Protective effects of estrogen on gender-specific development of diet-induced hypertension

2001 ◽  
Vol 91 (5) ◽  
pp. 2005-2009 ◽  
Author(s):  
Christian K. Roberts ◽  
Nosratola D. Vaziri ◽  
R. James Barnard
Keyword(s):  
Body Weight ◽  
Female Rats ◽  
Male Rats ◽  
Gonadal Hormone ◽  
Normal Female ◽  
Humoral Factors ◽  
Diet Modification ◽  
Ovx Rats ◽  
Hormone Status ◽  
Induced Hypertension

Dietary and humoral factors are thought to be involved in the development of hypertension. This study investigated the interaction between diet and gonadal hormone status in the development and reversibility of hypertension. Normal male and female and ovariectomized (OVX) female Fischer rats were placed on either a high-fat (primarily saturated), refined carbohydrate (sucrose) (HFS) or a low-fat, complex carbohydrate (LFCC) diet at 2 mo of age, and body weight and systolic blood pressure (BP) were measured. Male and OVX female rats were initially on the diets for 7 mo, whereas normal female rats were on the diets for 2 yr. After this initial phase, a group of rats from each of the normal HFS groups were converted to the LFCC diet for a period of 1 mo (males) and 2 mo (females). The OVX females were subcutaneously implanted with a 0.5-mg estradiol (E2) pellet for 1 mo. A significant rise in arterial BP occurred within 12 mo in female and only 2 mo in male rats on the HFS diet, exceeding 140 mmHg after 24 and 7 mo, respectively. Conversion from the HFS to the LFCC diet led to a normalization of BP in both female and male rats. HFS diet-induced hypertension was accelerated by OVX in female rats, approaching the pattern seen in male rats. The effect of OVX was completely reversed by E2replacement. BP did not significantly change in any of the LFCC groups at any time point, and E2 replacement had no effect on BP in the OVX LFCC group. All HFS groups had significantly greater body weight, with differences occurring sooner in the male and OVX rats compared with the female rats. Diet modification resulted in a partial but significant reduction of body weight, but E2replacement did not. These results demonstrate that long-term consumption of HFS diet induces hypertension in both genders and is reversible by diet modification. Hypertension is significantly delayed in females with functional ovaries. This protection is lost by OVX and restored by estrogen replacement. Thus hormone status contributes to the delayed onset of diet-induced hypertension in females compared with males.

The anorectic effect of fenfluramine is influenced by sex and stage of the estrous cycle in rats

2005 ◽  
Vol 288 (6) ◽  
pp. R1486-R1491 ◽  
Author(s):  
Lisa A. Eckel ◽  
Heidi M. Rivera ◽  
Deann P. D. Atchley
Keyword(s):  
Food Intake ◽  
Estrous Cycle ◽  
Female Rats ◽  
Male Rats ◽  
Gonadal Hormone ◽  
Estrous Female ◽  
Male And Female Rats ◽  
Daily Food ◽  
Hormone Status ◽  
Anorectic Effect

The controls of food intake differ in male and female rats. Daily food intake is typically greater in male rats, relative to female rats, and a decrease in food intake, coincident with the estrous stage of the ovarian reproductive cycle, is well documented in female rats. This estrous-related decrease in food intake has been attributed to a transient increase in the female rat's sensitivity to satiety signals generated during feeding bouts. Here, we investigated whether sex or stage of the estrous cycle modulate the satiety signal generated by fenfluramine, a potent serotonin (5-HT) releasing agent. To examine this hypothesis, food intake was monitored in male, diestrous female, and estrous female rats after intraperitoneal injections of 0, 0.25, and 1.0 mg/kg d-fenfluramine. The lower dose of fenfluramine decreased food intake only in diestrous and estrous females, suggesting that the minimally effective anorectic dose of fenfluramine is lower in female rats, relative to male rats. Although the larger dose of fenfluramine decreased food intake in both sexes, the duration of anorexia was greater in diestrous and estrous female rats, relative to male rats. Moreover, the magnitude of the anorectic effect of the larger dose of fenfluramine was greatest in estrous rats, intermediate in diestrous rats, and least in male rats. Thus our findings indicate that the anorectic effect of fenfluramine is modulated by gonadal hormone status.

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)

Dexrazoxane does not protect against doxorubicin-induced damage in young rats

2003 ◽  
Vol 285 (2) ◽  
pp. H499-H506 ◽  
Author(s):  
Stéphanie Héon ◽  
Martin Bernier ◽  
Nicolas Servant ◽  
Stevan Dostanic ◽  
Chunlei Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Weight Gain ◽  
Heme Oxygenase ◽  
Caspase 3 ◽  
Exercise Program ◽  
Female Rats ◽  
Male Rats ◽  
Heme Oxygenase 1 ◽  
Cardiac Damage

Doxorubicin (DOX), an anticancer drug, causes a dose-dependent cardiotoxicity. Some evidence suggests that female children have an increased risk for DOX-mediated cardiac damage. To determine whether the iron chelator dexrazoxane (DXR) could reduce DOX-induced cardiotoxicity in the young, we injected day 10 neonate female and male rat pups with a single dose of saline or DOX, DXR, or DXR + DOX (20:1). We followed body weight gain with growth, measured cardiac hypertrophy after a 2-wk swim exercise program, markers of apoptosis (Bcl-2, BAX, BNIP1, caspase 3 activation), oxidative stress (heme oxygenase 1, protein carbonyl levels), the chaperone protein clusterin, and the transcriptional activator early growth response gene-1 (Egr-1) in hearts of nonexercised and exercised rats on neonate day 38. All DOX-alone and DXR + DOX-treated rats showed decreased weight gain, with female rats affected earlier than male rats. DXR-alone, DOX-alone, and DXR + DOX-treated rats had an increased heart weight-to-body weight (heart wt/body wt) ratio after the exercise program with female rats showing the largest increase in heart wt/body wt. Drug-treated females also showed increased cardiac apoptosis, as measured by the increased expression of the proapoptotic proteins BAX and BNIP1 and the appearance of caspase 3 activation products, and oxidative stress, as measured by increased heme oxygenase 1 expression, and reduced Egr-1 and clusterin expression when compared with the similarly treated male rats. We conclude that DXR preinjection did not reduce DOX-induced noncardiac and cardiac damage and that young female rats were more susceptible to DXR and DOX toxicities than age-matched male rats.

scholarly journals Reproductive toxicity of triazole fungicides cyproconazole and epoxiconazole when exposed to male and female wistar rats during gametogenesis

2021 ◽  
Vol 54 (1) ◽  
pp. 52-61
Author(s):  
NR Shepelskaya ◽  
YaV Kolyanchuk
Keyword(s):  
Body Weight ◽  
Reproductive Toxicity ◽  
Reproductive Function ◽  
Female Rats ◽  
Male Rats ◽  
Corpora Lutea ◽  
Disruptive Effect ◽  
Male And Female ◽  
Two Samples ◽  
Adverse Effect Level

Aim. Studying the effect of generic pesticides cyproconazole (98 %) and two samples of epoxiconazole (epoxiconazole 1 — 95,75 % and epoxiconazole 2 — 98,7 %) on the reproductive system of male and female Wistar Han rats at the level of the organism when exposed during gametogenesis, identification and characterization of their hazard, as well as assessment of the risk of reproductive toxicity of these compounds. Materials and Methods. The test samples were administered daily (5 days a week) by oral gavage at doses of 0.2 and 2.0 mg/kg for cyproconazole and 0.5 and 2.0 mg/kg for epoxiconazoles during 11 weeks for males, and 10 weeks for females. Also, there were kept intact males and females, intended for crossover mating with experimental animals. After the end of the exposure, functional indicators of the state of the gonads and the ability of animals to reproduce offspring were studied. The duration and the frequency of each stage of the estrous cycle in female rats and the number of motile sperm, the total amount of sperm and the number of abnormal forms of germ cells of the male rats were studied. The reproductive function state in females was evaluated on day 20th of pregnancy. Thereby the number of corpora lutea in the ovaries, number of alive, dead and resorbed foetuses and embryos, the foetus weight, total weight of litters were registered. The studies were carried out in accordance with the recommendations of the Bioethics Commission and the Centre’s standard operating procedures, developed in accordance with the recommendations and requirements of Good Laboratory Practice (GLP). Conclusions. Test substances at a maximum dose of 2.0 mg/kg of body weight have reproductive toxicity and endocrine-disruptive effect, exerting a significant antiandrogenic effect on males and antiestrogenic effect on female rats. No-observed-adverse-effect-level (NOАEL) for gonadal and reproductive toxicity for male and female Wistar Han rats were established. They are 0.2 mg/kg body weight for cyproconazole and 0.5 mg/kg body weight for epoxiconazole. Key Words: azole fungicides, cyproconazole, epoxiconazole, reproductive toxicity, antiandrogenic and antiestrogenic effects, Wistar Han rats.

Acute and sub-chronic toxicity of the aqueous extract of Ficus vogelii (Miq.) Miq. stem bark in rats

2021 ◽  
Vol 10 (2) ◽  
pp. 89-97
Author(s):  
EL Lappa ◽  
◽  
C Bogning Zangueu ◽  
EL Nguemfo ◽  
JJ Kojom Wanche ◽  
...  
Keyword(s):  
Body Weight ◽  
Aqueous Extract ◽  
Chronic Toxicity ◽  
Hematological Parameters ◽  
Lethal Dose ◽  
Relative Weight ◽  
Stem Bark ◽  
The Body ◽  
Female Rats ◽  
Male Rats

Ficus vogelii is a medicinal plant mainly found in tropical Africa and reported to treat inflammatory complaints. This study aims to evaluate the acute and sub-chronic toxicity of the aqueous extract of Ficus vogelii stem bark in wistar rats. For acute study, aqueous extract at a single dose of 5000 mg/kg body weight was administered to female rats and observed for 14 days. In the sub-chronic study, the extract was administered daily to both sex rats at the doses of 100, 200, 400, and 600 mg/kg body weight for 28 consecutive days. Body weight was measured weekly, while hematological, biochemical, and histopathological parameters were analyzed after euthanize. Aqueous extract of Ficus vogelii at all tested doses didn’t produced any mortality or significant change on the body weight and relative weight of rats on acute and sub-chronic studies. The lethal dose 50 was estimated greater than 5000 mg/kg (DL50˃5000 mg/kg). Hematological parameters were recorded non-significant in all treated rats. Aqueous extract at 600 mg/kg significantly changed transaminases and alkaline phosphatase activities, these changes were reversible in satellites. The concentrations of bilirubin was increased at 200 and 600 mg/kg in male rats, at 100, 400 mg/kg in female rats. The levels of lipids markers didn’t changed, except the significant decrease of LDL-cholesterol. Histological examination didn’t showed any change in the architecture of the liver and kidney of rats treated compared to control. Thus aqueous extract of Ficus vogelii stem bark didn’t produced adverse effects in rats after oral acute and sub-chronic treatment.

Hepatic alpha 2 mu-globulin: a potential metabolic role in the rat proximal tubule

1996 ◽  
Vol 271 (3) ◽  
pp. F527-F538 ◽  
Author(s):  
S. C. Borkan ◽  
Y. H. Wang ◽  
K. T. Lam ◽  
P. Brecher ◽  
J. H. Schwartz
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Proximal Tubule ◽  
Glucose Oxidation ◽  
Renal Cortex ◽  
Female Rats ◽  
Male Rats ◽  
Normal Female ◽  
Fatty Acid Binding ◽  
Oxidation Rates

In the present study, we provide immunohistochemical and immunologic evidence to localize an abundant, 15.5-kDa protein to the soluble protein fraction of the proximal tubule. This 15.5-kDa protein binds fatty acids in vitro and has identity with amino acids 10-117 of alpha 2 mu-globulin (A2 fragment), a 19-kDa protein synthesized predominantly in the male liver. With reverse transcription-polymerase chain reaction, mRNA for A2 was detected in male liver but not in the male kidney. De novo accumulation of the 15.5-kDa protein was observed in the renal cortex of female rats given intravenous injections of purified 19-kDa protein (A2), suggesting intrarenal processing of the larger protein. The potential role of this protein in the proximal tubule, a site that utilizes fatty acids as an important metabolic substrate, was determined in isolated proximal tubule segments. Fatty acid and glucose oxidation rates were measured in three experimental models in which the 15.5-kDa protein was virtually absent: 1) uninephrectomized male rats treated with deoxycorticosterone acetate and salt, 2) male rats subjected to bilateral adrenalectomy, and 3) normal female rats. In the absence of the 15.5-kDa protein, fatty acid oxidation rates decreased by 30-55%, whereas glucose oxidation significantly increased in all three models. In female renal cortex, depletion of the 15.5-kDa protein was associated with a rise in heart fatty acid binding protein, an alternative intracellular transporter of fatty acids. These data support the hypothesis that a proteolytic cleavage product of hepatic alpha 2 mu-globulin may facilitate the oxidation of oleate, a hydrophobic ligand, in the proximal tubule.

Metabolic Rate of Female Rats as a Function of Age and Body Size

1956 ◽  
Vol 186 (1) ◽  
pp. 9-12 ◽  
Author(s):  
Max Kleiber ◽  
Arthur H. Smith ◽  
Theodore N. Chernikoff
Keyword(s):  
Body Weight ◽  
Body Size ◽  
Metabolic Rate ◽  
Age Groups ◽  
Female Rats ◽  
Standard Errors ◽  
Normal Female ◽  
Metabolic Rates ◽  
The Mean ◽  
Specific Unit

On the basis of 926 respiration trials, metabolic rates of normal female rats are presented as means of 42 different age groups from birth to 1000 days of age. The means with their standard errors are given for the metabolic rates per rat, per kilogram weight, per unit of the 2/3 power of body weight (surface), and per unit of the 3/4 power of body weight (inter specific unit of metabolic body size). A minimum of 72.6 Cal/kg.3/4 occurs between the ages of 200 and 300 days. An equation with two exponentials predicts the metabolic rate of rats from 77–1000 days of age with a standard deviation between prediction and observation of 2.2% of the mean.

Toxicity Assessment of 4-Amino-2-Nitrotoluene

2013 ◽  
Vol 32 (2) ◽  
pp. 113-122 ◽  
Author(s):  
John T. Houpt ◽  
Glenn J. Leach ◽  
Larry R. Williams ◽  
Mark S. Johnson ◽  
Gunda Reddy
Keyword(s):  
Adverse Effect ◽  
Body Weight ◽  
Weight Gain ◽  
Body Weight Gain ◽  
Toxicity Study ◽  
Female Rats ◽  
Male Rats ◽  
Toxicity Data ◽  
Adverse Effect Level ◽  
Effect Level

4-Amino-2-nitrotoluene (4A2NT; CAS 119-32-4) is a degradation product of 2,4-dinitrotoluene. The toxicity data on 4A2NT are limited. Therefore, we collected toxicity data from rats to assess environmental and human health effects from exposures. The approximate lethal dose for both sexes was 5000 mg/kg. A 14-day toxicity study in rats was conducted with 4A2NT in the feed at concentrations of 0, 125, 250, 500, 1000, and 2000 ppm. Based on a 14-day oral dose range toxicity study with 4A2NT in the feed, 2000 ppm was selected as highest concentration for a subsequent 90-day study. An oral 90-day subchronic toxicity study in rats was conducted with concentrations of 0, 500, 1000, or 2000 ppm of 4A2NT in the feed. The calculated consumed doses of 4A2NT in the feed were 0, 27, 52, or 115 mg/kg/d for males and 0, 32, 65, or 138 mg/kg/d for females. A no-observed adverse effect level could not be determined. The lowest observed adverse effect level was 27 mg/kg/d for males and 32 mg/kg/d for female rats based upon decreased body weight gain. The decreased body weight gain in male rats was the most sensitive adverse event observed in this study and was used to derive a benchmark dose (BMD). A BMD of 23.1 mg/kg/d and BMD with 10% effect level of 15.5 mg/kg/d were calculated for male rats, which were used to derive an oral reference dose (RfD). The human RfD of 1.26 μg/kg/d was derived using current United States Environmental Protection Agency guidelines.

FACTORS INFLUENCING THE EXCRETION OF A FAT-MOBILIZING SUBSTANCE IN THE URINE OF RATS

1966 ◽  
Vol 44 (1) ◽  
pp. 95-101 ◽  
Author(s):  
J. R. Beaton ◽  
A. J. Szlavko ◽  
J. A. F. Stevenson
Keyword(s):  
Body Weight ◽  
Sex Difference ◽  
Specific Activity ◽  
Young Male ◽  
Total Activity ◽  
Female Rats ◽  
Male Rats ◽  
Diabetic Rat ◽  
Adult Rats ◽  
Factors Influencing

The effect of various factors on excretion of a lipid-mobilizing activity in FMS IA (anorexigenic) and in FMS IB (fat-mobilizing) by the fasting rat has been investigated. During fasting, the greatest excretion of such activity in FMS IA and FMS IB occurred in the first 24 hours and diminished thereafter up to 72 hours; and the specific activity of FMS IB was greatest in the first 24 hours whereas that of FMS IA was constant throughout. The hypothalamicobese rat excretes FMS IA and FMS IB in greater than normal amounts. The alloxan-diabetic rat excretes less total activity of FMS IA and IB than do control animals. Young male rats excrete greater amounts of FMS IB, but not of FMS IA, than do adult rats, the greatest excretion per 100 g body weight being observed at approximately 37 days of age. At 27 days of age (prepuberty), male rats excreted a greater total activity of FMS IB but not of FMS IA than did female rats. At 90 days of age (post-puberty), there was no apparent sex difference in the amount of total activity of FMS IB excreted per rat, but when expressed per 100 g body weight, females excreted more FMS IB than did males.

EFFECTS OF TESTOSTERONE MEDIATED OR MODULATED BY PITUITARY FACTORS

1975 ◽  
Vol 67 (1) ◽  
pp. 71-79 ◽  
Author(s):  
P. DE MOOR ◽  
M. ADAM-HEYLEN ◽  
H. VAN BAELEN ◽  
G. VERHOEVEN
Keyword(s):  
Body Weight ◽  
Testosterone Propionate ◽  
Total Body Weight ◽  
Seminal Vesicles ◽  
Female Rats ◽  
Male Rats ◽  
Intact Male ◽  
Adult Rats ◽  
Organ Weights ◽  
Total Body

SUMMARY Adult rats of both sexes were either gonadectomized or hypophysectomized and gonadectomized. Three to eight weeks later they were treated for 14 consecutive days with oil or with 75 or 200 μg testosterone propionate (TP) per 100 g body weight. The animals were killed and for each sex the gonadectomized animals were compared with the hypophysectomized-gonadectomized animals as far as their NADPH- and NADH-dependent 3α-hydroxysteroid dehydrogenases (3α-HSD) in renal microsomes, transcortin levels in serum and five organ weights relative to total body weight were concerned. For two of the latter, i.e. the relative kidney and prostatic weights, no significant differences were found. Transcortin levels, relative adrenal weights and renal NADPH-dependent 3α-HSD activities were higher in oil-treated gonadectomized animals than in oil-treated hypophysectomized-gonadectomized animals. The opposite was found for the relative weights of uterus and seminal vesicles and renal NADH-dependent 3α-HSD activities. These differences between gonadectomized and hypophysectomized-gonadectomized animals disappeared after TP treatment as far as transcortin levels were concerned but remained for the five other parameters. After gonadectomy sexual differences subsisted for all parameters studied. But whereas intact male rats had higher NADH-dependent 3α-HSD activities than female rats the opposite was found after gonadectomy. After gonadectomy plus hypophysectomy the between sex differences disappeared as far as transcortin levels were concerned but remained in the other parameters studied.

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