Effects of 17β-estradiol and antioxidant administration on oxidative stress and insulin resistance in ovariectomized rats

The prevalence of insulin resistance syndrome increases during menopause with the overproduction of reactive oxygen species and impairment of the free radical scavenger function. Therefore, we investigated the effects of 17β-estradiol (E(2)) and vitamin E, as an antioxidant, on lipid peroxidation and antioxidant levels in the brain cortex and liver of ovariectomized rats as well as on insulin resistance in those rats. Forty female Sprague-Dawley rats, 3?months of age and weighing 231.5?± 9.4 g, were divided into 4 groups: sham, ovariectomized (OVX), OVX treated with E(2) (40 μg/kg subcutaneously), and OVX treated with E(2) and vitamin E (100?mg/kg intraperitoneally). The 4 groups received the appropriate treatment every day for 8?weeks. Levels of glutathione, glutathione peroxidase, superoxide dismutase , catalase, and malondialdehyde in the brain cortex and liver of ovariectomized rats were measured. Also, fasting plasma insulin, glucose, and homeostatis model assessment of insulin resistance (HOMA-IR) were determined. Malondialdehyde increased and antioxidants (glutathione, glutathione peroxidase, catalase, superoxide dismutase) decreased in the brain cortex and liver of OVX rats. Also, fasting glucose, insulin, and HOMA-IR increased in OVX rats. E(2) and E(2) plus vitamin E decreased malondialdehyde and increased antioxidants in the brain cortex and liver of OVX rats. Moreover, they decreased fasting glucose, insulin, and HOMA-IR in ovariectomized rats. This study demonstrates that E(2) and E(2) plus vitamin E supplementation to OVX rats may improve insulin resistance, strengthen the antioxidant system, and reduce lipid peroxidation.     

Induction of sexual receptivity in ovariectomized female rats by subcutaneous implants of estradiol-17β

Ovariectomized female rats were implanted with estradiol-17β (E₂)-filled Silastic capsules at various times and the display of sexual receptivity in response to progesterone (P) treatment, 42 hr after the initiation of E₂ treatment, was observed. Exposure to E₂ for 24 hr or less was insufficient to prepare the animals to respond to P treatment. Implantation of E₂-filled capsules for 48 hr, however, brought all animals into sexual receptivity. Anti-estrogen treatment, both at the time of implantation of E₂-filled capsules and 24 hr after implantation, partially inhibited the effect of a 48-hr exposure to E₂ on the display of sexual behavior. Continued presence of e₂ may be necessary for display of sexual receptivity by Ovariectomized rats.     

Ameliorative effect of 20-OH ecdysone on streptozotocin induced oxidative stress and β-cell damage in experimental hyperglycemic rats

The present study was to evaluate the effects of 20-OH ecdysone on hyperglycemia mediated oxidative stress in streptozotocin induced diabetic rats. Diabetes was induced in experimental rats by single intraperitoneal injection of STZ (45 mg/kg b.w.) dissolved in 0.1 mol/L citrate buffer (pH 4.5). Diabetic rats exhibited increased blood glucose with significant decrease in plasma insulin levels. The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and the levels of non-enzymic antioxidants vitamin C, vitamin E and reduced glutathione (GSH) were decreased while increases in the levels of LPO markers were observed in liver and kidney tissues of diabetic rats. Moreover, hepatic markers (aspartate aminotransferase and alanine aminotransferase) and renal markers (urea, creatinine) were significantly increased in diabetic rats as compared to control rats. Upon treatment with 20-OH ecdysone to diabetic rats showed significant ameliorative effects on all the biochemical parameters studied. Biochemical findings were supported by histological studies. These results indicated that 20-OH ecdysone exerts a protective action on pancreatic beta cell function and overcomes oxidative stress through its hypoglycemic potential. The effect produced by the 20-OH ecdysone on various parameters was comparable to that of glibenclamide – an antidiabetic drug.     

Mitochondrial mechanism of cardiomyocyte apoptosis induced by stress

Stress induced the serious disorder of cardiac function and cardiovascular diseases. Apoptosis is the cellular basis in stress induced cardiac injury. In our previous study we found that many stressors resulted in mitochondrial damage. It is certain that mitochondria is important mediator in triggering apoptotic cell death, but the mechanism, by which the stress induced mitochondrial injury leads to cardiomyocyte apoptosis, remains unclear. We designed the present study to investigate the changes of the mitochondria in cardiomyocytes undergoing stress and its role in inducing apoptosis. Here we reported that stress changed the membrane fluidity of mitochondria and induced the lipid peroxidation of mitochondrial membrane in     

Tamarix gallica ameliorates thioacetamide–induced hepatic oxidative stress and hyperproliferative response in Wistar rats

Tamarix gallica, a hepatic stimulant and tonic, was examined for its ability to inhibit thioacetamide (TAA)-induced hepatic oxidative stress, toxicity and early tumor promotion response in male Wistar rats. TAA (6.6 mmol/kg body wt. i.p) enhanced lipid peroxidation, hydrogen peroxide content, glutathione S-transferase and xanthine oxidase with reduction in the activities of hepatic antioxidant enzymes viz., glutathione peroxidase, superoxide dismutase and caused depletion in the level of hepatic glutathione content. A marked increase in liver damage markers was also observed. TAA treatment also enhanced tumor promotion markers, ornithine decarboxylase (ODC) activity and [³H] thymidine incorporation into hepatic DNA. Pretreatment of rats orally with Tamarix gallica extract (25 and 50 mg/kg body weight) prevented TAA-promoted oxidative stress and toxicity. Prophylaxis with Tamarix gallica significantly reduced the susceptibility of the hepatic microsomal membrane for iron-ascorbate induced lipid peroxidation, H₂O₂ content, glutathione S-transferase and xanthine oxidase activities. There was also reversal of the elevated levels of liver marker parameters and tumor promotion markers. Our data suggests that Tamarix gallica is a potent chemopreventive agent and may suppress TAA-mediated hepatic oxidative stress, toxicity, and tumor promotion response in rats.     

Systemic and intra-rhinal-cortical 17-β estradiol administration modulate object-recognition memory in ovariectomized female rats

Previous studies using the novel-object-preference (NOP) test suggest that estrogen (E) replacement in ovariectomized rodents can lead to enhanced novelty preference. The present study aimed to determine: 1) whether the effect of E on NOP performance is the result of enhanced preference for novelty, per se, or facilitated object-recognition memory, and 2) whether E affects NOP performance through actions it has within the perirhinal cortex/entorhinal cortex region (PRh/EC). Ovariectomized rats received either systemic chronic low 17-β estradiol (E2; ~ 20 pg/ml serum) replacement alone or in combination with systemic acute high administration of estradiol benzoate (EB; 10 μg), or in combination with intracranial infusions of E2 (244.8 pg/μl) or vehicle into the PRh/EC. For one of the intracranial experiments, E2 was infused either immediately before, immediately after, or 2 h following the familiarization (i.e., learning) phase of the NOP test. In light of recent evidence that raises questions about the internal validity of the NOP test as a method of indexing object-recognition memory, we also tested rats on a delayed nonmatch-to-sample (DNMS) task of object recognition following systemic and intra-PRh/EC infusions of E2. Both systemic acute and intra-PRh/EC infusions of E enhanced novelty preference, but only when administered either before or immediately following familiarization. In contrast, high E (both systemic acute and intra-PRh/EC) impaired performance on the DNMS task. The findings suggest that while E2 in the PRh/EC can enhance novelty preference, this effect is probably not due to an improvement in object-recognition abilities.     

Comparative effects of β-carotene and fucoxanthin on retinol deficiency induced oxidative stress in rats

This study aimed at comparing antioxidant potential of fucoxanthin (FUCO) with β-carotene in relieving lipid peroxidation (Lpx) caused by retinol deficiency (RD) in rats. RD rats (n = 45) were fed a dose of either β-carotene (0.81 μmol) or FUCO (0.83 μmol). Plasma and liver lipid peroxide levels and activity of antioxidant enzymes catalase (CAT) and glutathione transferase (GST) were measured for 8 h. Results revealed that RD increased (P < 0.05) Lpx in plasma and liver by 34.3% and 19.4%, while the CAT activity in plasma (89%) and liver microsomes (91%) and GST in liver homogenate (31%) and liver microsomes (30%) were decreased (P < 0.05) compared to control (rats fed basal diet). FUCO suppressed (P < 0.05) the Lpx level by 7–85% (plasma) and 24–72% (liver) as compared to β-carotene (51–76%, 33–65%) over a period of 8 h. The activity of CAT in plasma and liver microsomes was higher (P < 0.05) in FUCO (90–95%, 85–93%) and β-carotene (87–96%, 79–91%) groups as compared to RD group. Similarly, the activity of GST in liver and its microsomes was also elevated (P < 0.05) in FUCO (44–51%, 22–51%) and β-carotene (19–54%, 30–43%) groups as compared to RD group. Results demonstrate that FUCO has greater potential than β-carotene in modulating Lpx, CAT, GST in plasma and liver of RD rats.     

Effects of α lipoic acid on noise induced oxidative stress in rats

This study was conducted to identify how exposure to ambient noise that is over 75 dB affects the oxidant-antioxidant profile using hematological and biochemical indicators, and to investigate the effects of a strong and current antioxidant, $\alpha$ lipoic acid, on rats that were subjected to noise stress. For this purpose, five groups of eight rats were formed as follows: Control (K), Noise Exposure (GK), Lipoic Acid (LA), Noise Pollution + $\alpha$Lipoic Acid (GK + LA) and Oil (Y). The blood samples collected from rats were analyzed and MDA (malondialdehyde), GSH (glutathione), SOD (superoxide dismutase), CAT (catalase), NO (nitrit oxide), GPx (glutathione peroxidase), leukocytes, monocytes, lymphocytes, erythrocytes, hemoglobin, hematocrit, glucose, cholesterol, total protein, triglycerides, HDL (high density lipoprotein), LDL (low density lipoprotein), and urea-N levels were measured. The physical factory environment in a textile factory was preferred to simulate the noise exposure. Ambient noise was measured to be 75 dB. Exposure to physical ambient noise was sustained for 30 days. MDA level was measured at the lowest level in the LA and GKLA groups while it was statistically significantly higher in other groups than it was in the control group. It was observed that GSH reached its lowest level in the group that was exposed to noisy environment, the 100 mg/kg/day $\alpha$lipoic acid administered on the experimental model increased this level to that of the control group and this change was statistically significant (p < 0.05). Considering the urea levels, the increases in GK and GKLA groups and the decreases in LA and Y groups were observed to be statistically significant. When glucose levels were compared to the control group, they were found to be statistically significantly lower in all groups. As a result, it was observed that exposure to noise for 30 days was likely to lead to leukocyte-based immune deficiency and using $\alpha$ lipoic acid as an antioxidant might provide a significant protection against the noise stress.     

Protective effects of curcumin against lithium–pilocarpine induced status epilepticus,cognitive dysfunction and oxidative stress in young rats

Status epilepticus (SE), one of the most severe forms of epilepsy is regarded a medical emergency with considerable morbidity and mortality. Due to the limited efficacy and enormous side effects of currently available drugs, a search for new safe and effective therapeutic agents is critical using experimentally induced SE in animals. The lithium–pilocarpine (Li–Pc) model of SE is most suitable and frequently used for pathophysiological and management strategies of SE. Recent studies have shown significant potential of pharmacological, prophylactic or therapeutic use of curcumin (Cur) in many beneficial activities in the body including neuroprotection in neurodegenerative diseases and antioxidant properties. The present study describes anticonvulsive effects of Cur in Li–Pc induced SE in young rats. The effect of Cur was examined on the intensity and frequency of SE, cognitive behavior in water maze as well as on oxidative stress related enzymes in the brain. Besides its anticonvulsant effect, Cur significantly ameliorates SE-induced cognitive dysfunction and oxidative damages in the hippocampus and striatum areas of the brain. Possible therapeutic application of Cur as an anticonvulsant and as an antioxidant for the treatment of SE has a great potential and warrants further studies.     

Activation of ERα is necessary for estradiol's anorexigenic effect in female rats

While there is considerable evidence that the ovarian hormone estradiol reduces food intake in female rats, it is unclear which estrogen receptor (ER) subtype, ERα or ERβ, mediates this effect. While several studies have demonstrated that activation of ERα, but not ERβ, is sufficient to reduce food intake in ovariectomized (OVX) rats, there are limited data regarding which receptor subtype is necessary. Here we used the selective ERα and ERß antagonists, MPrP and PHTPP, respectively, to investigate this question. We found that antagonism of ERα, but not ERβ, prevented the decrease in food intake following acute administration of estradiol in OVX rats. In addition, antagonism of ERα prevented the estrous-related, phasic reduction in food intake that occurs in response to the rise in circulating levels of estradiol in cycling rats. We conclude that activation of ERα is necessary for the anorexigenic effects of exogenous and endogenous estradiol in female rats.     

Cimicifuga racemosa impairs fatty acid β-oxidation and induces oxidative stress in livers of ovariectomized rats with renovascular hypertension

The aim of this work was to evaluate the effects of therapeutic doses of Cimicifuga racemosa on cardiovascular parameters and on liver lipid metabolism and redox status in an animal model of estrogen deficiency associated with hypertension, a condition that could make the liver more vulnerable to drug-induced injuries. Female Wistar rats were subjected to the surgical procedures of bilateral ovariectomy (OVX) and induction of renovascular hypertension (two-kidneys, one-clip; 2K1C). These animals (OVX + 2K1C) were treated with daily doses of a C. racemosa extract, using a dose that is similar to that recommended to postmenopausal women (0.6mg/kg), over a period of 15 days. The results were compared to those of untreated OVX + 2K1C, OVX, and control rats. The treatment with C. racemosa caused a significant reduction in blood pressure. In the liver, treatment did not prevent the development of steatosis, and it reduced the mitochondrial and peroxisomal capacity to oxidize octanoyl-CoA compared to the untreated animals. In addition, C. racemosa caused numerous undesirable effects on the liver redox status: it increased the mitochondrial reactive oxygen species generation, an event that was not accompanied by an increase in the activity of superoxide dismutase, and it induced a decrease in peroxisomal catalase activity. Although the reduced glutathione content had not been affected, a phenomenon that probably reflected the restoration of glucose-6-phosphate dehydrogenase activity by C. racemosa, oxidative damage was evidenced by the elevated level of thiobarbituric acid-reactive substances found in the liver of treated animals.     

Protective effect of 17β-estradiol on oxidative stress and liver dysfunction in aged male rats

In aging liver oxidative stress increases due to the decrease in antioxidant bio-molecules such as estrogens which can be modified by hormonal replacement therapy (HRT). With this in mind, we hypothesized that age-related decline in steroidogenesis may be associated with the impairment of the antioxidant defense cells in liver, the increase in lipid peroxidation, hepatic dysfunction and histological changes; estrogens prevent all these changes induced by aging. 17beta-estradiol treatment was initiated in 12 month-old Wistar rats, and continued until 18 months of age. Our results showed that 17beta-estradiol (E2) level in the serum of the aged untreated rats was reduced by -32% in 18 month-old rats compared to the young animals (4-month-old). The superoxide dismutase (SOD), catalase (CAT), and gluthatione peroxidase (GPX) activities were reduced by -47, -46, and -29% respectively in old rat liver. In addition, the TBARs in liver and hepatic dysfunction parameters in plasma such as gamma-glutamyl transferase (GGT), phosphatase alkalin (PAL) as well as bilirubin level increased significantly in old rats, and histological changes were investigated. In E2-treated rats, protective effects were observed. Indeed, 17beta-estradiol attenuates all changes induced by aging. The 17beta-estradiol level was higher in old E2-treated rats compared to the control rats. Moreover, the SOD, CAT and GPX activities were higher by +28, +15, and +11% respectively. This anti-aging effect of estrogens was clarified by a lower level of lipid peroxidation and liver dysfunction parameters as well as by histological observation.     

Estrogen improved metabolic syndrome through down-regulation of VEGF and HIF-1α to inhibit hypoxia of periaortic and intra-abdominal fat in ovariectomized female rats

Metabolic syndrome (MBS), a cluster of metabolic abnormalities and visceral fat accumulation, increases cardiovascular risks in postmenopausal women. In addition to visceral fat, perivascular adipose tissue has been recently found to play an important role in vascular pathophysiology. Hence, the present study investigates the effects of estrogen on both intra-abdominal fat (visceral fat) and periaortic fat (perivascular fat) accumulation as well as hypoxia in ovariectomized female rats. Female rats were divided into sham operation, ovariectomy and ovariectomy with 17β-estradiol supplementation groups. Twelve weeks later, we found that estrogen improved MBS via reducing body weight gain, the weight of periaortic and intra-abdominal fat, hepatic triglyceride, and total serum cholesterol levels. Estrogen also increased insulin sensitivity through restoring glucose and serum leptin levels. For periaortic fat, western blot showed estrogen inhibited hypoxia by reducing the levels of VEGF and HIF-1α, which is consistent with the results from immunohistochemical staining. The correlation analysis indicated that perivascular fat had a positive correlation with body weight, intra-abdominal fat or serum total cholesterol, but a negative correlation with insulin sensitivity index. For intra-abdominal fat, real-time fluorescent RT-PCR showed estrogen improved fat dysfunction via reducing the levels of relative leptin, MCP-1 but increasing adiponectin mRNA. Estrogen reduced the levels of VEGF and HIF-1α to inhibit hypoxia but restored the levels of PPARγ and Srebp-1c, which are important for lipid capacity function of intra-abdominal fat. These results demonstrated estrogen improved MBS through down-regulating VEGF and HIF-1α to inhibit hypoxia of periaortic and intra-abdominal fat in ovariectomized female rats.     

Radioprotective effect of Curcuma longa extract on γ-irradiation-induced oxidative stress in rats

This study was conducted to evaluate the modulatory effect of aqueous extract of Curcuma longa (L.) against γ-irradiation (GR), which induces biochemical disorders in male rats. The sublethal dose of GR was determined in primary hepatocytes. Also, the effect of C.?longa extract was examined for its activity against GR. In rats, C.?longa extract was administered daily (200?mg/kg body mass) for 21?days before, and 7?days after GR exposure (6.5 Gy). The lipid profile and antioxidant status, as well as levels of transaminases, interleukin-6 (IL-6), and tumour necrosis factor?α (TNFα) were assessed. The results showed that in hepatocytes, the aqueous extract exhibited radioprotective activity against exposure to GR. Exposure of untreated rats to GR resulted in transaminase disorders, lipid abnormalities, elevation of lipid peroxidation, trace element alterations, release of IL-6 and TNF, and decrease in glutathione and protein level of superoxide dismutase-1 (SOD-1) and peroxiredoxin-1 (PRDX-1). However, treatment of rats with this extract before and after GR exposure improved antioxidant status and minimized the radiation-induced increase in inflammatory cytokines. Changes occurred in the tissue levels of trace elements, and the protein levels of SOD-1 and PRDX-1 were also modulated by C.?longa extract. Overall, C.?longa exerted a beneficial radioprotective effect against radiation-induced oxidative stress in male rats by alleviating pathological disorders and modulating antioxidant enzymes.     

Changes in hypothalamic–pituitary–adrenal stress responsiveness before and after puberty in rats

This article is part of a Special Issue “Puberty and Adolescence”.     

Thymoquinone ameliorates chemical induced oxidative stress and β-cell damage in experimental hyperglycemic rats

The present study was aimed to investigate the effect of thymoquinone (TQ) on pancreatic insulin levels, tissue antioxidant and lipid peroxidation (LPO) status in streptozotocin (STZ) nicotinamide (NA) induced diabetic rats. Diabetes was induced in experimental rats by a single intraperitoneal (i.p) injection of STZ (45 mg/kg b.w) dissolved in 0.1 mol/L citrate buffer (pH 4.5), 15 min after the i.p administration of NA (110 mg/kg b.w). Diabetic rats exhibited increased blood glucose with significant decrease in plasma insulin levels. The activities of antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and the levels of low-molecular weight antioxidants Vitamin C, Vitamin E and reduced glutathione (GSH) were decreased while increases in the levels of lipid peroxidation markers were observed in liver and kidney tissues of diabetic control rats as compared to control rats. In addition, diabetic rats showed an obvious decrease in pancreatic insulin levels. Administration of TQ (80 mg/kg b.w) to diabetic rats for 45 days significantly reversed the damage associated with diabetes. Biochemical findings were supported by histological studies. These results indicated that TQ exerts a protective action on pancreatic beta cell function and overcomes oxidative stress through its antioxidant properties.     

Tissue specific localization of angiotensin-(1–7) and its receptor Mas in the uterus of ovariectomized rats

The vasoactive peptide angiotensin (Ang)-(1–7) has vasodilator, antifibrotic and antihypertrophic properties, but little is known about its regulation in the uterus. The aim of this study was to evaluate Ang-(1–7) and its receptor Mas expression throughout rat uterine tissues, in ovariectomized animals treated with estrogen alone or combined with progestin. Adult Wistar rats (n?=?19) were ovariectomized and randomly assigned into three different groups 1?week later. One group received a single dose of estradiol benzoate (1.5?mg/kg, i.m. injection, n?=?6). Another group received estradiol associated with depot medroxyprogesterone acetate (3?mg/kg, i.m. injection, n?=?6). Control group (n?=?7) received oil injection. One week later, the rats were euthanized and their uteri were fixed and stained by immunohistochemistry, using a polyclonal antibody specific to Ang-(1–7) and its receptor Mas. Ang-(1–7) was detected in all uterine tissues, but it was weak or absent in the circular myometrium of treated animals. The intensity of the immunostaining decreased in the glandular epithelium of hormonally treated animals when compared to controls. In estrogen treated rats, Ang-(1–7) labeling was scattered and sometimes included the nuclei of glandular cells. We also detected Ang-(1–7) expression in longitudinal myometrium and uterine serosa. Mas receptor was present in all tissues with similar intensity among the tissue types in the control and estrogen plus progestin groups. In the estrogen group, Mas staining was stronger in the luminal and glandular epithelium when compared with stroma or circular myometrium. In conclusion, ovarian steroids are not required to allow endometrial expression of Ang-(1–7) and its receptor Mas in rats, as it remains abundant in ovariectomized animals. However, estrogen and progestin may modulate the distribution pattern of this peptide in the endometrium, especially in the glandular compartment.     

The renin–angiotensin system plays a major role in voiding dysfunction of ovariectomized rats

Aims

The renin–angiotensin system (RAS) plays a major role in cardiovascular diseases in postmenopausal women, but little is known about its importance to lower urinary tract symptoms. In this study we have used the model of ovariectomized (OVX) estrogen-deficient rats to investigate the role of RAS in functional and molecular alterations in the urethra and bladder.

Main methods

Responses to contractile and relaxant agents in isolated urethra and bladder, as well as cystometry were evaluated in 4-month OVX Sprague–Dawley rats. Angiotensin-converting enzyme activity and Western blotting for AT1/AT2 receptors were examined.

Key findings

Cystometric evaluations in OVX rats showed increases in basal pressure, capacity and micturition frequency, as well as decreased voiding pressure. Angiotensin II and phenylephrine produced greater urethral contractions in OVX compared with Sham group. Carbachol-induced bladder contractions were significantly reduced in OVX group. Relaxations of urethra and bladder to sodium nitroprusside and BAY 41-2272 were unaffected by OVX. Angiotensin-converting enzyme activity was 2.6-fold greater (p < 0.05) in urethral tissue of OVX group, whereas enzyme activity in plasma and bladder remained unchanged. Expressions of AT1 and AT2 receptors in the urethra were markedly higher in OVX group. In bladder, AT1 receptors were not detected, whereas AT2 receptor expression was unchanged between groups. 17β-Estradiol replacement (0.1 mg/kg, weekly) or losartan (30 mg/kg/day) largely attenuated most of the alterations seen in OVX group.

Significance

Prolonged estrogen deprivation leads to voiding dysfunction and urethral hypercontractility that are associated with increased ACE activity and up-regulation of angiotensin AT1/AT2 receptor in the urethral tissue.     

Novel effect of α-lactalbumin on the yohimbine-induced hot flush increase of the tail skin temperature in ovariectomized rats

5-Hydroxytryptamine (5-HT) and noradrenaline have been thought to play important roles in the mechanism of hot flush. Then, to clarify the relation between serotonergic and adrenergic nervous systems on the mechanism of hot flush, the effect of paroxetine, 5-HT reuptake inhibitor (SSRI) was evaluated on the yohimbine-induced hot flush increase of tail skin temperature in ovariectomized female rats. Yohimbine (adrenaline α₂ antagonist) significantly increased the tail skin temperature in course of time. Clonidine (adrenaline α₂ agonist) significantly attenuated this effect. Paroxetine also significantly inhibited the increase of tail skin temperature by yohimbine. α-Lactalbumin having SSRI activity in vitro study also significantly inhibited the increase of tail skin temperature, but not significantly decreased the initial temperature. This difference may explain the different mechanism between paroxetine (SSRI) and α-lactalbumin, suggesting new mechanism of hot flush.     

The effect of 17β-estradiol treatment on the mass and the turnover of bone in ovariectomized rats taking a mild dose of thyroxin

We performed the dosing experiment to establish whether estrogen administration has any beneficial effects on the mass and the turnover of bone in ovariectomized rats taking a mild dose of thyroxin. Thirty-five Wistar rats, 28 weeks of age, received ovariectomies (OVX) or sham operations and were divided into five groups. Group I was the sham group, Groups 2–5 were ovariectomized. Group 2 was the OVX-control, Group 3 treated with thyroxin 30 μg/kg/day (T4), Group 4, 17β-estradiol 0.3 mg/kg/week (E2), and Group 5, the combination of T4 and E2. The duration of the experiment was 12 weeks. At the end of the experiment, serum chemistries were measured. Bone minerals in the femur were determined with single photon absorptiometry and bone turnover was assessed histomorphometrically. Alkaline-phosphatase increased in Group 3 (OVX-T4), but it reduced in Groups 4 (OVX-E2) and 5 (OVX-T4 + E2). Bone minerals decreased in Groups 2 (OVX) and 3. In Group 4, it was preserved at the same level as in Group 1. Group 5 showed a significant increase of bone mass compared with Group 1. Eroded surface and osteoid surface increased in Groups 2 and 3 and they were reduced in Groups 4 and 5. Bone volume and mineral apposition rate were at a maximum in Group 5. This study demonstrated that 17β-estradiol was capable of preventing the bone mass decrease by regulating the turnover in ovariectomized rats taking a mild dose of thyroxin. Osteoblast function appeared to be stimulated in combination with 17β-estradiol and thyroxin.