The induction of hepatic microsomal metabolism in rats following acute administration of a mixture of polybrominated biphenyls

Dent, John G.; Netter, K.J.; Gibson, James E.

doi:10.1016/0041-008x(76)90132-0

Cited by 124 publications

(28 citation statements)

References 28 publications

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“…7-ethoxyresorufin-(2 AM), 7-methoxyresorufin-(5 AM), and 7-benzyloxyresorufin (5 AM) O-dealkylase activities were assayed fluorometrically using 0.2-0.3 mg protein and measuring the amount of the released resorufin as detailed by Re et al (1993). The activity of 7-ethoxycoumarin O-deethylase was determined using 0.2-0.4 mg protein and 0.8 mM substrate concentration as reported by Dent et al (1976). The rate of benzo(a)pyrene (0.2 mM) hydroxylation was measured as reported elsewhere (Nebbia et al, 1996) and the hydroxylation of aniline (5 mM) was assayed with about 1 mg protein by measuring the amount of 4-aminophenol formed .…”

Section: Cyp-dependent Monooxygenase and Microsomal Carboxylesterase mentioning

confidence: 99%

Postnatal development of hepatic oxidative, hydrolytic and conjugative drug-metabolizing enzymes in female horses

2004

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Section: Cyp-dependent Monooxygenase and Microsomal Carboxylesterase mentioning

confidence: 99%

Postnatal development of hepatic oxidative, hydrolytic and conjugative drug-metabolizing enzymes in female horses

2004

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“…They cause a mixed-type induction similar to that caused by treatment with both phenobarbital (PB) and 3-methylcholanthrene (MC) (6)(7)(8).…”

Section: Introductionmentioning

confidence: 96%

Studies on the Microsomal Metabolism and Binding of Polybrominated Biphenyls (PBBs)

Dannan¹,

Moore²,

Aust³

1978

Environmental Health Perspectives

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The metabolism of polybrominated biphenyls (PBBs) was studied in vitro by using rat liver microsomes in the presence of NADPH and atmospheric 02. Quantitative recoveries of all PBBs were obtained after incubations with control or 3-methylcholanthrene (MC) induced microsomes. Of the twelve major components, losses of only peaks I (2,4,5,2',5'-pentabromobiphenyl) and 3 (a hexabromobiphenyl) were observed following incubations with microsomes from phenobarbital (PB)-or PBBs-pretreated rats. Of seven structurally identified PBB components, only peak 1 has a bromine-free para position. Peaks 1, 2, and 5 all have two adjacent unsubstituted carbons, yet only peak I is metabolized. Of two dibromobiphenyl model compounds studied, the 2,2'-congener was very rapidly metabolized by PB-induced microsomes whereas its 4,4'-isomer was not. These results suggest that the presence of a free para position is required for the metabolism of brominated biphenyls. Of lesser importance appears to be the number of bromines or the availability of two adjacent unsubstituted carbons. In vivo evidence for the metabolism of peaks 1 and 3 was also provided by their drastically diminished levels in liver and milk extracts. When a '4C-PBB mixture consisting almost exclusively of peaks 4 (2,4,5,2',4',5'-hexabromobiphenyl) and 8 (2,3,4,5,2'4',5'-heptabromobiphenyl) was incubated with PB-or PBBs-induced microsomes and NADPH, only traces of radioactivity remained with the microsomes after extensive extraction. However, less radioactivity was bound to microsomes from MC pretreated or especially control rats. No radioactivity was bound to exogenous DNA included in similar microsomal incubations, regardless of the type of microsomes used. Under the same conditions, [3H]-benzo[a]pyrene metabolites were bound to DNA, and PBB-induced microsomes enhanced this binding more than six-fold.

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“…Polybrominated biphenyls stimulate hepatic microsomal mixed function oxygenases in adult rats and mice (6,7,20 (22). Thus, since AHH activity is increased while EH activity is decreased (adults) or not affected (immature rats) in kidney following treatment with PBBs, subsequent administration of a compound metabolized by these enzymes may result in increased concentrations of arene oxides and possibly amplified nephrotoxicity.…”

Section: Discussionmentioning

confidence: 99%

“…These observations suggest that renal function may be impaired by PBBs. When administered acutely or subchronically, PBBs increase the activity of hepatic drug metabolizing enzymes in rats (6,7). Stimulation of hepatic microsomal enzymes following PBBs is similar to that observed after treatment with both phenobarbital (PB) and 3-methylcholanthrene (3MC) (6), two compounds which represent cytochrome P450 and P-450 inducing agents, respectively (8). Currently, there is a scarcity of information regarding PBBs effects on the activity of extrahepatic microsomal enzymes.…”

Section: Introductionmentioning

confidence: 92%

Effects of Polybrominated Biphenyls on Kidney Function and Activity of Renal Microsomal Enzymes

McCormack¹,

Kluwe²,

Sanger³

et al. 1978

Environmental Health Perspectives

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Polybrominated biphenyls (PBBs) cause hepatic microsomal enzyme stimulation and histopathological alterations in several organs, including kidney. Concern about effects of PBBs on the health of newborns has increased after the discovery of PBBs in milk of nursing mothers. Therefore, it was of interest to investigate the effects of PBBs on kidney function and the activity of renal microsomal enzymes in adult and immature animals. Seven and eleven day old pups were treated with a single IP injection of either peanut oil or 150 mg/kg PBBs (FireMaster BP-6) in peanut oil. Adult virgin rats were fed diet containing 0 or 100 ppm PBBs for 30 or 90 days. Treatment with PBBs only retarded weight gain after 90 days exposure. Kidney-to-body weight ratio was not altered by PBBs. Arylhydrocarbon hydroxylase activity was increased while epoxide hydratase activity was decreased (adults) or not affected (immature rats) in kidney following treatment with PBBs. Administration of PBBs had no effect on blood urea nitrogen, the clearance of inulin, p-aminohippurate (PAH), or fractional sodium excretion. Similarly, the in vitro accumulation of PAH and N-methylnicotinamide (NMN) by thin renal cortical slices and ammoniagenesis and gluconeogenesis in renal cortical slices were not affected by PBBs. In conclusion, treatment with PBBs resulted in modification of the activity of renal microsomal enzyme activities but had no detectable effect on renal function.

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The induction of hepatic microsomal metabolism in rats following acute administration of a mixture of polybrominated biphenyls

Cited by 124 publications

References 28 publications

Postnatal development of hepatic oxidative, hydrolytic and conjugative drug-metabolizing enzymes in female horses

Postnatal development of hepatic oxidative, hydrolytic and conjugative drug-metabolizing enzymes in female horses

Studies on the Microsomal Metabolism and Binding of Polybrominated Biphenyls (PBBs)

Effects of Polybrominated Biphenyls on Kidney Function and Activity of Renal Microsomal Enzymes

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