Effect of chrysene and carbon tetrachloride administration on rat hepatic microsomal monooxygenase and UDPglucuronosyltransferase activity

Aitio, Antero

doi:10.1016/0014-5793(74)80275-9

Cited by 23 publications

(7 citation statements)

References 26 publications

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“…while the enzyme still remains bound to the membrane. This fully activated form is also found in vivo in severe membrane injury [45,46]. The fully activated form probably resembles the purified enzyme in its regulatory properties.…”

Section: Fac T O Rs A/ffec T Ing Enzyme Activity In Purified and Memmentioning

confidence: 87%

Purification of Rat‐Liver Microsomal UDP‐glucuronyltransferase

Bock

Josting

Lilienblum

et al. 1979

European Journal of Biochemistry

209

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Glucuronidation reactions catalysed by rat liver microsomal UDP-glucuronyltransferase are differentially inducible by 3-methylcholanthrene and phenobarbital. To elucidate the molecular basis of this functional heterogeneity the enzyme was purified from livers of rats pretreated with the inducing agents.Using cholate solubilization, chromatography on Bio-Gel A-1.5m and on DEAE-cellulose in the presence of the nonionic detergent Brij 58, two enzyme forms could be separated. Both forms were subsequently purified to apparent homogeneity by affinity chromatography on UDP-hexanolamine Sepharose 4B. 3-Methylcholanthrene-inducible enzyme activity towards 1-naphthol, 4-nitrophenol, 3-hydroxybenzo(a)pyrene and N-hydroxy-2-naphthylamine copurified with one enzyme form (enzyme 1). In contrast phenobarbital-inducible enzyme activity towards morphine, chloramphenicol and 4-hydroxybiphenyl was associated with the other enzyme fraction (enzyme 2). Sodium dodecylsulfate/polyacrylamide gels showed similar molecular weights of 54000 for enzyme 1 and 56000 for enzyme 2.The results suggest the presence of at least two forms of UDP-glucuronyltransferase in rat liver. Factors affecting enzyme activity in purified and membrane-bound states are discussed.

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Section: Fac T O Rs A/ffec T Ing Enzyme Activity In Purified and Memmentioning

confidence: 87%

Purification of Rat‐Liver Microsomal UDP‐glucuronyltransferase

Bock

Josting

Lilienblum

et al. 1979

European Journal of Biochemistry

209

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“…The increased UDPG transferase of lungs seems to be in part due to low food consumption whereas that of liver may be solely attributed to membrane damage. Carbontetrachloride induced liver injury has been reported to result in increased UDPG transferase activity (15) which is attributed to the liver damage thereby resulting in the release of this enzyme (32,33).…”

Section: Discussionmentioning

confidence: 99%

Drug metabolism in experimental tuberculosis: I. Changes in hepatic and pulmonary monooxygenase activities due to infection

Batra

Venkitasubramanian

Raj

1987

European Journal of Drug Metabolism and Pharmacokinetics

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Pulmonary and hepatic drug metabolizing enzyme activities of tuberculous guinea pigs were examined in detail. Experimental tuberculosis resulted in enlargement of liver and lung accompanied by decreased microsomal cytosolic protein. The tuberculosis infection resulted in decreased hepatic contents of cytochrome P-450 and cytochrome b5 NADPH-cytochrome C reductase in lung and liver. A parallel decrease in the microsomal mixed function oxidases (MFO) was observed in liver and lung of tuberculous guinea pigs. The hepatic and pulmonary activities of UDP-glucuronyl transferase were elevated in the infected animals. Glutathione S-transferase activity exhibited an increase in liver and decrease in the lung of tuberculous guinea pigs. Some of the changes observed in monooxygenase in tuberculosis were caused by reduced food consumption. In general, tuberculosis infection can be viewed to lower drug metabolizing capacity of the animal, probably due to the damage and disturbed membrane integrity.

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“…Carbon tetrachloride is metabolized by the monooxygenase complex to active intermediates (Recknagel 1967;Slater & Sawyer 1971;Aitio 1974;Sipes et a/. 1977) which disturb the microsomal membrane integrity possibly by causing lipid peroxidation (Recknagel & Ghoshal 1966;Glende et al 1976;Masuda & Murano 1977) 1967;Sasame et al 1968;Aitio 1974;Vainio & Parkki 1974) and activate UDPglucuronosyltransferase (Aitio 1974). The activating effect of carbon tetrachloride on the activity of microsomal monooxygenase complex and UDPglucuronosyltransferase has been explained by the location of the enzymes in the membrane (Aitio 1974).…”

mentioning

confidence: 99%

“…1977) which disturb the microsomal membrane integrity possibly by causing lipid peroxidation (Recknagel & Ghoshal 1966;Glende et al 1976;Masuda & Murano 1977) 1967;Sasame et al 1968;Aitio 1974;Vainio & Parkki 1974) and activate UDPglucuronosyltransferase (Aitio 1974). The activating effect of carbon tetrachloride on the activity of microsomal monooxygenase complex and UDPglucuronosyltransferase has been explained by the location of the enzymes in the membrane (Aitio 1974). Pretreatment of rats with phenobarbital potentiates the effects of carbon tetrachloride (Sasame er al.…”

mentioning

confidence: 99%

Differences in the Response of Hepatic and Intestinal Drug Metabolizing Enzymes in Rats Following Carbon Tetrachloride and/or Phenobarbital Treatment

Koivusaari

Lang

Hietanen

1980

Acta Pharmacologica et Toxicologica

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The activities of the microsomal drug metabolizing enzymes in the liver and intestinal mucosa of rats were studied after the intraperitoneal administration of carbon tetrachloride and/or subcutaneous phenobarbital administration. The membrane phospholipid content was decreased after carbon tetrachloride treatment indicating destruction in the membrane structure. Aryl hydrocarbon hydroxylase activity was decreased in the liver and intestinal mucosa after treatment with CCl4 alone and in combination with phenobarbital. The CCl4 treatment increased the intestinal epoxide hydratase activity but decreased the activity in the liver. The hepatic UDPglucuronosyltransferase was slightly induced by phenobarbital and the activity was elevated by the CCl4 treatment. In the intestinal mucosa the enhanced UDPglucuronosyltransferase activity was observed only after phenobarbital pretreatment and the activity was decreased by CCl4. These results support the view that epoxide hydratase and UDPglucuronosyltransferase enzymes occupy different locations in the endosplasmic reticulum of intestinal mucosa than of liver.

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Effect of chrysene and carbon tetrachloride administration on rat hepatic microsomal monooxygenase and UDPglucuronosyltransferase activity

Cited by 23 publications

References 26 publications

Purification of Rat‐Liver Microsomal UDP‐glucuronyltransferase

Purification of Rat‐Liver Microsomal UDP‐glucuronyltransferase

Drug metabolism in experimental tuberculosis: I. Changes in hepatic and pulmonary monooxygenase activities due to infection

Differences in the Response of Hepatic and Intestinal Drug Metabolizing Enzymes in Rats Following Carbon Tetrachloride and/or Phenobarbital Treatment

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