroductionIt has long been recognized that haem synthesis in man is severely affected by increased body lead burden. This inhibition of haem production is well known to result in decreased levels of circulating haemoglobin in lead-exposed individuals. The possibility of altered drug metabolism due to inhibition of synthesis of the microsomal haemoprotein cytochrome P-450 has been the subject of a number of studies both in man and animals.Recent reports (Alvares, Kapelner, Sassa & Kappas, 1975; Meredith, Campbell, Moore & Goldberg, 1977)

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Loss of haem in rat liver caused by the porphyrogenic agent 2-allyl-2-isopropylacetamide

Cited by 185 publications

References 22 publications

Effect of the degradation of cytochrome P-450 heme by secobarbital on polychlorinated biphenyls (PCB)-induced hepatic vitamin A reduction and lipid peroxide formation in rats.

Effect of the degradation of cytochrome P-450 heme by secobarbital on polychlorinated biphenyls (PCB)-induced hepatic vitamin A reduction and lipid peroxide formation in rats.

The Development of Drug Metabolism Research as Expressed in the Publications of ASPET: Part 2, 1959–1983

Hepatic Drug Metabolism and Haem Biosynthesis in Lead‐poisoned Rats

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