Effects of pregnancy on the cytochrome P-450 system in mice

Lambert, George H.; Lietz, Helen; Kotake, Alvin N.

doi:10.1016/0006-2952(87)90495-3

Cited by 7 publications

(4 citation statements)

References 25 publications

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“…Pregnancy is known to decrease the overall content of the constitutive P450 isozymes in rats and mice 25,30) The present study shows that pregnancy appeared to exert a negative effect on cytochrome P450 content at a late stage, whereas microsomal protein content showed little change during pregnancy. Pregnancy also decreased the rate of formation of styrene glycol, to which CYP2E1 contributed more than CYP2C11/6.…”

Section: Discussionsupporting

confidence: 43%

Effects of Pregnancy, Age and Sex in the Metabolism of Styrene in Rat Liver in Relation to the Regulation of Cytochrome P450 Enzymes

Kishi¹,

Sata²,

Katakura³

et al. 2005

Journal of Occupational Health

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To elucidate the effect of maternal styrene exposure, which is due to various postnatal changes in the development and behavior of offspring, we investigated pregnancy-induced changes in the metabolism of styrene in rat liver in relation to the regulation of cytochrome P450 enzymes. We also examined age and sex-induced changes in the metabolism of styrene. Pregnancy appeared to exert a negative effect on cytochrome P450 content at the late stage, whereas microsomal protein content showed little change during pregnancy. Pregnancy significantly decreased the rate of formation of styrene glycol at the late stage. The percentage of remaining activity in microsomes exposed to anti-CYP2E1 was lower than that exposed to anti-CYP2C11/6 in pregnant and non-pregnant female rats and immature male rats, indicating that CYP2E1 contributes to the metabolism of styrene more than CYP2C11/6 in these rats. Although pregnancy seemed to decrease styrene metabolism, the contribution of CYP2E1 seemed to be slightly increasing. In conclusion, pregnancy clearly influences the metabolism of styrene as well as other characteristic factors such as age and sex. It is very important to elucidate the changes in specific P450 isozyme composition related to their characteristic modification and in their affinity for chemicals.

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Section: Discussionsupporting

confidence: 43%

Effects of Pregnancy, Age and Sex in the Metabolism of Styrene in Rat Liver in Relation to the Regulation of Cytochrome P450 Enzymes

Kishi¹,

Sata²,

Katakura³

et al. 2005

Journal of Occupational Health

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“…While they are comparable to human tissue levels, the PCB 95 tissue levels in the present study were significantly lower compared to levels observed previously in PCB 95-treated adult female mice (see Table 3A, Supporting Information). Pregnancy-associated changes in lipid and lipoprotein disposition − explain, at least in part, differences in the disposition of PCB 95 between pregnant vs nonpregnant mice. Briefly, endogenous lipids and PCB 95 are mobilized from adipose tissue during lactation and, ultimately, eliminated via the breast milk .…”

Section: Discussionmentioning

confidence: 99%

“…In addition to differences in the internal dose, pregnancy-associated physiological changes, such as changes in P450 enzyme composition − and/or lipid disposition, may contribute to small differences in the OH-PCB metabolite profile and/or the chiral signatures of PCB 95 and its metabolites. For example, changes in the hepatic P450 enzyme composition have been shown to alter OH-PCB profiles in in vitro metabolism studies , and affect chiral signatures of other chiral environmental pollutants, such as chlordanes. , Several animal studies have shown that physiological changes during pregnancy alter the enantioselective disposition of chiral bronchodilators or antidepressants .…”

Section: Discussionmentioning

confidence: 99%

Effect of Pregnancy on the Disposition of 2,2′,3,5′,6-Pentachlorobiphenyl (PCB 95) Atropisomers and Their Hydroxylated Metabolites in Female Mice

Kania-Korwel

Barnhart

Lein

et al. 2015

Chem. Res. Toxicol.

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Chiral PCBs, such as PCB 95, are developmental neurotoxicants that undergo atropisomeric enrichment in non-pregnant, adult mice. Because pregnancy is associated with changes in hepatic cytochrome P450 enzyme activity as well as lipid disposition and metabolism, this study investigates the effect of pregnancy on the maternal disposition of chiral PCBs. Female C57Bl/6 mice (8 weeks old) were dosed daily beginning 2 weeks prior to conception and continuing throughout gestation and lactation (56 days total) with racemic PCB 95 (0, 0.1, 1.0 or 6.0 mg/kg body wt/day) in peanut butter. Levels and chiral signatures of PCB 95 and its hydroxylated metabolites (OH-PCBs) were determined in adipose, blood, brain and liver. Tissue levels of PCB 95 increased 4 to 12 fold with increasing dose, with considerable enrichment of the second eluting atropisomer in all tissues (EF range 0.11 to 0.26). OH-PCBs displayed atropisomeric enrichment in blood and liver, but were not detected in adipose and brain. Levels of PCB 95 and its metabolites were 2 to 11 fold lower in pregnant dams relative to those previously reported in non-pregnant age-matched female mice; however, PCB 95 and OH-PCB profiles and chiral signatures were similar between both studies. In contrast, human brain samples contained racemic PCB 95 residues (EF=0.50). These results demonstrate that changes in cytochrome P450 enzyme activity and lipid disposition during pregnancy reduce the PCB body burden in dams, but do not affect metabolite profiles or chiral signatures. The differences in chiral signatures between mice and humans suggest species-specific differences in atropisomeric disposition, the toxicological significance of which remain to be determined.

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“…47 Expression of cytochrome CYP2B1/2 phosphatidylcholine to phosphatidylethanolamine, the latter of which stimulates the hydroxylation of some xenobiotics. The decrease in total P450 content and inhibition of the P450-dependent metabolism of xenobiotics observed in pregnancy [42], may reduce the risk associated with the generation of active metabolites. Further studies revealed that pregnancy (like other physiological factors such as age, sex and lactation) is associated with changes in the rat liver pattern of P450 isoforms; for example, CYP2E1 and CYP2C11/6 levels decrease slightly in pregnancy, and CYP1A1/2, and CYP2B1/2 levels remain unchanged [43].…”

Section: Nonpregnant Ratsmentioning

confidence: 99%

Expression of cytochrome CYP2B1/2 in nonpregnant, pregnant and fetal rats exposed to tobacco smoke.

Czekaj¹,

Wiaderkiewicz²,

Florek³

et al. 2000

Acta Biochim Pol

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Four-month-old female Wistar rats were exposed for 20 days to tobacco smoke obtained from non-filter cigarettes. During the exposure, concentration of tobacco smoke was monitored indirectly by measuring the CO level (1500 mg/m 3 air). The efficacy of exposure was assessed by measuring urine nicotine and cotinine levels. Cigarette smoke did not change total cytochrome P450 and b 5 protein levels in any of the organs studied, and most of these organs did not show any changes in the activity of reductases associated with these cytochromes. Following exposure to tobacco smoke, fetal rat liver expressed CYP2B1/2 protein; in newborns (day 1) both liver and lung showed CYP2B1/2 protein expression and very low pentoxyresorufin O-dealkylase activity. Western blot analysis of adult liver, lung, heart, but not of brain microsomes, showed that tobacco smoke induced CYP2B1/2 in both nonpregnant and pregnant rats, though its expression was lower in the livers and hearts of pregnant females. In the rat and human placenta, neither rat CYP2B1/2 nor human CYP2B6 showed basal or tobacco smoke-induced expression at the protein level. This study shows clearly that the expression of CYP2B1/2, which metabolizes nicotine and some drugs and activates carcinogens, is controlled in rats by age-, pregnancy-, and tissue-specific regulatory mechanisms.The cytochrome CYP2B subfamily inducible by phenobarbital (PB) and other structurally unrelated compounds is widespread in rodents, in contrast to the human orthologous form CYP2B6 that exhibits low expression in liver and extrahepatic tissues and its role is unclear [1]. Both rat liver CYP2B1/2 and human liver CYP2B6 show catalytic activity to-

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Effects of pregnancy on the cytochrome P-450 system in mice

Cited by 7 publications

References 25 publications

Effects of Pregnancy, Age and Sex in the Metabolism of Styrene in Rat Liver in Relation to the Regulation of Cytochrome P450 Enzymes

Effects of Pregnancy, Age and Sex in the Metabolism of Styrene in Rat Liver in Relation to the Regulation of Cytochrome P450 Enzymes

Effect of Pregnancy on the Disposition of 2,2′,3,5′,6-Pentachlorobiphenyl (PCB 95) Atropisomers and Their Hydroxylated Metabolites in Female Mice

Expression of cytochrome CYP2B1/2 in nonpregnant, pregnant and fetal rats exposed to tobacco smoke.

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