Constitutive and Inducible Hepatic Cytochrome P450 Isoforms in Senescent Male and Female Rats and Response to Low-Dose Phenobarbital

2003 ◽  
Vol 31 (5) ◽  
pp. 612-619 ◽  
Author(s):  
Arun K. Agrawal ◽  
Bernard H. Shapiro
Keyword(s):  
Cytochrome P450 ◽  
Low Dose ◽  
Female Rats ◽  
Male And Female ◽  
Male And Female Rats ◽  
Cytochrome P450 Isoforms ◽  
Hepatic Cytochrome

scholarly journals Intrasplenic Transplantation of Isolated Adult Rat Hepatocytes

2011 ◽  
Vol 40 (1) ◽  
pp. 83-92 ◽  
Author(s):  
Meena R. Sharma ◽  
Wojciech Dworakowski ◽  
Bernard H. Shapiro
Keyword(s):  
Cytochrome P450 ◽  
Adult Male ◽  
Total Concentration ◽  
Rat Hepatocytes ◽  
Female Rats ◽  
Female Rat ◽  
Male And Female ◽  
Sexual Dimorphisms ◽  
Male And Female Rats ◽  
Male Specific

Adult male and female rat hepatocytes were individually transplanted into the spleens of adult male and female rats. The recipients were euthanized at either eight, sixteen, thirty, or forty-five weeks following transplantation, at which time hepatic and splenic levels of liver-specific rat albumin mRNA as well as sex-dependent transcript levels of CYP2C11, -2C12, -2C7, -2A1, and -3A2—which accounts for > 60% of the total concentration of hepatic constituent cytochrome P450—were determined. Whereas the pre-infused hepatocytes expressed their expected cytochrome P450 sexual dimorphisms (female-specific CYP2C12, male-specific CYP3A2, and female-predominant CYP2A1), their post-transplantational competence now reflected the sexual dimorphisms of the recipient (as observed in the host’s liver), which supports the concept that the sex-dependent growth hormone circulating profiles are the determinants regulating the expression levels of hepatic cytochrome P450. Also expressed at normal concentrations in the pre-infused hepatocytes, male-specific CYP2C11 and female-predominant CYP2C7 were inexplicably undetectable in the spleens of both recipient males and females, regardless of the sex of the donor hepatocytes, almost one year after transplantation.

Effect of dexamethasone treatment on the biotransformation of glyceryl trinitrate: cytochrome P450 3A1 mediated activation of rat aortic guanylyl cyclase by glyceryl trinitrate

1994 ◽  
Vol 72 (12) ◽  
pp. 1513-1520 ◽  
Author(s):  
Bernard J. McDonald ◽  
Greg J. Monkewich ◽  
Patrick G. Long ◽  
Diane J. Anderson ◽  
Paul E. Thomas ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Glyceryl Trinitrate ◽  
Guanylyl Cyclase ◽  
Female Rats ◽  
Male Rats ◽  
Male And Female ◽  
Treated Male ◽  
Cyclase Activation ◽  
Male And Female Rats ◽  
Hepatic Microsomes

It is generally accepted that organic nitrates act via vascular biotransformation to an activator of guanylyl cyclase (presumably NO), resulting in increased cyclic GMP accumulation and vascular smooth muscle relaxation. Previously, we have shown that cytochrome P450 can mediate the biotransformation of glyceryl trinitrate (GTN) and that at least a portion of this biotransformation results in the formation of an activator of guanylyl cyclase. To assess the role of the cytochrome P450 3A subfamily in this phenomenon, we treated male and female rats with dexamethasone (DEX) (150 mg/kg, i.p., daily for 3 days). Under anerobic conditions, hepatic microsomal biotransformation of GTN was increased three-fold in DEX-treated male rats compared with all other treatment groups. Incubation of aortic 100 000 × g supernatant fraction from untreated rats (as a source of guanylyl cyclase) with GTN and hepatic microsomes from all groups resulted in concentration-dependent increases in guanylyl cyclase activation. Microsomes from DEX-treated male and female rats demonstrated a significantly greater activation of guanylyl cyclase compared with microsomes from untreated males and females. Furthermore, GTN-induced guanylyl cyclase activation mediated by microsomes from DEX-treated male and female rats was markedly inhibited by a polyclonal antibody raised to rat CYP3A1. Since CYP3A2 is absent or very low in hepatic microsomes from DEX-treated adult female rats, this identifies CYP3A1 as an isoform capable of biotransforming GTN to an activator of guanylyl cyclase. Similarly, CYP2C11 was identified as an isoform capable of biotransforming GTN to an activator of guanylyl cyclase, since monoclonal antibody to CYP2C11 inhibited GTN-induced activation of guanylyl cyclase mediated by microsomes from control male rats. In both male and female rats, DEX treatment had no effect on GTN-induced relaxation of isolated aorta. However, biotransformation of GTN in intact aorta from DEX-treated male rats was decreased. This suggests that DEX treatment affects only the aortic biotransformation of GTN that is not involved in the formation of an activator of guanylyl cyclase.Key words: glyceryl trinitrate, dexamethasone, guanylyl cyclase, cytochrome P450, vasodilation, biotransformation.

Low dose effects of BPA on early sexual development of male and female rats

2013 ◽  
Vol 41 ◽  
pp. 11 ◽  
Author(s):  
Sofie Christiansen ◽  
Marta Axelstad ◽  
Julie Boberg ◽  
Ulla Hass
Keyword(s):  
Sexual Development ◽  
Low Dose ◽  
Female Rats ◽  
Male And Female ◽  
Male And Female Rats ◽  
Dose Effects ◽  
Low Dose Effects

scholarly journals Low-dose effects of bisphenol A on early sexual development in male and female rats

Reproduction ◽  
2014 ◽  
Vol 147 (4) ◽  
pp. 477-487 ◽  
Author(s):  
Sofie Christiansen ◽  
Marta Axelstad ◽  
Julie Boberg ◽  
Anne Marie Vinggaard ◽  
Gitte Alsing Pedersen ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Sexual Development ◽  
Low Dose ◽  
Dose Range ◽  
Daily Intake ◽  
Reproductive Organ ◽  
Female Rats ◽  
Male And Female ◽  
Male And Female Rats ◽  
Pregnancy And Lactation

Bisphenol A (BPA) is widely detected in human urine and blood. BPA has been reported to impair many endpoints for reproductive and neurological development; however, it is controversial whether BPA has effects in the microgram per kilogram dose range. The aim of the current study was to examine the influence of BPA on early sexual development in male and female rats at dose levels covering both regulatory no observed adverse effect levels (NOAELs) (5 and 50 mg/kg bw per day) as well as doses in the microgram per kilogram dose range (0.025 and 0.25 mg/kg bw per day). Time-mated Wistar rats (n=22) were gavaged during pregnancy and lactation from gestation day 7 to pup day 22 with 0, 0.025, 0.25, 5 or 50 mg/kg bw per day BPA. From 0.250 mg/kg and above, male anogenital distance (AGD) was significantly decreased, whereas decreased female AGD was seen from 0.025 mg/kg bw per day and above. Moreover, the incidence of nipple retention in males appeared to increase dose relatedly and the increase was statistically significant at 50 mg/kg per day. No significant changes in reproductive organ weights in the 16-day-old males and females and no signs of maternal toxicity were seen. The decreased AGD at birth in both sexes indicates effects on prenatal sexual development and provides new evidence of low-dose adverse effects of BPA in rats in the microgram per kilogram dose range. The NOAEL in this study is clearly below 5 mg/kg for BPA, which is used as the basis for establishment of the current tolerable daily intake (TDI) by EFSA; thus a reconsideration of the current TDI of BPA appears warranted.

Ethylbenzene-mediated induction of cytochrome P450 isozymes in male and female rats

1992 ◽  
Vol 44 (6) ◽  
pp. 1171-1182 ◽  
Author(s):  
David J. Sequeira ◽  
Charles S. Eyer ◽  
George F. Cawley ◽  
Todd G. Nick ◽  
Wayne L. Backes
Keyword(s):  
Cytochrome P450 ◽  
Female Rats ◽  
Male And Female ◽  
Male And Female Rats ◽  
P450 Isozymes ◽  
Cytochrome P450 Isozymes

Abstract 515: Central Angiotensin (ang) (1-7) Inhibits the Sensitizing Effects of a Low Dose Ang Ii in Hypertension Produced by a Subsequent Slow Pressor Dose of Ang Ii in Male and Female Rats

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
BAOJIAN XUE ◽  
Fang Guo ◽  
Meredith Hay ◽  
Alan K Johnson
Keyword(s):  
Low Dose ◽  
Pressor Response ◽  
Protective Role ◽  
Female Rats ◽  
Ang Ii ◽  
Central Administration ◽  
Male And Female ◽  
Male And Female Rats ◽  
Sensitization Process ◽  
Pre Treatment

Previous studies using an Induction-Delay-Expression (I-D-E) experimental design demonstrated that pre-treatment with ANG II for 1 week produces a sensitized hypertensive response to subsequent ANG II administration in males but not in females. In this sensitization process, several brain renin-angiotensin-aldosterone system components including angiotensin converting enzyme 2 (ACE2) expressions were enhanced. It has been shown that ANG (1-7), formed from ANG II by ACE2, plays an anti-hypertensive role in the central nervous system. The present study tested whether central ANG (1-7) protects against the sensitizing effects of a low dose of ANG II. Male and female rats were implanted for telemetered blood pressure (BP) recording. During I low doses of ANG II alone or with concurrent icv administration of ANG (1-7) or its antagonist A-779 were given for 1 week. After a 1 week rest ( D ), a slow pressor dose of ANG II was given for 2 weeks ( E ). In males, the low dose of ANG II during I resulted in an enhanced pressor response to the subsequent slow pressor dose of ANG II given during E in comparison to those rats receiving vehicle during I (Δ42.8±7.2 vs Δ21.2±5.3 mmHg). Central administration of ANG (1-7) during I blocked the low dose ANG II-induced sensitization (Δ16.4±4.0 mmHg). In contrast, the low dose of ANG II did not sensitize the hypertensive response in females to the subsequent slow pressor dose of ANG II (Δ13.0±5.4 vs Δ9.9±3.4 mmHg). Central blockade of ANG (1-7) by icv infusion of A-779 during I resulted in sensitization by the low dose of ANG II (Δ26.7±2.0 mmHg) in females. The results indicate that ANG (1-7) plays a protective role during the sensitization process, especially in females, and its administration can attenuate the development of ANG II-induced hypertension in both male and female.

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