Effect of aspirin on adrenal weight in female rats.

Daily ingestion of Purina laboratory chow supplemented with 1% powdered aspirin for 25 days caused a marked depression in adrenal weight as well as decreased body weight and ovarian and uterine weight. The action of aspirin on adrenal weight did not appear to be mediated through pituitary-ovarian activity as measured by organ weight indices of sham and hemiovariectomized female rats.     

The oral administration of Polysorbate 80 to the immature female rat does not increase uterine weight

Some xenobiotics display estrogenic activity in in vitro and/or in vivo systems. Previous studies by Gajdova et al. have shown that polysorbate 80 (also known as Tween 80) administered by intraperitoneal injection to neonatal female rats on days 4–7 after birth produced estrogenic effects including earlier vaginal opening, prolongation of the estrus cycle and persistent vaginal estrus [1]. Some of these effects were evident many weeks after cessation of administration of polysorbate 80. The present study has evaluated the estrogenic properties of polysorbate 80 following oral administration, a route of exposure which is more relevant for the consideration of human health hazard. The effects of polysorbate 80 at oral gavage doses of up to 5 g/kg/day for 3 consecutive days on uterine growth of immature female rats, a commonly used in vivo mammalian assay for estrogenic activity, have been determined. Estradiol benzoate administered subcutaneously was used as a positive control and significantly increased uterine weight in this age and strain of female rat (21–23 days, Alpk:APfSD Wistar derived) by up to 4.5-fold above vehicle control values. Polysorbate 80 administered orally to rats had no effect on uterine weight. Thus, intrinsic estrogenic effects of polysorbate 80 reported following its intraperitoneal injection to neonatal 4-day-old female rats are not manifest when it is administered by oral gavage to immature 20- to 22-day-old female rats. This latter route of exposure is of more relevance to human exposure scenarios and these data are, therefore, important in assessing hazard/risk of polysorbate 80 to man.     

Effect of 2,5-dimethylpyrazine on uterine contraction in late stage of pregnant female rats

Effect of 2,5-dimethylpyrazine (2,5-DMP) on oxytocic agent-induced late pregnant uterine contraction in female rats was studied. Oxytocic agents induced-hypercontraction in the late phase of pregnant uterine movements were inhibited by administration of 2,5-DMP. The inhibition of uterine contraction was obtained more strengthening by presence of a low dose of ritodrine hydrochloride than 2,5-DMP alone. These results suggests that 2,5-DMP has an inhibitory action on uterine hypercontraction induced by oxytocic agent through the beta2-adrenoceptor in the pregnant uterus and supports the applicability of relaxing drugs for oxytocic agent-induced accidents.     

Effect of gonadotropin-releasing hormone antagonist on ovarian and uterine weights in immature female rats

The immature rat uterotrophic assay has been proposed as a screening test method for detecting estrogenic and antiestrogenic chemicals. Although the immature rat uterotrophic assay is advantageous because the test animals are not traumatized by the ovariectomizing process, the effect of endogenous estrogen on ovarian and uterine weight in the immature animals that are used in immature rat uterotrophic assay has not received much attention. In this study, 19-day-old rats were treated with antide, a gonadotropin-releasing hormone antagonist, antide, to block gonadal production of endogenous estrogen. Uterine and ovarian weights of the antide-treated animals were markedly lower than those of control animals. This finding suggests that endogenous gonadal estrogen may already be acting on the uterus and ovaries in immature rats. Blocking endogenous estrogen with a gonadotropin-releasing hormone antagonist may enhance the sensitivity of the immature rat uterotrophic assay; however, the possibility that this protocol may interfere with the ability of the immature rat uterotrophic assay to detect centrally-mediated effects can not be discounted.     

Effects of the classical antipsychotic haloperidol and atypical antipsychotic risperidone on weight gain, the oestrous cycle and uterine weight in female rats.

Antipsychotic drug-induced side effects of weight gain and sexual dysfunction have clinical significance adversely affecting both compliance and morbidity. This study evaluated the effects of haloperidol and the atypical antipsychotic risperidone (0.1-1.0 mg/kg) on weight gain, food and water intake, the oestrous cycle and uterine weight in female hooded Lister rats. Haloperidol and risperidone treated rats displayed marked weight gain, although only risperidone induced significant increases in food consumption over the 21-day period. Neither haloperidol nor risperidone influenced water consumption. Marked disruption of the oestrous cycle was observed in risperidone- and haloperidol-treated animals (0.5 and 1.0 mg/kg), which was supported by significantly reduced uterine weights. The findings presented here suggest that the weight gain and sexual dysfunction induced by antipsychotics may be modelled in rodents. This model may offer insight into the mechanisms involved in mediation of such side effects.     

Copper nanoparticle‐induced uterine injury in female rats

Copper nanoparticles (Cu‐NPs) have been used increasingly in various products and applications. Although recent studies have reported that exposure to Cu‐NPs leads to organ accumulation and obvious toxicity, it remains unclear whether Cu‐NPs can be translocated to and cause damage in the uterus. In this study, we investigated the potential for uterine injury and gene expression patterns in female rats exposed to 3.12, 6.25, or 12.5 mg/kg/d Cu‐NPs via intraperitoneal injection for 14 consecutive days. The results indicated that exposure to Cu‐NPs led to significant decreases in the relative uterine weight coefficients and increases in inflammatory cell infiltration, mitochondrial swelling and vacuolization, shortened and reduced endometrial epithelial cell microvilli, and apoptosis. Furthermore, exposure to Cu‐NPs increased malondialdehyde (MDA) accumulation and decreased superoxide dismutase (SOD) levels. Signal transduction mechanism studies indicated that exposure to Cu‐NPs activated caspases 3, 8, and 9 and BH3 interacting domain death agonist (tBid), reduced B cell leukemia/lymphoma 2 (Bcl‐2) expression, and increased the expression of apoptotic peptidase activating factor 1 (Apaf‐1), BCL2‐associated X, apoptosis regulator (Bax), and cytochrome c. A microarray analysis revealed significant alterations in the expression of 963 genes; of these, 622 were upregulated and 341 were downregulated. The results of further evaluations of some altered genes, including matrix metallopeptidase 12 (Mmp12), using quantitative RT‐PCR agreed with the microarray findings. These results provide strong evidence that Cu‐NPs can trigger both intrinsic and extrinsic apoptotic pathways to mediate uterine injury, resulting in oxidative stress‐related changes in gene expression.     

Effect of histamine on uterine vasculature in rats.

The effects of histamine infusions on the rat uterine vasculature have been studied using the radioactive microsphere technique. Histamine produced a marked uterine vasodilatation which could be partly mimicked by infusion of either the H1-receptor agonist, 2-(2-aminoethyl)pyridine, or the H2-receptor agonist, 4-methyl-histamine. Histamine-induced uterine vasodilatation could only be reduced significantly by administration of a combination of the H1- and H2-receptor antagonists mepyramine and metiamide but not by either antagonist given alone. It was concluded that histamine-induced vasodilatation in the rat uterus is mediated by both H1- and H2-receptors.     

Effects of nicotine on body weight and food consumption in female rats

Women often report that they smoke cigarettes to avoid weight gains and that they relapse after abstaining from tobacco because of weight gains. Men also report these concerns but to a lesser extent. This gender difference may reflect sociological and cultural pressures about physical appearance, or it may reflect sex differences in the effects of nicotine. The present research was designed to examine the effects of nicotine administration and cessation of nicotine on body weight, food consumption, and water consumption. Alzet miniosmotic pumps were implanted SC to administer saline or three different concentrations of nicotine to female Sprague-Dawley rats for 17 days. This paradigm has been used in previous studies of nicotine and body weight in male rats. Animals were used as subjects to avoid cultural factors and cognitive concerns about body weight. Nicotine administration decreased normal body weight gains and cessation of nicotine was accompanied by significant increases in body weight compared to controls. In contrast to previous studies of male rats, the nicotine-related changes in body weight were accompanied by changes in bland food and water consumption. These findings indicate that females are more sensitive than males to the effects of nicotine on body weight and feeding during and after drug administration.     

Comparative studies on the increase of uterine weight and related mechanisms of cadmium and p-nonylphenol

The research was designed to compare the effect of cadmium and p-nonylphenol on the increase of uterine weight and to study the related mechanisms. It provided basic evidence for us to understand the possible different mechanisms among different EEDs. In this study, both ovaries of 60 Wistar rats (28 days age) were ectomized, and after 21 days recovery, the rats were randomly assigned into six groups and exposed to cadmium (0.12, 1.20mg/kg), NP (100, 200mg/kg), control (sterile PBS), and positive control (17beta-estradiol) per day for 3 days, respectively, then related indexes were detected. The results showed that the increase of uterine weight induced by cadmium was accompanied by the increase of the thickness of luminal epithelium cell and endometrium but the decrease of nuclear/cytoplasm of luminal epithelium cell and endometrium, while the increase of uterine weight induced by p-nonylphenol was accompanied by the increase of the thickness of luminal epithelium cell, endometrium, and myometrium but the decrease of nuclear/cytoplasm of luminal epithelium cell and endometrium. Cadmium could inhibit the positive expression of PCNA while p-nonylphenol prompted it. Exposure to cadmium and NP both could also stimulate phosphorylation of ERK mitogen-activated protein kinases, implying that this signal pathway had an effect on the increase of the uterine weight induced by cadmium and p-nonylphenol. The results indicate that cadmium may induce the increase of uterine weight, which is accompanied with toxic effect on endometrium, while NP's effect of the increase of uterine weight is due to cell proliferation of endometrium, the mechanisms of which are the same as estrogen, but they may both activate ERK signal pathway.     

Effects of body weight on taste of male and female rats

Single-choice taste (solution and mixed-diet) tests revealed that ad lib fed male rats with increasing body weight showed increased intake on sweet taste as compared to intake of identically aged ad lib fed female rats with static body weight. On meal-time (3 hr) and meal-size (50% diet) restrictions though rats of either sex increased on intake of sweet taste, the increment shown by female was higher and it was correlated with their greater % loss in bw. Hence it appears that the basis for sweet taste preference is the mismatch between actual and target body weight irrespective of sex of animal.     

A parametric analysis of olanzapine-induced weight gain in female rats

RATIONALE: Some novel antipsychotics, including olanzapine, induce weight gain and metabolic abnormalities, which represent the major adverse effects of these drugs. However, the mechanism(s) involved in such effects are unclear. OBJECTIVE: The aim of this study was to develop, in female rats, a parametric model of olanzapine-induced weight gain and metabolic abnormalities and evaluate it against clinical findings. METHODS: Female rats were administered olanzapine b.i.d. at doses of 0, 1, 2 and 4 mg/kg over 20 days, and a wide range of variables were recorded during and after drug administration. RESULTS: Olanzapine increased both 24 h and total food intake. This was associated with rapid onset weight gain and increased adiposity (assessed by visceral fat pad masses). Insulin, but not glucose, concentrations were elevated, with a significant increase in the HOMA-IR index, indicative of insulin resistance. A nonsignificant trend towards higher levels of leptin was observed. Paradoxically, there was a significant increase in adiponectin. All of these variables showed maximal increases at either 1 or 2 mg/kg and attenuated effects at 4 mg/kg. Prolactin levels were also increased by olanzapine. However, for this variable, there was a clear dose-response curve, with the maximal effect at the highest dose (4 mg/kg). CONCLUSIONS: These data suggest that aspects of olanzapine-induced weight gain and metabolic abnormalities can possibly be modelled in female rats. It is suggested that olanzapine-induced hyperphagia acts as an initial stimulus which leads to weight gain, enhanced visceral adiposity and subsequent insulin resistance, although the latter may be ameliorated by compensatory responses in adiponectin levels. Prolactin elevation appears likely not to be involved in the weight gain, adiposity and metabolic changes seen in this model.     

Effect of karphedone on reproduction function in female rats

Karphedone treatment (50 mg/kg over a period of two weeks) increased the ovary weight coefficient and increased the gestation index in female rats, while not affecting the terms of pregnancy and the characteristics of embryo development. At the same time karphedone decreased nicotinic cholinoreceptor mediated CNS activity, but produced no dopaminergic action.     

All-trans retinoic acid protects against arsenic-induced uterine toxicity in female Sprague-Dawley rats

Background and purpose

Arsenic exposure frequently leads to reproductive failures by disrupting the rat uterine histology, hormonal integrity and estrogen signaling components of the rat uterus, possibly by generating reactive oxygen species. All-trans retinoic acid (ATRA) was assessed as a prospective therapeutic agent for reversing reproductive disorders.

Experimental approach

Rats exposed to arsenic for 28 days were allowed to either recover naturally or were treated simultaneously with ATRA for 28 days or treatment continued up to 56 days. Hematoxylin-eosin double staining was used to evaluate changes in the uterine histology. Serum gonadotropins and estradiol were assayed by ELISA. Expression of the estrogen receptor (ERα), an estrogen responsive gene vascular endothelial growth factor (VEGF), and cell cycle regulatory proteins, cyclin D1 and CDK4, was assessed by RT-PCR, immunohistochemistry and western blot analysis.

Key results

ATRA ameliorated sodium arsenite-induced decrease in circulating estradiol and gonadotropin levels in a dose- and time-dependent manner, along with recovery of luminal epithelial cells and endometrial glands. Concomitant up regulation of ERα, VEGF, cyclin D1, CDK4 and Ki-67 was also observed to be more prominent for ATRA-treated rats as compared to the rats that were allowed to recover naturally for 56 days.

Conclusions and implications

Collectively, the results reveal that ATRA reverses arsenic-induced disruption of the circulating levels of gonadotropins and estradiol, and degeneration of luminal epithelial cells and endometrial glands of the rat uterus, indicating resumption of their functional status. Since structural and functional maintenance of the pubertal uterus is under the influence of estradiol, ATRA consequently up regulated the estrogen receptor and resumed cellular proliferation, possibly by an antioxidant therapeutic approach against arsenic toxicity.     

Effect of bromocriptine on uterine contractility in near-term pregnant rats.

Treatment of pregnant albino rats at gestation day 9 with the dopamine agonist, bromocriptine, in a dose of 0.7 mg kg-1 day-1, i.p. for 11 days produced a significant increase in the normal uterine contractions both in vitro and in vivo. The increase in frequency (F), amplitude (A) and area under the curve (AUC) in the in vitro experiment amounted to 35, 80 and 58%, respectively; while the increase in F and A in the in vivo experiment was 36 and 25%, respectively, in comparison with the corresponding control group. Addition of oxytocin (5x10(-12)-4x10(-11) m) to the uterus isolated from rats pretreated with bromocriptine resulted in marked uterotonic effect (24, 35 and 49% increase in F; 25, 35 and 46% increase in A and 42, 62 and 122% increase in AUC of contractions). Also, the in vivo experiment showed that an injection of oxytocin at the time of investigation (0.125-1.0 I.U. kg-1, i.v.) into rats pretreated with bromocriptine caused a marked increase in F (33, 40 and 81%) and A (33, 37 and 75%) of uterine contractions compared to the values of bromocriptine-treated animals. These results indicate that bromocriptine should be used with caution during pregnancy. In addition, this must be considered when using oxytocin during delivery of females pretreated with bromocriptine.     

Effect of 3,6-dimethamidodibenzopyriodonium citrate on Ca~(2 ) in rabbit platelet in vitro

目的：观察Ｉ６５对家兔血小板胞浆游离钙离子（［Ｃａ２＋］ｉ）浓度的影响．方法：用Ｑｕｉｎ２ＡＭ荧光探针在体外测定家兔血小板［Ｃａ２＋］ｉ．结果：ＣａＣｌ２１ｍｍｏｌ·Ｌ－１时，Ｉ６５（１０，２０和３０μｍｏｌ·Ｌ－１）使血小板［Ｃａ２＋］ｉ分别由１４２±２２ｎｍｏｌ·Ｌ－１和１２４±１８ｎｍｏｌ·Ｌ－１减少到１１８±２０，７８±１２，４０±１０ｎｍｏｌ·Ｌ－１和１０８±１５，７７±１４，３７±１４ｎｍｏｌ·Ｌ－１．用依他酸２ｍｍｏｌ·Ｌ－１络合胞外Ｃａ２＋，Ｉ６５胞内贮存Ｃａ２＋释放从５２±１１ｎｍｏｌ·Ｌ－１减少至３４±９，１９±６和１１±５ｎｍｏｌ·Ｌ－１．另外，Ｉ６５也使胞外Ｃａ２＋跨膜内流从９１±１３ｎｍｏｌ·Ｌ－１分别降至８４±１５，５８±１５和２８±１９ｎｍｏｌ·Ｌ－１．结论：Ｉ６５不仅明显抑制家兔血小板胞外Ｃａ２＋跨膜内流而且抑制胞内贮存Ｃａ２＋释放．     

大豆异黄酮对雌性大鼠内分泌功能的影响

目的动物实验观察大豆异黄酮对雌性大鼠内分泌功能的影响。方法12周龄雌性大鼠42只随机分配为三组：低剂量组每日灌胃大豆异黄酮40mg·kg^-1·d^-1,高剂量组每日灌胃大豆异黄酮80mg·kg^-1·d^-1,对照组灌胃0．9％氯化钠注射液。14d后颈静脉取血,采用化学发光法分别测定促卵泡生成素（FSH）、促黄体生成素（LH）、雌二醇（E2）和孕酮（P）四项指标。结果大豆异黄酮低剂量组、高剂量组和对照组三组FSH分别为（0．13±0．02）mIu／ml、（0．12±0．02）mIu／ml、（0．15±0．02）mIu／ml,LH分别为（0．17±0．03）mlu／ml、（O．15±0．04）mIu／ml、（0．18±0．05）mIu／ml,三组相比较差异无统计学意义（P〉0．05）;三组E2分别为（0．09±0．03）nmol／L、（0．03±0．03）nmol／L、（0．12±O．04）nmol／L;P分别为（1．43±0．27）ng／ml、（2．82±0．37）-s／ml、（0．67±0．56）ng／ml。三组相比较大豆异黄酮组的E2活性明显降低（P〈0．01）,尤其高剂量组的降低更为显著。大豆异黄酮组的P水平较对照组明显升高（P〈0．01）,而高剂量组P的升高更为显著。结论大豆异黄酮对大鼠的垂体激素无明显影响,不同剂量的大豆异黄酮可能通过雌激素活性和抗雌激素活性而影响雌性大鼠卵巢激素的分泌调节。     

Characterisation of olanzapine-induced weight gain and effect of aripiprazole vs olanzapine on body weight and prolactin secretion in female rats

Rationale Atypical antipsychotic drug (APD)-induced weight gain causes non-compliance, increasing the risk of relapse and medical complications. Objectives In an animal model, we assessed body weights, food intake, body fat/lean body mass contents and blood serum levels of glucose and lipids in female rats treated with olanzapine (Experiment 1). Also, we investigated the effect of aripiprazole vs olanzapine treatment on weight gain (WG) and plasma prolactin secretion in two strains (Wistar and Sprague–Dawley) and in two housing conditions (singly and group housed; Experiment 2). Methods In Experiment 1, Wistar females received either vehicle or olanzapine (5.0 mg kg⁻¹, p.o.) twice daily for 14 days. In Experiment 2, female rats (Wistar or Sprague–Dawley), housed singly or in groups, received either vehicle, aripiprazole (2.0–8.0 mg kg⁻¹, p.o.), or olanzapine (1.0–10 mg kg⁻¹, p.o.) twice daily for 7 days. Body weights and food intake were assessed daily. Body composition and blood assays were analyzed at the end of the treatment. Results WG induced by chronic olanzapine treatment was characterised by hyperphagia, increased body fat, and serum free fatty acid content and reduced lean tissue and serum glucose content. Subchronic aripiprazole treatment resulted in rapid and robust WG similar to those observed with olanzapine. In spite of similar effects on body weight, aripiprazole and olanzapine stimulated markedly different patterns of prolactin secretion. Body weight changes and prolactin secretion induced by these APDs were significantly modulated by housing and by strain. Conclusion Assessment of body weight in the present model may not have predictive validity, and other measures may be needed to differentiate between WG-inducing and weight-neutral drugs.     

Effects of the atypical antipsychotic olanzapine on reproductive function and weight gain in female rats

Sexual dysfunction is a major, although poorly understood, side-effect of treatment with antipsychotic drugs. We have recently show marked disruption of reproductive function and weight gain in female rats treated subchronically with risperidone and haloperidol. The aim of the present study was to examine further the potential relationship between reproductive dysfunction and weight gain in female rats treated with olanzapine. The effects of olanzapine on weight gain, food and water intake, intra-abdominal fat, the oestrous cycle and uterine weight were assessed in group-housed adult female hooded-Lister rats. Olanzapine (0.5-4.0 mg/kg i.p.) or vehicle was administered once daily for 21 days and body weight, food and water intake measured, with histological examination of vaginal lavage to determine the stage of the oestrous cycle. On day 22, animals were sacrificed and intra-abdominal fat, wet and dry uterine weights measured. Olanzapine induced significant weight gain with concomitant increases in food and water intake and intra-abdominal fat without an effect on the oestrous cycle, wet and dry uterine weights or plasma prolactin levels. These results confirm the ability of olanzapine to induce weight gain in female rats on unrestricted normal diet with a concomitant increase in food and water intake and increased intra-abdominal fat. These effects of olanzapine were produced in the absence of any apparent impairment in reproductive function, in contrast to the substantial disruption of oestrous and uterine atrophy previously shown in rats treated with risperidone and haloperidol.