Protective Effect Of 17β-estradiol Research Articles

The protective effects of 17-β estradiol and SIRT1 against cardiac hypertrophy: a review.

One of the major causes of morbidity and mortality worldwide is cardiac hypertrophy (CH), which leads to heart failure. Sex differences in CH can be caused by sex hormones or their receptors. The incidence of CH increases in postmenopausal women due to the decrease in female sex hormone 17-β estradiol (E2) during menopause. E2 and its receptors inhibit CH in humans and animal models. Silent information regulator 1 (SIRT1) is a NAD+-dependent HDAC (histone deacetylase) and plays a major role in biological processes, such as inflammation, apoptosis, and oxidative stress responses. Probably SIRT1 because of these effects, is one of the main suppressors of CH and has a cardioprotective effect. On the other hand, estrogen and its agonists are highly efficient in modulating SIRT1 expression. In the present study, we review the protective effects of E2 and SIRT1 against CH.

17β-Estradiol Protects Neural Stem/Progenitor Cells Against Ketamine-Induced Injury Through Estrogen Receptor β Pathway.

Ketamine inhibits neural stem/progenitor cell (NSPC) proliferation and disrupts normal neurogenesis in the developing brain. 17β-Estradiol alleviates neurogenesis damage and enhances behavioral performance after ketamine administration. However, the receptor pathway of 17β-estradiol that protects NSPCs from ketamine-induced injury remains unknown. In the present study, we investigated the role of estrogen receptor α (ER-α) and estrogen receptor β (ER-β) in 17β-estradiol’s protection against ketamine-exposed NSPCs and explored its potential mechanism. The primary cultured NSPCs were identified by immunofluorescence and then treated with ketamine and varying doses of ER-α agonist 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (PPT) or ER-β agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) for 24 h. NSPC proliferation was analyzed by 5-bromo-2-deoxyuridine incorporation test. The expression of phosphorylated glycogen synthase kinase-3β (p-GSK-3β) was quantified by western blotting. It was found that treatment with different concentrations of PPT did not alter the inhibition of ketamine on NSPC proliferation. However, treatment with DPN attenuated the inhibition of ketamine on NSPC proliferation at 24 h after their exposure (P < 0.05). Furthermore, treatment with DPN increased p-GSK-3β expression in NSPCs exposed to ketamine. These findings indicated that ER-β mediates probably the protective effects of 17β-estradiol on ketamine-damaged NSPC proliferation and GSK-3β is involved in this process

Fenton Reaction-Induced Oxidative Damage to Membrane Lipids and Protective Effects of 17β-Estradiol in Porcine Ovary and Thyroid Homogenates.

The Fenton reaction (Fe2++H2O2→Fe3++•OH+OH-) results in strong oxidative damage to macromolecules when iron (Fe) or hydrogen peroxide (H2O2) are in excess. This study aims at comparing Fe2++H2O2-induced oxidative damage to membrane lipids (lipid peroxidation, LPO) and protective effects of 17β-estradiol (a potential antioxidant) in porcine ovary and thyroid homogenates. Iron, as one of the Fenton reaction substrates, was used in the highest achievable concentrations. Thyroid or ovary homogenates were incubated in the presence of: (1st) FeSO4+H2O2 with/without 17β-estradiol (1 mM; 100, 10.0, 1.0 µM; 100, 10.0, 1.0 nM; 100, 10.0, 1.0 pM); five experiments were performed with different FeSO4 concentrations (2400, 1200, 600, 300, 150 µM); (2nd) FeSO4 (2400, 1200, 600, 300, 150 µM)+H2O2 with/without 17β-estradiol; three experiments were performed with three highest 17β-estradiol concentrations; (3rd) FeSO4 (2400, 1200, 1100, 1000, 900, 800, 700, 600, 300, 150, 75 µM)+H2O2 (5 mM). LPO level [MDA+4-HDA/mg protein] was measured spectrophotometrically. The basal LPO level is lower in ovary than in thyroid homogenates. However, experimentally-induced LPO was higher in the former tissue, which was confirmed for the three highest Fe2+ concentrations (2400, 1200, 1100 µM). Exogenous 17β-estradiol (1 mM, 100, and 10 µM) reduced experimentally-induced LPO independently of iron concentration and that protective effect did not differ between tissues. The ovary, compared to the thyroid, reveals higher sensitivity to prooxidative effects of iron, however, it showed similar responsivity to protective 17β-estradiol activity. The therapeutic effect of 17β-estradiol against iron overload consequences should be considered with relation to both tissues.

Protective Effects of 17β-Estradiol on Hippocampal Myelinated Fibers in Ovariectomized Middle-aged Rats

Estrogen replacement therapy (ERT) improves hippocampus-dependent cognition. This study investigated the impact of estrogen on hippocampal volume, CA1 subfield volume and myelinated fibers in the CA1 subfield of middle-aged ovariectomized rats. Ten-month-old bilaterally ovariectomized (OVX) female rats were randomly divided into OVX + E2 and OVX + Veh groups. After four weeks of subcutaneous injection with 17β-estradiol or a placebo, the OVX + E2 rats exhibited significantly short mean escape latency in a spatial learning task than that in the OVX + Veh rats. Using stereological methods, we did not observe significant differences in the volumes of the hippocampus and CA1 subfields between the two groups. However, using stereological methods and electron microscopy techniques, the total length of myelinated fibers and the total volumes of myelinated fibers, myelin sheaths and myelinated axons in the CA1 subfields of OVX + E2 rats were significantly 38.1%, 34.2%, 36.1% and 32.5%, respectively, higher than those in the OVX + Veh rats. After the parameters were calculated according to different diameter ranges, the estrogen replacement-induced remodeling of myelinated fibers in CA1 was mainly manifested in the myelinated fibers with a diameter of <1.0 μm. Therefore, four weeks of continuous E2 replacement improved the spatial learning capabilities of middle-aged ovariectomized rats. The E2 replacement-induced protection of spatial learning abilities might be associated with the beneficial effects of estrogen on myelinated fibers, particularly those with the diameters less than 1.0 μm, in the hippocampal CA1 region of middle-aged ovariectomized rats.

Protective Effects of 17β-Estradiol on Benzo(e) pyrene[B(e)P]-induced Toxicity in ARPE-19 cells.

Purpose:The aim of this study was to examine the effect of 17β-estradiol on Benzo(e)pyrene [B(e)P]-induced toxicity in ARPE-19 cells.Methods:We pretreated ARPE-19 cells with 20 nM and 40 nM 17β-estradiol for 6 hours, followed by addition of 300 μM B(e)P for additional 24 hours. Cell viability was measured using Trypan blue dye-exclusion assay. JC-1 assay was performed to measure mitochondrial membrane potential (ΔΨm). For a quantitative estimation of cell death, apoptotic markers such as caspase-3/7, caspase-9, and caspase-12 were measured.Results:Our results demonstrated that when treated with B(e)P, the viability and ΔΨm of ARPE-19 cells declined by 25% and 63%, respectively (P < 0.05). However, pretreating with 17β-estradiol increased the viability of ARPE-19 cells by 21% (20 nM) and 10% (40 nM) (P < 0.05). Furthermore, the significantly reduced ΔΨm in βE+B(e)P treated cells ARPE-19 cells was restored by pre-treatment with 17β-estradiol- ΔΨm was increased by 177% (20 nM) and 158% (40 nM) (P < 0.05). We further observed a significant up-regulation in the activity of Caspases-3/7, -9, and -12 in B(e)P-treated ARPE-19 cells. However, 17β-estradiol treatment significantly reduced the activity of all apoptotic markers (P < 0.05).Conclusion:In conclusion, our results demonstrate that 17β-estradiol protects ARPE-19 cells against B(e)P-induced toxicity by decreasing apoptosis, preventing cell death, and restoring mitochondrial membrane potential.

Protective effects of 17β-estradiol on high glucose-induced RPE cells

Protective effects of 17β-estradiol on high glucose-induced RPE cells

Huntingtin polyQ Mutation Impairs the 17β-Estradiol/Neuroglobin Pathway Devoted to Neuron Survival.

Among several mechanisms underlying the well-known trophic and protective effects of 17β-estradiol (E2) in the brain, we recently reported that E2 induces the up-regulation of two anti-apoptotic and neuroprotectant proteins: huntingtin (HTT) and neuroglobin (NGB). Here, we investigate the role of this up-regulation. The obtained results indicate that E2 promotes NGB-HTT association, induces the localization of the complex at the mitochondria, and protects SK-N-BE neuroblastoma cells and murine striatal cells, which express wild-type HTT (i.e., polyQ7), against H2O2-induced apoptosis. All E2 effects were completely abolished in HTT-knocked out SK-N-BE cells and in striatal neurons expressing the mutated form of HTT (mHTT; i.e., polyQ111) typical of Huntington's disease (HD). As a whole, these data provide a new function of wild-type HTT which drives E2-induced NGB in mitochondria modulating NGB anti-apoptotic activity. This new function is lost by HTT polyQ pathological expansion. These data evidence the existence of a novel E2/HTT/NGB neuroprotective axis that may play a relevant role in the development of HD therapeutics.

Molecular mechanisms involved in the protective effect of 17β-estradiol and testosterone against apoptosis in skeletal muscle cells

Molecular mechanisms involved in the protective effect of 17β-estradiol and testosterone against apoptosis in skeletal muscle cells

Protective effect of 17β-estradiol on serum deprivation-induced apoptosis and oxidative stress in bone marrow-derived mesenchymal stem cells.

Stem cell transplantation has indicated great promise for cell therapy in a wide range of diseases, but poor and insufficient viability of cells within damaged tissues has limited its potential therapeutic effects. 17 β-Estradiol (E2) is a steroid hormone that plays an important role in expression of many genes and regulating proliferation, viability, and intracellular redox status in different cell types. In this study, we aimed to assess the effect of E2 on bone marrow-derived mesenchymal stem cells (BM-MSCs). Apoptosis was induced by serum deprivation (SD), and cells were exposed to E2 in the presence or absence of serum for varying periods of time, after which cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Expression of proapoptotic and antiapoptotic proteins after exposure to E2 was examined by Western blotting. The ability of E2 to prevent reactive oxygen species (ROS) production was also measured. The results indicated that E2 significantly enhanced the viability of the cells and protected BM-MSCs against SD-induced overproduction of ROS. It could reduce lipid peroxidation, total antioxidant power, and also Bax/Bcl-2 ratio as well as expression of caspase-3. Taken together, our data support that E2 treatment protects BM-MSCs against SD-induced damage by regulating ROS production and upregulation of antiapoptotic/proapoptotic proteins ratio.

Neuroprotective effects of 17β-estradiol associate with KATP in rat brain

Previous studies have indicated that estrogen protects the brain from ischemic damage and regulates K(ATP) channel activity; the present study was designed to address the involvement of K(ATP) channels in the neuroprotective effects of estrogen in focal cerebral ischemia: in experiment 1, K(ATP) mRNA and protein in the cortices of rats were compared among groups of ovariectomized rats (Ovx-1), Sham-operated rats (Sham-1), and ovariectomized rats administered 17β-estradiol (Estr-1). In experiment 2, neurobehavioral scores and infarct volume of rats were evaluated after middle cerebral artery occlusion in ovariectomized rats (Ovx-2), Sham-operated rats (Sham-2), ovariectomized female rats administered 17β-estradiol (Estr-2), and ovariectomized rats administered both 17β-estradiol and stereotactic injections of glibenclamide (Estr+G). Our results showed that the Kir6.2 and SUR1 mRNA and protein levels in the brain cortices of female ovariectomized rats were lower than those in Sham rats. However, the expression levels of Kir6.2 and SUR1 in brain cortices of ovariectomized rats recovered after supplementation with 17β-estradiol. The protective effects of 17β-estradiol were abolished by glibenclamide, a K(ATP) channel blocker. This indicates that estradiol significantly upregulates the expression of K(ATP) channel subunits and channel activity in the brain cortices of ovariectomized rats. This regulation is associated with the neuroprotective effects of estradiol.

Protective effect of 17β-estradiol on ischemic acute kidney injury through the renal sympathetic nervous system

Enhanced renal sympathetic nerve activity during an ischemic period and renal venous norepinephrine overflow after reperfusion play important roles in the development of ischemic acute kidney injury. In this study, we examined the effect of 17β-estradiol on the renal sympathetic nervous system and kidney function in ischemia/reperfusion-induced acute kidney injury in anesthetized rats. Ischemic acute kidney injury was induced by clamping the left renal artery and vein for 45min followed by reperfusion, 2weeks after a contralateral nephrectomy. Intravenous injection of 17β-estradiol (100μg/kg) 15min before reperfusion suppressed enhanced renal sympathetic nerve activity during renal ischemia, also suppressed renal venous norepinephrine overflow after reperfusion, and attenuated ischemia/reperfusion-induced renal dysfunction with histological damage. The above renoprotective effects of 17β-estradiol were reversed by pretreatment with tamoxifen (5mg/kg), an estrogen receptor antagonist, or NG-nitro-L-arginine methyl ester (0.3mg/kg), a non-selective nitric oxide synthase inhibitor. These results indicate that 17β-estradiol can suppress enhanced renal sympathetic nerve activity during renal ischemia, and its consequent effect on norepinephrine overflow from nerve endings, by nitric oxide production via estrogen receptors. These effects appear to contribute to renoprotection against ischemia/reperfusion-induced renal injury.

The protective effect of 17β-estradiol against hydrogen peroxide-induced apoptosis on mesenchymal stem cell

This study was designed to investigate the function of 17β-estradiol (17β-E2) against oxidative stress on the cell death of mice bone marrow mesenchymal stem cells (BMSCs) induced by hydrogen peroxide (H2O2). BMSCs were treated with 17β-E2 for 24h and then treated with 100μM H2O2 for 1h. Cell viability, apoptosis, caspase-9 mRNA, JNKs (Jun N-terminal kinases) and c-Jun protein expression in BMSCs were evaluated. Cell apoptosis of BMSCs were increased in a dose-dependent manner after treated with H2O2 compared to control group. But pretreatment with 17β-E2 can inhibit apoptosis of BMSCs, preserve the mitochondrial transmembrane potential, decrease caspase-9 mRNA, JNK1/2 and c-Jun protein expression. In conclusion, 17β-E2 exerts antiapoptotic effects in BMSCs which related to the mitochondria death pathway and JNKs pathway. The study revealed that 17β-E2 can reduce the donor stem cells damage.

17 β-estradiol protects the liver against ischemia reperfusion injury in rat liver transplantation GAO

Objective To investigate the protective effects of 17β-estradiol on ischemia reperfusion injury in rat liver transplantation. Methods The rats were divided into three groups: male to male group(MG), female to female group (FG), and male to male group which were given 17β-estradiol 4000 μg/kg 24 hours before liver transplantation intraperitoneally (M + EG). Then transplantation was performed. At 6 hours after portal vein reperfusion, blood samples were obtained to determine the levels of alanine aminotransferase(ALT), aspartate aminotransferase (AST), and nitric oxide(NO). The expression of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in liver were observed by immunohistochemistry. Results ALT and AST levels in the M+EG group were lower than those in MG and FG (561. 69 U/L vs 730. 78 U/L and 678. 82 U/L; 726. 44 U/L vs 914. 21 U/L and 861. 86 U/L). The NO level (63. 54 μmol/L) was much higher than those in the MG and FG groups. The expression of eNOS in the M+EG group was higher than those in MG and FG, while the expression of iNOS in M+EG were lower than those in MG. and FG. Conclusion 17β-estradiol can attenuate ischemia reperfusion injury in rat liver transplantation by improving the balance of eNOS and iNOS. Key words: Estradiol; Liver transplantation; Ischemia reperfusion injury; Nitric oxide synthase

Effects of estrogen on AF64A-induced apoptosis in NG108-15 cells

In this study, we show that pretreatment with physiological concentrations (1–100 nM) of 17β-estradiol decreased apoptosis induced by ethylcholine aziridinium (AF64A), a choline toxin, in the cholinergic neuronal cell line NG108-15. These protective effects were observed after short-term (30 min) pretreatment, and were blocked by treatment with an estrogen receptor antagonist and inhibitors of phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase kinase (MEK). The protective effects were, however, not reversed by a protein synthesis inhibitor. Furthermore, we examined the effects of 17β-estradiol on choline uptake in NG108-15 cells. Although choline uptake was inhibited by a selective inhibitor of choline uptake, hemicholinium-3, it was not altered by treatment with 17β-estradiol. These results indicated that the protective effect of 17β-estradiol on AF64A-induced apoptosis could be nongenomic, and that this effect may be due to the activation of PI3K/Akt and/or MEK/extracellular signal-regulated kinase (ERK) pathways.

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.

The Protective Effects of 17β-Estradiol on Hepatic Ischemia–Reperfusion Injury in Rat Model, Associated with Regulation of Heat-Shock Protein Expression

Ischemia-reperfusion (I/R) injury, which was commonly seen in the field of hepatic surgical intervention, impaired liver regeneration and predisposed to liver failure. Previous studies have shown gender dimorphic response of the liver for various hepatic stresses including I/R injury, hemorrhagic shock-resuscitation, liver cirrhosis, endotoxemia, and chronic alcoholic consumption, and demonstrated gender dimorphism in hepatocellular dysfunction after experimental trauma and hemorrhage. The objective of this study was to examine the hypothesis that the protective effects of 17beta-estradiol (E2) in hepatic I/R injury were associated with increasing heat-shock protein 70 expression. Sprague-Dawley male and female rats were randomly divided into male and female sham, I/R, and E2 + I/R groups. The model of reduced-size liver ischemia and reperfusion was used. Except for the sham-operated groups, all rats were subjected to 70% liver ischemia for 45 min followed by resection of the remaining 30% nonischemic lobes and reperfusion of ischemic tissue. For each group, five rats were used to investigate the survival during a week after operation; blood samples and liver tissues were obtained in the remaining animals after 3, 12, and 24 h of reperfusion to assess serum alanine aminotransferase, aspartate aminotransferase, liver tissue NO(2)(-) + NO(3)(-), malondialdehyde content, superoxide dismutase, nitric oxide synthase, and myeloperoxidase activity, Hsp70 expression, and apoptosis ratio. Compared with I/R groups, male and female E2 + I/R groups showed less I/R-induced injury, and SOD and eNOS activity and Hsp70 expression were increased significantly (P < 0.01). A higher rate of apoptosis was observed in the I/R group versus the E2 + I/R group, a significant increase of MDA, NO(2)(-) + NO(3)(-), and MPO of liver tissues and serum transaminase were also observed in the I/R group versus the E2 + I/R group. The survival rate was significantly higher in the male E2 + I/R group than in the male I/R group. E2 pretreatment had protective effects on liver in hepatic I/R injury. The mechanism of this protection might be related to overexpression of Hsp70.

Mitochondria play an important role in 17β-estradiol attenuation of H2O2-induced rat endothelial cell apoptosis

Studies have shown salutary effects of 17beta-estradiol following trauma-hemorrhage on different cell types. 17beta-Estradiol also induces improved circulation via relaxation of the aorta and has an anti-apoptotic effect on endothelial cells. Because mitochondria play a pivotal role in apoptosis, we hypothesized that 17beta-estradiol will maintain mitochondrial function and will have protective effects against H(2)O(2)-induced apoptosis in endothelial cells. Endothelial cells were isolated from rats' aorta and cultured in the presence or absence of H(2)O(2), a potent inducer of apoptosis. In additional studies, endothelial cells were pretreated with 17beta-estradiol. Flow cytometry analysis revealed H(2)O(2)-induced apoptosis in 80.9% of endothelial cells; however, prior treatment of endothelial cells with 17beta-estradiol resulted in an approximately 40% reduction in apoptosis. This protective effect of 17beta-estradiol was abrogated when endothelial cells were cultured in the presence ICI-182780, indicating the involvement of estrogen receptor (ER). Fluorescence microscopy revealed a 17beta-estradiol-mediated attenuation of H(2)O(2)-induced mitochondrial condensation. Western blot analysis demonstrated that H(2)O(2)-induced cytochrome c release from mitochondrion to cytosol and the activation of caspase-9 and -3 were decreased by 17beta-estradiol. These findings suggest that 17beta-estradiol attenuated H(2)O(2)-induced apoptosis via ER-dependent activation of caspase-9 and -3 in rat endothelial cells through mitochondria.

Are the protective effects of 17β-estradiol on splenic macrophages and splenocytes after trauma-hemorrhage mediated via estrogen-receptor (ER)-α or ER-β?

The depression in cell-mediated immune function following trauma-hemorrhage is shown to be restored by 17beta-estradiol (E2) administration. However, it remains unknown which of the two estrogen-receptors, (ER)-alpha or ER-beta, plays the predominant role in mediating the beneficial effects of E2. Female B57BL/J6 ER-beta(-/-) transgenic mice [knockout (KO)] and corresponding ovariectomized wild-type (WT) mice were subjected to laparotomy and hemorrhagic shock (35.0+/-5.0 mmHg for 90 min) and treated with E2 (50 microg/25 g) or ER-alpha agonist propyl pyrazole triol (PPT; 50 microg/25 g) following trauma-hemorrhage. Four hours after resuscitation, systemic cytokine concentrations and cytokine release by splenocytes and splenic macrophages were determined by cytometric bead array. Trauma-hemorrhage resulted in a significant increase in plasma tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, and IL-10. In contrast, the release of these cytokines by splenic macrophages was decreased significantly in WT and KO animals. Administration of E2 or PPT following trauma-hemorrhage produced a significant reduction in systemic TNF-alpha and IL-6 concentrations in WT and KO mice. Although the suppression in the productive capacity of these cytokines following trauma-hemorrhage by macrophages and splenocyte was also prevented in E2- and PPT-treated WT mice, the release of cytokines by macrophages and splenocytes in E2- and PPT-treated KO mice was not restored to the levels observed in sham animals. These findings collectively suggest that both receptors appear to play a significant role in mediating the immunoprotective effects of E2 in different tissue compartments following trauma-hemorrhage.

Protective effects of 17β-estradiol and trivalent chromium on interleukin-6 secretion, oxidative stress, and adhesion of monocytes: Relevance to heart disease in postmenopausal women

Postmenopausal diabetic women are at greater risk for heart disease compared with men of similar age and with other risk factors. We examined the hypothesis that 17β-estradiol and trivalent chromium inhibit secretion of the pro-inflammatory cytokine interleukin (IL)-6 and oxidative stress in monocytes exposed to high glucose (HG). U937 human monocytes were cultured with HG (30 mM) with and without 17β-estradiol (0–1000 nM) and chromium chloride (Cr 3+, 0–10 μM) at 37°C for 24 h. Results show that 17β-estradiol inhibits IL-6 and adhesion to endothelial cells ( p <. 05) by HG-treated monocytes. Treatment with 17β-estradiol+Cr 3+ required a significantly lower dose of estradiol-17β compared with 17β-estradiol alone for IL-6 inhibition. 17β-Estradiol+Cr 3+ also inhibited lipid peroxidation and the adhesivity to human endothelial cells in HG-treated monocytes. Thus, 17β-estradiol+Cr 3+ inhibits oxidative stress, IL-6 secretion, and monocytic adhesion to endothelial cells, risk factors in the development of heart disease. The female body requires E but studies on some patients indicate side effects with increased amounts of 17β-estradiol-supplementation. The potential benefit of a lower estrogen dose in combination with chromium is novel and needs to be explored in postmenopausal diabetic women.

Estradiol’s effect on portal response to endothelin-1 after trauma-hemorrhage

Background The fine balance between vasoconstrictors and vasodilators maintains portal circulation. Studies have shown that portal response to endothelin-1 (ET-1), a potent vasoconstrictor, is enhanced following hemorrhagic-shock, which subsequently leads to the impaired hepatic circulation and hepatic damage. Although protective effects of 17β-estradiol (E 2) against hepatic damage following trauma-hemorrhage have been observed, it remains unknown whether E 2 directly improves hepatic circulation. We hypothesized that the salutary effects of E 2 are mediated, at least in part, by the attenuation of portal response to ET-1 following trauma-hemorrhage. Materials and methods Male adult Sprague-Dawley rats were randomly assigned to sham operation or trauma-hemorrhage with or without in vivo E 2 treatment. Trauma-hemorrhage included midline laparotomy and ∼90 min of hemorrhagic shock (35 mmHg), then resuscitation with four times the shed blood volume with Ringer’s lactate solution over 60 min. For the E 2 treatment group, 1 mg/kg of E 2 was added to the Ringer’s lactate solution. At 5 h after the end of resuscitation, the liver was isolated and perfused in vitro to measure portal pressure responses to exogenous ET-1 (60 pmol in 150 ml perfusate, bolus) with or without E 2 (1,500 pg/ml). Results Peak portal pressure after the administration of ET-1 was significantly higher in vehicle-treated trauma-hemorrhage group compared with the sham group. This effect was significantly attenuated in the E 2 treatment group. Furthermore, E 2 treatment restored bile production and prevented hepatic damage following trauma-hemorrhage. Conclusions The beneficial effects of estradiol observed following trauma-hemorrhage, at least partly, are caused by the attenuation of portal pressure response to increased ET-1.