Unimpaired induction of drug-metabolizing enzymes in hepatocytes isolated from rats with micronodular cirrhosis

1991 ◽  
Vol 69 (3) ◽  
pp. 426-436 ◽  
Author(s):  
Zhenqiang Wu ◽  
Daniel Piché ◽  
Sylvie Vallières ◽  
Pierre-Michel Huet ◽  
Marielle Gascon-Barré
Keyword(s):  
Normal Serum ◽  
Female Rats ◽  
Male Rats ◽  
Metabolizing Enzymes ◽  
Mixed Function Oxidase System ◽  
Transformation Potential ◽  
Xenobiotic Biotransformation ◽  
And Control ◽  
Menten Kinetic

To test further the competence of the cirrhotic liver to metabolize xenobiotics, hepatocytes were isolated from control and CCl4-induced cirrhotic male or female rats. Histologically micronodular cirrhosis was present in all CCl4-treated rats, while control rats had normal livers. Portal perfusion pressure and intrahepatic collagen content were also significantly increased by CCl4 administration. In male rats, no significant differences in levels of circulating transaminases nor in alkaline phosphatase was observed between cirrhotic and control rats, while CCl4-treated females had slightly higher than normal serum transaminase levels at the time of the studies. Hepatocytic cytochrome P-450 and basal xenobiotic biotransformation were unaffected by micronodular cirrhosis in both genders; calculation of the aminopyrine and 7-ethoxycoumarin intrinsic clearances (Cli) revealed, however, a slightly decreased transformation potential in hepatocytes obtained from cirrhotic females, a phenomenon not observed in cirrhotic male rats. It is speculated that the observed reduction in Cli may have been independent of cirrhosis per se, owing to the perduring cytotoxic effect of CCl4 as evidenced by the higher than normal level of transaminases in female rats. Finally, male rats were subjected to in vivo administration of phenobarbital or 3-methylcholanthrene; both compounds led to significant induction of the mixed-function oxidase system, which was similar in magnitude and in selectivity in control and cirrhotic rats as illustrated by calculation of the Michaelis–Menten kinetic parameters for aniline p-hydroxylation, aminopyrine-N-demethylation, 7-ethoxycoumarin-O-deethylation, and p-nitrophenol UDP-glucuronyl transferase. We conclude mat in well-established but compensated and hepatolysis-free micronodular cirrhosis, hepatocytes are fully able to transform xenobiotics and to respond normally and selectively to inducers of drug metabolism.Key words: micronodular cirrhosis, hepatocytes, drug metabolism, intact hepatocyte hypothesis, phenobarbital, 3-methylcholanthrene.

Sex as a determining factor in the effect of exercise on in vivo autoimmune response adjuvant arthritis

1994 ◽  
Vol 76 (3) ◽  
pp. 1172-1175 ◽  
Author(s):  
A. Ferry ◽  
C. Le Page ◽  
M. Rieu
Keyword(s):  
Adjuvant Arthritis ◽  
Clinical Signs ◽  
Female Rats ◽  
Male Rats ◽  
Autoimmune Response ◽  
Human Rheumatoid Arthritis ◽  
Control Female ◽  
And Control ◽  
Arthritic Joints

The present study was conducted to examine the effect of physical exercise on the development of adjuvant arthritis (AA), an animal model of the human rheumatoid arthritis, which is a T-cell-dependent autoimmune response. AA was inducted on day 0 in 8-wk-old Lewis rats of both sexes. Between postinjection days 1 and 12, two groups of rats (male and female) were trained on a treadmill every day (45–120 min/day and 15–30 m/min) before the onset of arthritic disease. Trained female (n = 27) and male (n = 22) rats and control female (n = 29) and male (n = 17) rats were observed every 2 days for the following clinical signs of AA: number of arthritic joints (swelling and redness), paw thickness, and weight gain during the disease. The results show that the incidence of arthritis (% of arthritic rats) was significantly higher in trained female rats (74%; P < 0.03) and significantly lower in trained male rats (27%; P < 0.05) compared with control rats of both sexes (female, 45%; male, 59%). There was no difference in the severity and development of the disease between trained rats and control rats of both sexes (P > 0.05). The present study indicates that the effect of exercise on the incidence of AA, an in vivo autoimmune response, depends on the sex of the animal.

CYANOKETONE-INDUCED INHIBITION OF ADRENAL 3β-HYDROXY-Δ5-STEROID OXIDOREDUCTASE ACTIVITY IN FEMALE AND MALE RATS IN VITRO

1976 ◽  
Vol 83 (3) ◽  
pp. 576-582 ◽  
Author(s):  
Sven A. Gustafsson
Keyword(s):  
Sex Differences ◽  
Single Injection ◽  
Female Rats ◽  
Male Rats ◽  
Oxidoreductase Activity ◽  
Control Female ◽  
Lower Affinity ◽  
And Control

ABSTRACT The inhibition of adrenal 3β-hydroxy-Δ5-steroid oxidoreductase activity was studied in vitro 24 h after a single injection of 2α-cyano-4,4,17α-trimethyl-5-androsten-17β-ol-3-one (cyanoketone) to adult castrated female and male rats. The inhibition of conversion of dehydroepiandrosterone1) to androstenedione was about 80 % as compared to adult castrated control rats treated with vehicle only. The conversion of pregnenolone to progesterone and 5α-pregnane-3,20-dione was also inhibited by about 80 % in both sexes. The activity of 3β-hydroxy-Δ5-steroid oxidoreductase was greater both in cyanoketone-treated and control female rats as compared to the corresponding male rats. It is concluded that the previously observed sex differences in response to cyanoketone in vivo are not due to a lower affinity of male adrenal 3β-hydroxy-Δ5-steroid oxidoreductase to cyanoketone.

Effects of in vivo gonadal hormone environment on in vitro hGRF-40-stimulated GH release

1985 ◽  
Vol 249 (3) ◽  
pp. E276-E280 ◽  
Author(s):  
W. S. Evans ◽  
R. J. Krieg ◽  
E. R. Limber ◽  
D. L. Kaiser ◽  
M. O. Thorner
Keyword(s):  
Female Rats ◽  
Male Rats ◽  
Gonadal Hormone ◽  
Base Line ◽  
Pituitary Cells ◽  
Intact Male ◽  
Castrate Male ◽  
Basal Release

The effects of gender and the gonadal hormone environment on basal and stimulated growth hormone (GH) release by dispersed and continuously perifused rat anterior pituitary cells were examined. Cells from intact male and diestrus day 2 female rats and from castrate male rats either untreated or treated with testosterone (T) or 17 beta-estradiol (E2) were used. Basal GH release (ng/min per 10(7) cells; mean +/- SE) by cells from diestrus day 2 female rats was less than by cells from castrate rats treated with T (4.3 +/- 0.6 vs. 11.4 +/- 2.7, respectively; P less than 0.025). No other differences in basal release were detected. Concentration-response relationships were documented between human GH-releasing factor 40 (hGRF-40; 0.03-100 nM given as 2.5-min pulses every 27.5 min) and GH release. Mean (+/- SE) overall GH release (ng/min per 10(7) cells) above base line was greater by cells from intact male rats (496 +/- 92) than by cells from castrate (203 +/- 37.3; P less than 0.0001), castrate and T-treated (348 +/- 52.8; P = 0.008), or castrate and E2-treated (58.1 +/- 6.8; P less than 0.001) male rats or by diestrus day 2 rats (68.6 +/- 9.5; P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals In vivo uptake of [14C]leucine by skeletal muscle ribosomes after injury in rats fed two levels of protein

1969 ◽  
Vol 23 (2) ◽  
pp. 271-280 ◽  
Author(s):  
V. R. Young ◽  
P. C. Huang
Keyword(s):  
Skeletal Muscle ◽  
Specific Activity ◽  
Male Rats ◽  
Thigh Muscle ◽  
Left Femur ◽  
The Right ◽  
And Control ◽  
The Relationship ◽  
In Vivo Uptake

1. After 14 days on a diet containing 5 or 25% casein male rats received a fracture of the left femur. Four hours before they were killed the injured and control rats were injected with [1-14C]leucine; the incorporation of radioactivity into an isolated fraction of skeletal muscle ribosomes was studied 6, 12, 24, 48, 72, 96 and 228 h after injury.2. The incorporation of [14C]leucine into the ribosome fraction in right thigh muscles dropped to 40% of control values 72 h after fracture in well-nourished rats and after 96 h with diets containing 5 or 25%, casein.3. The specific activity of the trichloroacetic acid-soluble fraction of muscle from injured rats was equal to or higher than that of the controls during the first 72 h but lower at 96 h.4. These results suggest that a reduced incorporation of amino acids by ribosomes from the right thigh muscle occurred on day 3 after fracture in the group receiving 25% casein but not in the group receiving 5% casein.5. Muscle RNA and DNA concentrations were not affected by the injury.6. The relationship between these findings and the loss of muscle N after injury is discussed.

Mechanism of increased erythrocyte membrane fluidity during magnesium deficiency in weanling rats

1989 ◽  
Vol 257 (2) ◽  
pp. C270-C276 ◽  
Author(s):  
S. Tongyai ◽  
Y. Rayssiguier ◽  
C. Motta ◽  
E. Gueux ◽  
P. Maurois ◽  
...  
Keyword(s):  
Membrane Fluidity ◽  
Erythrocyte Membrane ◽  
Magnesium Deficiency ◽  
Osmotic Fragility ◽  
Magnesium Content ◽  
Male Rats ◽  
Surface Irregularities ◽  
Erythrocyte Membrane Fluidity ◽  
And Control

The erythrocyte membrane was investigated in weanling male rats pair fed with magnesium-deficient and control diets for 8 days. Fluorescence polarization studies revealed a 15% increase in the fluidity of membranes from deficient rats. A similar increase in the fluidity of liposomes indicated that protein was not involved. The change was associated with decreased osmotic fragility of intact erythrocytes; the cells lost their biconcavity and had a flattened appearance with surface irregularities. Analysis of the membranes showed decreased amounts of magnesium, cholesterol, and sphingomyelin in the deficient group. The reduced ratios of cholesterol to phospholipid and sphingomyelin to phosphatidylcholine were consistent with the increased fluidity. Addition of physiological amounts of magnesium to the medium rigidified membranes incubated in tris(hydroxymethyl)-aminomethane buffer, and this was prevented by the presence of EDTA. Cross-incubation experiments with erythrocyte ghosts and plasma from the two groups of rats showed that magnesium-deficient plasma increased the fluidity of control ghosts and control plasma rigidified ghosts from magnesium-deficient rats. Addition of sufficient magnesium chloride to raise the magnesium content of deficient plasma to normal had no significant effect. These results show that the increased fluidity of the erythrocyte membrane in magnesium deficiency is due to physicochemical exchange with the plasma. Although magnesium can directly influence membrane fluidity, the change during its deficiency in vivo is mainly mediated indirectly via disturbances in lipid metabolism.

Role of estrogens and age in flow-mediated outward remodeling of rat mesenteric resistance arteries

2014 ◽  
Vol 307 (4) ◽  
pp. H504-H514 ◽  
Author(s):  
K. Tarhouni ◽  
M. L. Freidja ◽  
A. L. Guihot ◽  
E. Vessieres ◽  
L. Grimaud ◽  
...  
Keyword(s):  
Blood Flow ◽  
Female Rats ◽  
Male Rats ◽  
Resistance Arteries ◽  
Cross Sectional ◽  
Male And Female ◽  
Male And Female Rats ◽  
Arterial Contractility

In resistance arteries, a chronic increase in blood flow induces hypertrophic outward remodeling. This flow-mediated remodeling (FMR) is absent in male rats aged 10 mo and more. As FMR depends on estrogens in 3-mo-old female rats, we hypothesized that it might be preserved in 12-mo-old female rats. Blood flow was increased in vivo in mesenteric resistance arteries after ligation of the side arteries in 3- and 12-mo-old male and female rats. After 2 wk, high-flow (HF) and normal-flow (NF) arteries were isolated for in vitro analysis. Arterial diameter and cross-sectional area increased in HF arteries compared with NF arteries in 3-mo-old male and female rats. In 12-mo-old rats, diameter increased only in female rats. Endothelial nitric oxide synthase expression and endothelium-mediated relaxation were higher in HF arteries than in NF arteries in all groups. ERK1/2 phosphorylation, NADPH oxidase subunit expression levels, and arterial contractility to KCl and to phenylephrine were greater in HF vessels than in NF vessels in 12-mo-old male rats only. Ovariectomy in 12-mo-old female rats induced a similar pattern with an increased contractility without diameter increase in HF arteries. Treatment of 12-mo-old male rats and ovariectomized female rats with hydralazine, the antioxidant tempol, or the angiotensin II type 1 receptor blocker candesartan restored HF remodeling and normalized arterial contractility in HF vessels. Thus, we found that FMR of resistance arteries remains efficient in 12-mo-old female rats compared with age-matched male rats. A balance between estrogens and vascular contractility might preserve FMR in mature female rats.

scholarly journals Assessment of the Central Effects of Natural UraniumviaBehavioural Performances and the Cerebrospinal Fluid Metabolome

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
P. Lestaevel ◽  
S. Grison ◽  
G. Favé ◽  
C. Elie ◽  
B. Dhieux ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Drinking Water ◽  
Locomotor Activity ◽  
Brain Function ◽  
Spatial Working Memory ◽  
Natural Uranium ◽  
Female Rats ◽  
Male Rats ◽  
The Central Nervous System ◽  
And Control

Natural uranium (NU), a component of the earth’s crust, is not only a heavy metal but also an alpha particle emitter, with chemical and radiological toxicity. Populations may therefore be chronically exposed to NU through drinking water and food. Since the central nervous system is known to be sensitive to pollutants during its development, we assessed the effects on the behaviour and the cerebrospinal fluid (CSF) metabolome of rats exposed for 9 months from birth to NUvialactation and drinking water (1.5, 10, or 40 mg·L−1for male rats and 40 mg·L−1for female rats). Medium-term memory decreased in comparison to controls in male rats exposed to 1.5, 10, or 40 mg·L−1NU. In male rats, spatial working memory and anxiety- and depressive-like behaviour were only altered by exposure to 40 mg·L−1NU and any significant effect was observed on locomotor activity. In female rats exposed to NU, only locomotor activity was significantly increased in comparison with controls. LC-MS metabolomics of CSF discriminated the fingerprints of the male and/or female NU-exposed and control groups. This study suggests that exposure to environmental doses of NU from development to adulthood can have an impact on rat brain function.

scholarly journals Changes in RFamide-Related Peptide-1 (RFRP-1)-Immunoreactivity During Postnatal Development and the Estrous Cycle

Endocrinology ◽  
2014 ◽  
Vol 155 (11) ◽  
pp. 4402-4410 ◽  
Author(s):  
Sara R. Jørgensen ◽  
Mille D. Andersen ◽  
Agnete Overgaard ◽  
Jens D. Mikkelsen
Keyword(s):  
Postnatal Development ◽  
Estrous Cycle ◽  
Third Ventricle ◽  
Female Rats ◽  
Male Rats ◽  
Relative Distribution ◽  
Gonadotropin Secretion ◽  
Related Peptide

Abstract GnRH is a key player in the hypothalamic control of gonadotropin secretion from the anterior pituitary gland. It has been shown that the mammalian counterpart of the avian gonadotropin inhibitory hormone named RFamide-related peptide (RFRP) is expressed in hypothalamic neurons that innervate and inhibit GnRH neurons. The RFRP precursor is processed into 2 mature peptides, RFRP-1 and RFRP-3. These are characterized by a conserved C-terminal motif RF-NH2 but display highly different N termini. Even though the 2 peptides are equally potent in vitro, little is known about their relative distribution and their distinct roles in vivo. In this study, we raised an antiserum selective for RFRP-1 and defined the distribution of RFRP-1-immunoreactive (ir) neurons in the rat brain. Next, we analyzed the level of RFRP-1-ir during postnatal development in males and females and investigated changes in RFRP-1-ir during the estrous cycle. RFRP-1-ir neurons were distributed along the third ventricle from the caudal part of the medial anterior hypothalamus throughout the medial tuberal hypothalamus and were localized in, but mostly in between, the dorsomedial hypothalamic, ventromedial hypothalamic, and arcuate nuclei. The number of RFRP-1-ir neurons and the density of cellular immunoreactivity were unchanged from juvenile to adulthood in male rats during the postnatal development. However, both parameters were significantly increased in female rats from peripuberty to adulthood, demonstrating prominent gender difference in the developmental control of RFRP-1 expression. The percentage of c-Fos-positive RFRP-1-ir neurons was significantly higher in diestrus as compared with proestrus and estrus. In conclusion, we found that adult females, as compared with males, have significantly more RFRP-1-ir per cell, and these cells are regulated during the estrous cycle.

scholarly journals Early life stress induces renal dysfunction in adult male rats but not female rats

2013 ◽  
Vol 304 (2) ◽  
pp. R121-R129 ◽  
Author(s):  
Analia S. Loria ◽  
Tatsuo Yamamoto ◽  
David M. Pollock ◽  
Jennifer S. Pollock
Keyword(s):  
Blood Pressure ◽  
Adult Male ◽  
Early Life ◽  
Female Rats ◽  
Male Rats ◽  
Plasma Testosterone ◽  
Ang Ii ◽  
Control Female ◽  
Induced Hypertension ◽  
And Control

Maternal separation (MatSep) is a model of behavioral stress during early life. We reported that MatSep exacerbates ANG II-induced hypertension in adult male rats. The aims of this study were to determine whether exposure to MatSep in female rats sensitizes blood pressure to ANG II infusion similar to male MatSep rats and to elucidate renal mechanisms involved in the response in MatSep rats. Wistar Kyoto (WKY) pups were exposed to MatSep 3 h/day from days 2 to 14, while control rats remained with their mothers. ANG II-induced mean arterial pressure (MAP; telemetry) was enhanced in female MatSep rats compared with control female rats but delayed compared with male MatSep rats. Creatinine clearance (Ccr) was reduced in male MatSep rats compared with control rats at baseline and after ANG II infusion. ANG II infusion significantly increased T cells in the renal cortex and greater histological damage in the interstitial arteries of male MatSep rats compared with control male rats. Plasma testosterone was greater and estradiol was lower in male MatSep rats compared with control rats with ANG II infusion. ANG II infusion failed to increase blood pressure in orchidectomized male MatSep and control rats. Female MatSep and control rats had similar Ccr, histological renal analysis, and sex hormones at baseline and after ANG II infusion. These data indicate that during ANG II-induced hypertension, MatSep sensitizes the renal phenotype in male but not female rats.

Body Adiposity and Endocrine Profile of Female Wistar Rats of Distinct Ages that were Early Weaned

2019 ◽  
Vol 52 (01) ◽  
pp. 58-66 ◽  
Author(s):  
Carla Bruna Pietrobon ◽  
Iala Milene Bertasso ◽  
Beatrix S. Silva ◽  
Nayara Peixoto-Silva ◽  
Elaine Oliveira ◽  
...  
Keyword(s):  
Vitamin D ◽  
Body Fat ◽  
Female Rats ◽  
Male Rats ◽  
Fat Percentage ◽  
Fat Depots ◽  
Lower Body Weight ◽  
Female Wistar Rats ◽  
Endocrine Profile ◽  
And Control

AbstractEarly weaning (EW) is a risk factor for metabolic syndrome. Male rats that were precociously weaned present neonatal malnutrition and, in adulthood, developed overweight, accumulation of body fat, dyslipidemia, changes in glycemic homeostasis, hyperleptinemia, and increase of vitamin D. As metabolic profile of early-weaned females is not known, we investigated the endocrine-metabolic parameters in adolescence and adult female rats of 2 different EW models. Wistar lactating rats and pups from both sexes were separated into 3 groups: non-pharmacological EW (NPEW), dams were involved with a bandage interrupting suckling in the last 3 days of lactation; pharmacological EW (PEW), dams were bromocriptine-treated (0.5 mg/twice a day via intraperitoneal injection) for 3 days before weaning; and control, dams whose pups ate milk throughout lactation. At 21 days-old, NPEW and PEW females had lower body weight. At 180 days-old, NPEW and PEW females showed higher feed efficiency, weight gain, body fat percentage, and greater accumulation of gonadal and retroperitoneal fat depots associated with adipocyte hypertrophy. NPEW females also showed hyperphagia. Only NPEW females presented hyperleptinemia. Plasma thyroid hormones and vitamin D were unchanged among EW females. Regarding sex hormones, at 45 days-old, no change was found in EW females, while at 180 days-old, PEW females had hypoestrogenemia. EW increases the risk for obesity in female rats in adulthood, as already demonstrated for males, although through distinct mechanisms involving some hormones.

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