Estradiol valerate enhances cardiac function via the Nrf2 signaling pathway to protect against oxidative stress by the Nrf2 signaling pathway in an ovariectomized rat model

Background: The increased risk of cardiovascular disease (CVD) in postmenopausal women and ovariectomized patients suggests that estrogen has a protective effect on cardiac function. Oxidative stress is the main cause of CVD, and the cellular defensive Nrf2 antioxidant pathway plays a protective role in various pathologies. However, the regulation of Nrf2 by estrogen has received little attention. Objective: The present study aimed to investigate the role of Nrf2 in the effect of estrogen on the cardiac function. Method:: In the present study, female SD rats were divided into three groups as follows: sham operation (SHAM), bilateral ovariectomy (OVX) and bilateral ovariectomy with estradiol valerate (EV) supplementation (OVX+EV). Vaginal smears and E2 concentrations were used to confirm model success. We compared cardiac morphology and function by echocardiography and HE staining. The levels of oxidative stress markers and antioxidant enzymes as well as protein expression of antioxidant genes were evaluated by Western blotting and immunohistochemistry. Results: Our results showed that supplementation with estrogen restored the parameters to some extent. Left ventricular end diastolic diameter at diastolic （LVID;d） and left ventricular volume at diastolic (LV vol;d) increased but MV E wave/A wave (E/A) significantly decreased. The oxidative stress indicators (malondialdehyde) increased, and the antioxidant activity indicators, such as superoxide dismutase (SOD) and catalase (CAT), decreased. Further, the expression of most Nrf2 antioxidant pathway-related proteins in the heart decreased after ovariectomy. Conclusion: The present study demonstrated that estrogen may protect cardiac function by regulating antioxidant capacity through the Nrf2 pathway.

Genistein acts in bone metabolism and improves peri-implant healing in rats with estrogen deficiency

The present study aimed to evaluate the peri-implantar bone healing in the presence of genistein treatment in ovariectomized rats. Thirty female rats with 4 months old were divided into 3 groups according to the experimental condition and the drug treatment: SHAM (rats submitted to the fictional surgery and gavage with 0.9% saline solution); OVX (rats submitted to bilateral ovariectomy and gavage with 0.9% saline solution); OVX GEN (rats submitted to bilateral ovariectomy and gavage with 1mg/day of genistein). 60 implants were installed, with two implants in each animal. The calcified group was subjected microcomputerized tomography and the parameters analysed was bone volume per tissue volume (BV/TV) and connective density (Cnn.Dn). The decalcified samples were evaluated through immunolabeling analysis, in order to detect the presence of RUNX2, Alkaline Phosphatase, Osteocalcin, Osteopontin and TRAP. All the quantitative data were submitted to the normality curve to determine the most adequate test. The significance level of p<0.05 was considered for all tests. The morphometric analysis of the OVX GEN group showed higher percentage of bone volume and lower connective density when compared with OVX. Immunohistochemical analysis favors expression. For the markers that positively label osteoblastic activity. This study shows that genistein therapy improves peri-implant bone healing in ovariectomized rats.

Oviductal prolapse associated with a leiomyoma in a Hermann’s tortoise (Testudo hermanni)

A twelve-year-old, female Hermann’s tortoise (Testudo hermanni) was presented with an oviductal prolapse after showing tenesmus for three days prior to presentation. Radiography revealed a soft tissue opacity in the caudal coelomic cavity that ultrasonographically presented as a congested, invaginated tubular structure and was deemed to comprise the left oviduct. After repositioning the oviductal prolapse, coelioscopy confirmed that the invaginated structure consisted of the anterior part of the left oviduct and incorporated a part of the ipsilateral mesovarium and mesosalpinx. A transplastron osteotomy was carried out to perform unilateral salpingectomy and bilateral ovariectomy. A definitive diagnosis of an oviductal leiomyoma was made based on histopathological and immunohistochemical examination of the invaginated part of the oviduct. In the present case, the authors highlight that neoplastic disorders should be considered as a cause of oviductal invagination and prolapse in chelonians. To the authors’ knowledge, this is the first report of the diagnosis and successful treatment of an oviductal leiomyoma in a Hermann’s tortoise.

Dynamics of proximal and distal transport of sodium in case of bilateral gonadectomy and the efficacy of hormonal replacement therapy

Introduction. The characteristic feature of current trauma in Ukraine and in the world is the prevalence of highly energetic skeletal trauma which is followed by the appearance of combined and multiple injuries with the formation of multiorgan dysfunction and failure. Because of the increase of life duration, the high interest of current traumatology is the investigation process of trauma course in older people. Among them the high interest is given to females in postmenopausal period. The decrease of estrogen level causes very unfavorable ground for the trauma course. However, the influence of severe trauma on changes in proximal and distal transport of sodium in case of hypoestrogenic state is not fully investigated. There is no available data concerning the effectiveness of hormonal replacement therapy in this condition.The goal of the study: is to investigate the influence of cranioskeletal injury on the dynamics of proximal and distal sodium transport in rats with bilateral ovariectomy in the period of late changes of traumatic disease and evaluate the effectiveness of hormonal replacement therapy. Materials and methods. Experiments were performed on 42 non-linear white female rats with the weight of 200-220 g. The model of hypoestrogenic state was performed via surgical removal of the ovaries. 1 month after the gonadectomy in rats skeletal trauma was performed. As a treatment option in one subgroup of rats with gonadectomy and cranioskeletal injury we performed hormonal replacement therapy. The control groups were formed by intact rats and osteoporotic rats 1 month after gonadectomy which were not injured. In control groups and after 1 and 2 months of posttraumatic period we were investigating the functional state of kidneys by performing the water upload method. Afterwards we performed the laboratory checkup of creatinine and sodium levels in serum and urine and additionally calculated the values of proximal and distal sodium transport. Results and its discussion. It was found that the level of proximal and distal sodium transport depends on the estrogen level, the decrease of its secretion leads to the decrease of sodium reabsorption in tubules and the increase in secretion. These changes were more prevalent in proximal tubules. In the course of trauma 1 month after posttraumatic period the value was decreasing in both research groups. However, in rats with gonadectomy the changes were much bigger and stayed at the same level until the 2nd month of the experiment. In rats without gonadectomy these values were achieving the same levels as control group until 2nd month. The use of combined hormonal replacement therapy caused the increase of proximal and distal sodium transport in comparison to the group without receiving treatment. The results that we got though was not achieving the level of rats without gonadectomy, but it showed the perspective for the use of combined hormonal replacement therapy in case of hypoestrogenic state for the decrease of renal dysfunction. Conclusions: Bilateral ovariectomy in female rats after 1 month shows the decrease of proximal and distal sodium levels comparing to rats with preserved gonads. The cranioskeletal injury that happened 1 month after bilateral ovariectomy causes the much bigger decrease of proximal and distal sodium transport comparing to rats with preserved gonads. The use of combined hormonal replacement therapy caused lower changes in proximal and distal sodium transport comparing to rats without this treatment.

Jingui Shenqi Pills Regulate Bone-Fat Balance in Murine Ovariectomy-Induced Osteoporosis with Kidney Yang Deficiency

Jingui Shenqi Pills (JGSQP) have been a staple of traditional Chinese medicine for thousands of years, used primarily as a treatment for kidney yang deficiency (KYD). In vitro analyses of JGSQP revealed strong induction of osteogenic differentiation and inhibition of adipogenic differentiation in bone-marrow-derived mesenchymal stem/stromal cells. However, the mechanisms by which JGSQP regulate the bone-fat balance in murine ovariectomy-induced osteoporosis with KYD have not been reported. Materials and Methods. Two-month-old female C57BL/6 mice were divided randomly into three groups: those receiving a sham operation (Sham); those undergoing bilateral ovariectomy and selection of KYD syndrome (Model); and those subjected to both bilateral ovariectomy and KYD syndrome selection for 8 weeks, followed by JGSQP treatment for 4 weeks (JGSQP). In the Sham and Model groups, mice were given the same dose of distilled water orally for 4 weeks. Animals from all three groups were euthanised at the 12th week. Vertebral microarchitecture and histomorphology were examined by micro-CT and H&E staining, respectively. In addition, we examined the mRNA expression of Akt, Wnt10b, Osterix (Osx), Fndc5, PPARγ, and Fabp4, as well as the protein of AKT, phosphorylation-AKT (p-AKT), BMP2, COL1A1, and FNDC5. Results. JGSQP treatment improved bone microarchitecture and mitigated histomorphological damage relative to the Model group. The osteoblast number (Ob.N/BS) and area (Ob.S/BS) were increased, whereas adipocyte number (adipocyte/tissue area) and area (adipocyte area/tissue area) were decreased in the JGSQP group. JGSQP treatment reduced the mRNA expression of Akt and adipogenesis-related genes (Fndc5, PPARγ, and Fabp4) while promoting osteogenesis-related genes (Wnt10b and Osx) mRNA expression. Additionally, the expression of p-AKT, BMP2, and COL1A1 proteins was increased and FNDC5 protein expression was decreased after JGSQP treatment. Conclusions. JGSQP treatment reversed murine ovariectomy-induced osteoporosis with KYD by controlling bone-fat balance via AKT pathway.

Moody Mares—Is Ovariectomy a Solution?

Unwanted behaviour in mares is a commonly presenting problem to the veterinarian. This behaviour may range from the mare being uncooperative or aggressive when handled on the ground, kicking, bucking or rearing when ridden or being aggressive towards other horses. This purpose of the study was to evaluate whether bilateral ovariectomy in mares with unwanted behaviour improved the mare’s behaviour and/or rideability from the owner’s perspective. The mares were grouped and compared statistically based on their histological classification as having either “normal” or neoplastic ovaries. This study is a retrospective case series report of twenty-eight ovariectomized mares. A semi-quantitative value (1–10) pre- and post-ovariectomy for A) behaviour on ground/in stable and B) rideability was given, based on the owner’s observations. The horses were grouped based on their histopathologic diagnosis as “Normal ovaries” or “Neoplasia”. Following ovariectomy, rideability improved, with a score of ≥5 in 80% (8/10) of mares with normal ovaries and in 57% (8/14) of mares with ovarian neoplasm. A behavioural improvement of ≥5 was observed in 40% (4/10) of mares with normal ovaries, and in 43% (6/14) of mares with ovarian neoplasm. A significant difference was observed between the semi-quantitative value pre- and post-ovariectomy in both groups. No difference was observed in change in behaviour and rideability score between the group with normal ovaries and neoplastic ovaries. Mares with unwanted behaviour not obviously related to the oestrus cycle and to painful conditions may benefit from ovariectomy to alter their behaviour and rideability.