scholarly journals THE INVESTIGATION OF PHARMACOLOGICAL PROPERTIES OF VAGINAL GEL WITH RESVERATROL AND HYALURONIC ACID IN CONDITIONS OF EXPERIMENTAL HYPOESTROGENIC STATE IN RATS

2021 ◽  
Vol 17 (1) ◽  
pp. 74-82
Author(s):  
O.A. Stryha ◽  
G.V. Zaychenko ◽  
S.I. Savosko ◽  
K.Y. Sorokopud

Relevance. The menopausal period due to irreversible loss of ovarian function is accompanied by various clinical symptoms and systemic changes. In turn, hormone replacement therapy has a number of contraindications and side effects, so now there is a need to find and create prophylactic and therapeutic agents based on natural compounds that are related to β-estrogen receptors. Vaginal gel with resveratrol and hyaluronic acid can reduce atrophic manifestations of the vaginal mucosa and affect various symptoms of menopause. However, the nature of the effect, dosage, and consequences of long-term use of resveratrol need further study. Objective: to study pharmacological properties of a new vaginal gel with resveratrol and hyaluronic acid (HA) in a model of hypoestrogenism in ovariectomized rats. Materials and methods. The experiments were performed on 24 outbred white nonlinear female rats, which were divided into 4 groups: intact control, controlled pathology, controlled pathology, and administration of resveratrol with hyaluronic acid, controlled pathology, and administration of a comparison drug with synthetic estrogen. The effectiveness of the drugs was assessed by their effect on the blood levels of the sex hormones estrogen and progesterone, on body weight, on body temperature, on the pH of vaginal secretions, on the state of the vaginal mucosa. Results. 28-day vaginal injection of gel with resveratrol and hyaluronic acid slowed down and normalized weight gain of ovariectomized female rats, stabilized skin temperature and induced normalization of the pH of vaginal secretions of the vagina, normalized the level of sex hormones in the blood, promoted the restoration of the epithelial plate of the vagina. Conclusions. The results showed the feasibility of developing and using a new vaginal gel with resveratrol as an alternative to hormone-containing drugs for the prevention or treatment of pathological hypoestrogenic conditions arising from estrogen deficiency.

2008 ◽  
Vol 67 (1) ◽  
pp. 19-27 ◽  
Author(s):  
Caroline E. Childs ◽  
Meritxell Romeu-Nadal ◽  
Graham C. Burdge ◽  
Philip C. Calder

Dietary n-3 PUFA have many beneficial effects on cell and tissue function and on human health. In mammals the n-3 essential fatty acid α-linolenic acid (ALNA) can be converted into longer-chain (LC) n-3 PUFA such as EPA and DHA via a series of desaturase and elongase enzymes that are mainly active in the liver. Human studies have identified that males and females appear to differ in their ability to synthesise EPA and DHA from ALNA, with associated differences in circulating concentrations. Based on studies of women using the contraceptive pill or hormone-replacement therapy and of trans-sexual subjects it is suggested that sex hormones play a role in these differences. The rat has been used to investigate gender differences in n-3 PUFA status since this model allows greater dietary control than is possible in human subjects. Like human subjects, female rats have higher plasma DHA concentrations than males. Rats also respond to increased dietary ALNA in a way that is comparable with available human data. The concentrations of LC n-3 PUFA in rat plasma and tissues are positively associated with circulating concentrations of oestradiol and progesterone and negatively associated with circulating concentrations of testosterone. These findings suggest that sex hormones act to modify plasma and tissue n-3 PUFA content, possibly by altering the expression of desaturase and elongase enzymes in the liver, which is currently under investigation.


2008 ◽  
Vol 33 (6) ◽  
pp. 1207-1212 ◽  
Author(s):  
Sobia Iqbal ◽  
Amy Thomas ◽  
Kareem Bunyan ◽  
Peter M. Tiidus

Limited research has been conducted on the effects of progesterone alone, or in combination with estrogen, on leukocyte infiltration in skeletal muscle following exercise. To investigate the effects of these female sex hormones, ovariectomized female rats were divided into 4 exercise and 4 control groups: sham, estrogen, progesterone, and a combination of estrogen plus progesterone. Following 8 days of hormone replacement and 24 h postexercise, soleus (red) and superficial (white) vastus muscles were removed and immunostained for His48 (neutrophil)- and ED1 (macrophage)-positive cells. The postexercise increase in leukocyte infiltration was completely (p < 0.05) attenuated with estrogen supplementation alone in both muscle types, relative to sham. Progesterone treatment alone also resulted in a smaller (20%–30%) but significant (p < 0.05) attenuation of postexercise muscle leukocyte infiltration. The combination of estrogen and progesterone treatment did not significantly alter the attenuation seen with estrogen supplementation alone. Hence, progesterone can independently attenuate postexercise muscle leukocyte infiltration, albeit to a lesser degree than estrogen, and it will not negate or accentuate the effect of estrogen.


2017 ◽  
Vol 20 (3) ◽  
Author(s):  
Luana Marotta Reis Vasconcellos ◽  
Vanessa Ávila Sarmento Silveira ◽  
Raphaela Silveira Medeiros ◽  
Márian Yaktin Amorin ◽  
Yasmin Rodarte Carvalho ◽  
...  

<p><strong>Objective</strong>: A decrease in granular convoluted tubule (GCT) cells and acini occurs in the submandibular glands of castrated female rats, while in rats submitted to hormone replacement and phytotherapy with soy isoflavones, this effect is reversed. This study aimed to elucidate the mechanisms through which these changes occur. <strong>Material and Methods</strong>: Rats (n=84) were ovariectomized and 21 were sham-operated. Ovariectomized rats were randomly subdivided and orally administered the following: 17 β-estradiol (OVX-E; n=21), 15 mg/kg/day of soy isoflavone extract (OVX-I; n=21), 17 β-estradiol + soy isoflavone extract (OVX-A; n=21); and water as placebo (OVX; n=21). The rats were euthanized three, five and eight weeks after ovariectomy. The submandibular salivary glands were submitted to histological processing with HE stain and immunohistochemistry was performed using the streptavidin-biotin-peroxidase complex. The cell area and the expression of proliferating cell nuclear antigen and estrogen receptor β were evaluated. <strong>Results</strong>: The results were statistically analyzed by ANOVA and Tukey test. A decrease in the area of GCT cells in the OVX, was observed, in contrast with an increase in the OVX-E. PCNA in the acinar cells and estrogen receptors were elevated in the OVX-I group. <strong>Conclusion</strong>: Castration exerts an immediate reductive effect on the volume of GCT cells. Estrogens, soy isoflavones and their combination have different mechanisms of action on the homeostasis of the gland. Estrogens cause an increase in GCT cells area, while isoflavones enhance cell proliferation and the expression of estrogen receptor-β. Their association showed no additional increase in the effect studied.</p><p><strong>Keywords</strong></p><p>Estrogen; Morphometry; Salivary glands; Soy isoflavones.</p>


Gels ◽  
2021 ◽  
Vol 7 (4) ◽  
pp. 157
Author(s):  
Guglielmo Stabile ◽  
Giuseppe Ricci ◽  
Maria Sole Scalia ◽  
Francesco De Seta

An experimental model of dryness on vaginal mucosa is proposed to assess the efficacy of a new vaginal gel (Respecta® Hydragel Ref 17031). The dryness model was induced on reconstituted human vaginal epithelium (HVE) by incubating the tissues in modified environmental conditions (R.H. < 50% and T = 40 °C) for 48 h. The products were applied on the ‘Dry’ HVE models for 24 h (series 48 h + 24 h) in standard culture conditions (37 °C 5% CO2). Their efficacy in counteracting vaginal dryness was assessed and compared to tissues treated with saline solution and cultured in standard culture conditions (negative control) and to untreated tissues incubated in dryness conditions for 48 h and then recovered after 24 h in standard culture conditions (positive control). The products’ efficacy was quantified by measuring the following parameters: (1) water flux and direct moisturization by AQP3 immunohistochemical staining, and (2) maintenance of moisturization and elasticity of the mucosa by hyaluronic acid (CD44) immunofluorescence staining. Respecta® Hydragel demonstrated efficacy in regulating the water flux by inducing AQP3 expression thus determining a positive water balance within the vaginal epithelium. It induced a remodelling of the epithelium morphology with restored trophism compared to the dry HVE control. Furthermore, it demonstrated a significant increase of the expression of CD44, related to hyaluronic acid (HA) distribution in the extracellular matrix. HA has the ability to act on the cellular matrix composition and its renewal compared to the dry HVE control. Through these mechanisms it induces a deep hydration and elasticity of the vaginal mucosa.


Endocrinology ◽  
2005 ◽  
Vol 146 (1) ◽  
pp. 287-293 ◽  
Author(s):  
Neil J. MacLusky ◽  
Victoria N. Luine ◽  
Tibor Hajszan ◽  
Csaba Leranth

Previous studies have demonstrated that estradiol-17β and estradiol-17α both induce short-latency effects on spatial memory in rats, estradiol-17α being at least as potent as its 17β isomer. To determine whether the mechanisms underlying these behavioral responses might include effects on hippocampal synaptic plasticity, CA1 pyramidal spine synapse density (PSSD) was measured in ovariectomized rats within the first few hours after sc estrogen injection. PSSD increased markedly (by 24%) 4.5 h after the administration of 45 μg/kg estradiol-17β. The PSSD response was significantly greater (44% above control) 30 min after estradiol-17β injection and was markedly dose dependent; a 3-fold lower estradiol-17β dose (15 μg/kg) did not significantly affect CA1 PSSD at either 30 min or 4.5 h. Estradiol-17α was a more potent inducer of PSSD than estradiol-17β. Dose-response analysis determined an ED50 for the effect of estradiol-17α on PSSD of 8.92 ± 1.99 μg/kg, with a maximal response at 15 μg/kg. These results demonstrate that high doses of estradiol induce rapid changes in CA1 PSSD. CA1 spine synapse formation appears to be more sensitive to estradiol-17α than to estradiol-17β, paralleling previous data on the effects of these two steroids on spatial memory. Rapid remodeling of hippocampal synaptic connections may thus contribute to the enhancement of spatial mnemonic processing observed within the first few hours after estrogen treatment. The potency of estradiol-17α suggests that hormone replacement therapy using this steroid might be useful clinically in ameliorating the impact of low endogenous estrogen production on the development and progression of neurodegenerative disorders involving the hippocampus.


2021 ◽  
pp. 92-100
Author(s):  
A.A. Sukhanova ◽  
V.V. Sumenko ◽  
R.R. Tkachuk

Research objective: to evaluate the clinical efficacy of vaginal gel with hyaluronic acid Revitaxa gel in comparison with synthetic estrogen-like topical agent in the treatment of women with genitourinary syndrome, to determine the recurrence rate of atrophic changes as a result of these schemes.Materials and methods. The study included 60 women with genitourinary manifestations and atrophic changes of the vaginal mucosa and cervical epithelium. Clinical, cytological and colposcopic studies were performed to analyze the vaginal epithelium, vaginal microbiocenosis and vaginal tissues. All women with an inflammatory type of smear were prescribed vaginal rehabilitation before the study. Repeated laboratory examination after anti-inflammatory, antibacterial topical therapy confirmed no pathogenic microflora, but signs of atrophy persisted in all women. All women are prescribed local treatment to improve the reparative processes of the vaginal mucosa. The main group (30 women) used Revitaxa gel for local therapy; the control group (30 women) used vaginal suppositories with the synthetic estrogen-like agent promestrienum.Results. Cytological remission after treatment was observed in all women of the control group and in 76.7% of patients in the main group. Restoration of the vaginal mucosa was detected in all patients of the control group and in 90% of patients in the main group. Repeated examinations 4 months after the end of therapy determined no recurrence of atrophic colpitis in 53.3% of patients in the main group and in 30% of women in the control group. Preservation of a favorable estatrophic type of smears was observed in 43.3% of women of group I and 13.3% of patients of group II (p <0.05), which indicates a more stable effect of hyaluronic acid compared with estrogen-like agent.Conclusions. Vaginal gel with hyaluronic acid Revitaxa gel in women with genitourinary syndrome gives results similar to the synthetic estrogen-like drug with promestrienum for topical treatment according to colposcopy, cytology, hormonal colpocytology and clinical indicators. Therefore, Revitaxa gel may be recommended for effective use in women with atrophic colpitis who refuse or have contraindications for topical hormonal agents.


2014 ◽  
Vol 31 (3) ◽  
pp. 208-213 ◽  
Author(s):  
Shuai-Bin Liu ◽  
Shao-Li Liu ◽  
Xiao-Ling Gan ◽  
Qin Zhou ◽  
Li-Na Hu

2015 ◽  
Vol 2;18 (2;3) ◽  
pp. 195-205
Author(s):  
Wen Wang

Hormone replacement remains one of the common therapies for menopause-related pain but is associated with risk of orofacial or back pain. Spinal endomorphin-2 (EM-2) is involved in varied pain and its release is steroid-dependent, but whether increasing spinal EM-2 can inhibit thermal hyperalgesia and inflammatory pain in ovariectomized (OVX) female rats, an animal model mimicking menopause, is not clear, nor is the potential involvement of spinal mu-opioid receptor (MOR). In the current study, we revealed that the temporal decrease of spinal EM-2 is accompanied with OVX-induced thermal hyperalgesia that was dose-dependently attenuated by intrathecal (IT) delivery of EM2. The subcutaneous injection of formalin-induced inflammatory pain in OVX rats was exacerbated and IT delivery of EM-2 dose-dependently inhibited the inflammatory pain. However, the ED50 for IT delivery of EM-2 on thermal hyperalgesia is smaller than that on inflammatory pain in OVX rats, suggesting different contributions of the EM-2 system to these 2 pain modalities in OVX rats. IT pretreatment with MOR antagonist, betafunaltrexamine (β-FNA), attenuated IT EM-2 analgesia on both thermal hyperalgesia and inflammatory pain in OVX rats. Furthermore, IT delivery of EM-2 did not affect the animals’ locomotion or anxiety status. Our findings suggested that IT EM-2 might be a safer analgesia strategy than hormone replacement therapy in reducing risk of orofacial or back pain. However, a long-lasting form of EM-2 with less tolerance is needed to induce sustained analgesia. Key words: analgesia, intrathecal, endomorphin, ovariectomize, rat


Scientifica ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Fatemeh Eshraghi-Jazi ◽  
Ardeshir Talebi ◽  
Fatemeh Sadat Mirsaeedi ◽  
Sarina Ahmadian ◽  
Fatemeh Moslemi ◽  
...  

Background. Gentamicin (GM) induced nephrotoxicity may be sex hormones related. The effects of sex hormones on GM induced nephrotoxicity in gonadectomized rats were investigated.Methods. Ovariectomized rats received 0.25, 0.5, or 1 mg/kg/week of estradiol (ES) alone or accompanied with 10 mg/kg/week of progesterone (Pro) for two weeks followed by GM (100 mg/kg/day) for 9 days. Castrated rats were also treated with 10, 50, or 100 mg/kg/week of testosterone (TS) for two weeks and then received GM. In addition, a single castrated group received 0.25 mg/kg/week of ES plus GM.Results. GM increased the serum levels of blood urea nitrogen (BUN) and creatinine (Cr) and kidney tissue damage score (KTDS) (P<0.05). TS had no effect on the serum levels of BUN and Cr and KTDS, while low dose of ES intensified these parameters in male (P<0.05). ES (0.5 mg/kg) without Pro ameliorated KTDS in female (P<0.05) while ES (1 mg/kg) with or without Pro exacerbated the BUN values and Cr values, KTDS, and body weight loss (P<0.05).Conclusion. ES (0.5 mg/kg) without Pro ameliorated kidney damage induced by GM in female while neither TS nor ES had beneficial effect on nephrotoxicity induced by GM in male, although ES aggravated it.


1998 ◽  
Vol 66 (1) ◽  
pp. 322-329 ◽  
Author(s):  
Julie B. Livingston ◽  
Shan Lu ◽  
Harriet Robinson ◽  
Deborah J. Anderson

ABSTRACT Vaccines are being sought for contraception and the prevention of sexually transmitted diseases. However, progress is slow in this area largely because of lack of information on induction of protective immune responses in genital tract mucosa. In this study, we investigated whether in vivo transfection with a model DNA-based antigen delivered by gene gun technology would induce an antibody response detectable in vaginal secretions. Female rats were immunized with plasmids encoding human growth hormone (HGH) under the control of a cytomegalovirus promoter (pCMV/HGH) via vaginal mucosa (V), Peyer’s patch (PP), and/or abdominal skin (S) routes. Localization of HGH in the target tissues demonstrated that all three sites can be transfected in vivo with pCMV/HGH. Vaginal tissues expressed roughly the same level of plasmid as skin. Antibodies to HGH were detectable in serum and vaginal secretions in rats immunized with pCMV/HGH. In the rats primed and boosted vaginally, vaginal immunoglobulin A (IgA) and IgG antibody titers to HGH were sustained for at least 14 weeks, whereas rats immunized via other routes and protocols (S/V, S/S, PP/PP, or PP/V) did not consistently sustain significant vaginal antibody titers beyond week 6. DNA-based immunizations administered by the gene gun may be an effective method of inducing local immunity in the female genital tract.


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