Hepatic cytochrome P-450 in rats submitted to chronic hypobaric hypoxia

1990 ◽  
Vol 259 (4) ◽  
pp. C654-C659 ◽  
Author(s):  
L. E. Costa
Keyword(s):  
Hypobaric Hypoxia ◽  
Female Rats ◽  
Adaptation To Hypoxia ◽  
Simulated Altitude ◽  
Male And Female Rats ◽  
Group 3 ◽  
Liver Homogenates ◽  
Cytochrome P 450 ◽  
Hepatic Cytochrome ◽  
Group 1

Hepatic cytochrome P-450 content in adaptation to hypobaric hypoxia was studied in three groups of rats and in their respective controls at sea level atmospheric pressure. The experimental groups were as follows: 1) young male and female rats submitted to 4,400 m (simulated altitude) for 6-8 mo, 2) the same animal model of group 1 submitted to 5,500 m (simulated altitude) for a subsequent period of 2-3 mo, and 3) adult males exposed to 5,500 m for 35 days. Hypoxia caused a marked polycythemia in all three groups, body weight loss in males of the three groups and at 5,500 m also in females, whereas liver weight was normal in groups 1 and 2 and slightly decreased in group 3. Cytochrome P-450 content measured in microsomal suspensions of groups 1 and 2 was unchanged. In liver homogenates, cytochrome P-450 content was normal at 4,400 m (group 1) and decreased at 5,500 m (groups 2 and 3). Therefore, endoplasmic reticulum mass, calculated as the ratio of cytochrome P-450 in the homogenates and in the isolated microsomes, was unchanged in group 1 (4,400 m) and decreased in group 2 (5,500 m). The content of antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, measured in liver homogenates of group 3, were markedly decreased (by 40, 30, and 35%, respectively). Results do not support the hypothesis that an increase in cytochrome P-450 content plays a role in adaptation to hypoxia.

scholarly journals Δ9-tetrahydrocannabinol (THC) vapor exposure produces conditioned rewarding effects in male and female rats

2021 ◽  
Author(s):  
Catherine Frances Moore ◽  
Catherine M Davis ◽  
Elise M Weerts
Keyword(s):  
Sex Differences ◽  
Place Preference ◽  
Female Rats ◽  
Place Conditioning ◽  
Exposure Condition ◽  
Male And Female ◽  
Male And Female Rats ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background: Vaping of cannabis and cannabis extracts containing Δ9-tetrahydrocannabinol (THC, the primary psychoactive constituent of cannabis) is on the rise. Development of animal models using vapor exposure is important for increasing our understanding of the rewarding and aversive effects of vaped cannabinoids. Currently there are limited data on the conditioned rewarding effects of THC vapor in rats, and no studies to date examining sex differences. Methods: Male and female Sprague-Dawley rats (N=96; 12 per sex/group) underwent place conditioning after exposure to vaporized THC or vehicle (propylene glycol, PG). THC vapor-conditioned rats received one of three THC vapor exposure amounts (THC Group 1: 5 puffs of 100 mg/ml THC, THC Group 2: 5 puffs of 200 mg/ml THC, or THC Group 3: 10 puffs of 200 mg/ml THC) and matched vehicle vapor (PG) exposure and on alternate days for two sets of 8 daily sessions (16 days total). Vehicle-conditioned rats (Veh Group 0) received only PG vapor exposure each day. Rats were passively administered vapor for 30-min immediately before daily, 30-min conditioning sessions. Untreated rats completed place preference tests after the 8th and 16th conditioning sessions and then testing continued daily until extinction occurred. Following extinction, rats underwent a THC vapor-primed reinstatement session. Results: Male and female rats showed an exposure-dependent preference for the THC vapor-paired chamber, though sex differences were observed. The lowest THC vapor exposure group tested (THC Group 1) did not produce CPP in males or females. Exposure to the middle condition tested (THC Group 2) resulted in preference for the THC vapor-paired chamber in males, but not females. The highest THC vapor exposure condition tested (THC Group 3) produced place preference in both males and females. Preference for the THC-paired chamber extinguished more quickly in males than in females. Following extinction, THC vapor re-exposure (i.e., drug-prime) did not result in reinstatement of place preference for either sex. Conclusion: This study demonstrated conditioned rewarding effects of THC vapor in both male and female rats, and provides evidence for sex differences in doses of THC vapor that produce CPP and in time to extinction. Conditioned place aversion was not observed at any of the THC vapor exposure amounts tested. These data provide a foundation for future exploration of the conditioned rewarding effects vaporized THC, cannabis and its constituents in preclinical models.

scholarly journals Evaluation of Some Male and Female Rats’ Reproductive Hormones Following Administration of Aspartame With or Without Vitamin C or E

2021 ◽  
Vol 45 (2) ◽  
pp. 14-20
Author(s):  
Omar H Azeez
Keyword(s):  
Vitamin C ◽  
Reproductive Hormones ◽  
Female Rats ◽  
Control Group ◽  
Male And Female ◽  
Group 4 ◽  
Male And Female Rats ◽  
Group 3 ◽  
Group 2

Aspartame (ASP) is a sugar substitute. Its use rose because it has been demonstrated to have deleterious effects after being metabolized. In the presence of antioxidant vitamins C or E, the effects of ASP on reproductive hormones of adult male and female Albino Wister rats were investigated. A total of eighty male and female rats were used in this study. The rats were divided into four groups: group 1, received no treatment; group 2, received ASP at 40 mg/kg BW; group 3, received ASP at 40 mg/kg BW with vitamin C at 150 mg/kg BW; and group 4, received ASP at 40 mg/kg BW and vitamin E at 100 mg/kg BW. All treatments were given orally by gavage needle once daily for consecutive 90 days. The levels of estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone hormone (TH) were measured after 90 days in blood plasma. In comparison with the control group, ASP treatment resulted in lower levels of E2, FSH, and LH in male and female rats. When the antioxidants vitamin C or E was given, the effects of ASP were reversed, and the levels of E2, LH, and FSH were increased. The testosterone hormone was likewise significantly increased by ASP, but testosterone hormone concentrations were decreased by vitamin C or E treatments. Long-term ASP consumption caused interfering with testicular and ovarian hormonal activity, while vitamins C and E on the other hand, overcome longstanding consumption ASP's effects.

Aniline and hexobarbital hydroxylases from rat lung and kidney: neither sex dependent nor inducible with phenobarbital

1982 ◽  
Vol 60 (10) ◽  
pp. 1247-1250 ◽  
Author(s):  
Janet L. Lister ◽  
Bruce B. Virgo
Keyword(s):  
Microsomal Protein ◽  
Female Rats ◽  
Rat Lung ◽  
Male And Female ◽  
Aniline Hydroxylase ◽  
Protein Levels ◽  
Male And Female Rats ◽  
Males And Females ◽  
Cytochrome P 450 ◽  
Lung And Kidney

The basal activities of aniline hydroxylase (AH), hexobarbital hydroxylase (HH), and ethylmorphine N-demethylase (ED) were measured in the 9000 × g supernatant of kidneys and lungs from male and female rats. No ED activity was detected in any tissue although all tissues N-demethylated three other substrates. The activities of AH and HH were not sex dependent in either kidney or lung. Similarly, pulmonary and renal microsomal protein concentrations were independent of sex. In addition, cytochrome P-450 levels in the kidney were the same in males and females (pulmonary P-450 was not measured). The pulmonary hydroxylases were more active than the renal enzymes in both sexes. In males, phenobarbital (ip, 50 rng∙kg−1∙day−1 for 3 days) failed to induce AH or HH in either kidney or lung; it did not increase the weight or microsomal protein levels of these organs and it also failed to increase renal P-450. Thus, the basal activities of AH and HH in lungs and kidneys are not different in male and female rats and are not increased by phenobarbital.

Investigation of TAp63 gene Expression and Follicle Count Using Melatonin in Cisplatin-induced Ovarian Toxicity

2020 ◽  
Author(s):  
Hacı Öztürk Şahin ◽  
Mehmet Nuri Duran ◽  
Fatma Sılan ◽  
Ece Sılan ◽  
Duygu Sıddıkoglu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Female Rats ◽  
Histological Evaluation ◽  
Saline Control ◽  
Control Group ◽  
Ovarian Toxicity ◽  
Significant Difference ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Background: Premature ovarian failure is among the most important side effects of chemotherapy during reproductive period. Preserving ovarian function is gradually gaining importance during oncologic treatment. The present study aims to investigate the potential of melatonin to protect from cisplatin-induced ovarian toxicity in rats. Twenty nine female rats were divided to three groups: Saline control group (Group 1), cisplatin group (Group 2), and cisplatin+melatonin group (Group 3). While the rats in Groups 2 and 3 were administered 5 mg/kg single dose of cisplatin via intra-peritoneal (IP) route, the rats in Group 3 were started on melatonin (20 mg/kg IP) before cisplatin administration and continued during 3 consecutive days. Ovaries were removed one week after cisplatin administration in all groups. Blood samples were obtained before the rats were decapited. Histological evaluation, follicle count, and classification were performed. TAp63 mRNA expression was evaluated using mRNA extraction and real-time polymerase chain reaction (PCR) method. Serum estradiol (E2) and anti-mullerian hormone (AMH) values were measured with enzyme immune-assay technology. Results: While primordial follicles were seen to decrease in Group 2 as compared to Group 1 (p:0.023), primordial follicle count was observed to be preserved significantly in melatonin group as compared to Group 2 (p:0.047). Moreover, cisplatin-induced histo-pathological morphology was preserved in favor of normal histology in melatonin group. A significant difference was not observed between groups with regard to mean serum AMH and E2 values (p:0.102 and p:0.411, respectively). While TAp63 gene expression significantly increased in Group 2 as compared to control group (p:0.001), we did not detect a statistically significant difference in cisplatin+melatonin group, although gene expression decreased (p:0.34). Conclusion: We conclude that concurrent administration of melatonin and cisplatin may protect from ovarian damage.

Effect of the anterior pituitary gland and gonads on enzyme components of the hepatic microsomal cytochrome P-450 system of male and female rats

1983 ◽  
Vol 96 (2) ◽  
pp. 259-267 ◽  
Author(s):  
B. Gillham ◽  
J. S. M. Hutchinson ◽  
M. B. Thorn
Keyword(s):  
Sex Difference ◽  
Anterior Pituitary ◽  
Testosterone Propionate ◽  
Specific Activity ◽  
Female Rats ◽  
Intact Male ◽  
Adult Rats ◽  
Microsomal Cytochrome ◽  
Male And Female Rats ◽  
Cytochrome P 450

The concentration of cytochrome P-450 in microsomes prepared from the livers of mature female Wistar-derived rats was significantly lower than in mature males. This sex difference was abolished after hypophysectomy, when the concentration of the cytochrome in males and females was not significantly different from that in the intact male. A concentration of cytochrome P-450 characteristic of females was restored by two anterior pituitary transplants under the kidney capsule of hypophysectomized females; a partial 'feminization' occurred in similarly treated hypophysectomized males. A partial 'feminization' was also achieved by the administration of rat or sheep prolactin to hypophysectomized females. Unexpectedly, the administration of l-dihydroxyphenylalanine to normal females was without effect on cytochrome P-450, whereas in intact males 'feminization' resulted. Castration of adult rats resulted in the 'feminization' of cytochrome P-450, whereas ovariectomy was without effect. Administration of testosterone propionate for 10 days, either immediately after the operation or 14 weeks later to rats castrated when adult failed, however, to reverse the fall in cytochrome P-450. The establishment of a higher concentration of cytochrome P-450 in the liver of female rats could not be brought about by the administration of testosterone propionate, whether given as a single dose on the second day after birth or as a 10-day course of treatment after puberty or both. It is concluded that the sex difference in hepatic microsomal cytochrome P-450 is maintained by the release in the female of an anterior pituitary factor(s) that serves to depress its concentration. The factor(s) shows some of the characteristics of prolactin but the findings are not consistent with that hormone being responsible for all of the effects observed. The release of the factor(s) in the male may be inhibited by a compound of gonadal origin other than testosterone. A sex difference could not be 'imprinted' in the female by either neonatal and/or postpubertal testosterone treatment. The concentration of hepatic microsomal cytochrome b5 and the specific activity of NADPH-cytochrome c reductase were found not to be sex-dependent in the rats used. However, anterior pituitary factor(s) other than prolactin and growth hormone act to suppress partially the concentration of the former and to promote the specific activity of the latter in the endoplasmic reticulum of rat hepatocytes.

scholarly journals Formation of cytochrome P-450 containing haem or cobalt-protoporphyrin in liver homogenates of rats treated with phenobarbital and allylisopropylacetamide

1984 ◽  
Vol 222 (2) ◽  
pp. 453-462 ◽  
Author(s):  
H L Bonkovsky ◽  
J F Sinclair ◽  
J F Healey ◽  
P R Sinclair ◽  
E L Smith
Keyword(s):  
Polyacrylamide Gel Electrophoresis ◽  
Similar Extent ◽  
Factors Affecting ◽  
Cobalt Protoporphyrin ◽  
Liver Homogenates ◽  
Cytochrome P 450 ◽  
Protein Moiety ◽  
Related Compounds ◽  
Insight Into ◽  
Hepatic Cytochrome

The potent porphyrogen allylisopropylacetamide and related compounds decrease hepatic concentrations of cytochrome P-450. This decrease occurs particularly in phenobarbital-induced cytochrome P-450 and is caused by suicidal breakdown of the haem of cytochrome P-450. Quantitative rocket immunoelectrophoresis showed that the protein moiety of the major phenobarbital-inducible form of hepatic cytochrome P-450 was not diminished up to 1 h, but was markedly decreased (to 43% of that of the phenobarbital-treated control) at 20 h after allylisopropylacetamide treatment. In contrast, the concentration of total cytochrome P-450, measured spectrophotometrically, decreased to 30-40% of the control at both 1 and 20 h after allylisopropylacetamide. Cytochrome P-450-dependent demethylations of ethylmorphine and benzphetamine decreased to a similar extent. When liver homogenates from rats treated with allylisopropylacetamide 1 h before being killed were incubated with haem, functional holocytochrome P-450 could be reconstituted from the apoprotein. Incubation with haem increased spectrophotometrically measurable cytochrome P-450 to 69%, ethylmorphine demethylase to 64% and benzphetamine demethylase to 93% of the activities in rats treated with phenobarbital alone. At 20 h after allylisopropylacetamide treatment, however, little or no reconstitution of cytochrome P-450 occurred after incubation with haem. When liver homogenates were incubated with cobalt and protoporphyrin, and microsomal proteins were then subjected to polyacrylamide-gel electrophoresis, cobalt-protoporphyrin was found specifically associated with proteins of Mr 50 000-53 000. When homogenates from rats given allylisopropylacetamide for 1 h or 20 h were compared, it was found that the extent of this association was higher in livers from the rats containing more apocytochrome P-450, suggesting that cobalt-protoporphyrin had associated with the apocytochrome. The data provide insight into the association of haem with the protein moiety of cytochrome P-450 and factors affecting breakdown of this protein.

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