scholarly journals Therapeutic Potential of Metformin and Vitex Agnus-Castus In Alleviating Cardiac Damage Induced By Hyperandrogenism In Polycystic Ovary Female Rats

2017 ◽  
Keyword(s):  
Therapeutic Potential ◽  
Polycystic Ovary ◽  
Female Rats ◽  
Cardiac Damage ◽  
Agnus Castus

Dexrazoxane does not protect against doxorubicin-induced damage in young rats

2003 ◽  
Vol 285 (2) ◽  
pp. H499-H506 ◽  
Author(s):  
Stéphanie Héon ◽  
Martin Bernier ◽  
Nicolas Servant ◽  
Stevan Dostanic ◽  
Chunlei Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Weight Gain ◽  
Heme Oxygenase ◽  
Caspase 3 ◽  
Exercise Program ◽  
Female Rats ◽  
Male Rats ◽  
Heme Oxygenase 1 ◽  
Cardiac Damage

Doxorubicin (DOX), an anticancer drug, causes a dose-dependent cardiotoxicity. Some evidence suggests that female children have an increased risk for DOX-mediated cardiac damage. To determine whether the iron chelator dexrazoxane (DXR) could reduce DOX-induced cardiotoxicity in the young, we injected day 10 neonate female and male rat pups with a single dose of saline or DOX, DXR, or DXR + DOX (20:1). We followed body weight gain with growth, measured cardiac hypertrophy after a 2-wk swim exercise program, markers of apoptosis (Bcl-2, BAX, BNIP1, caspase 3 activation), oxidative stress (heme oxygenase 1, protein carbonyl levels), the chaperone protein clusterin, and the transcriptional activator early growth response gene-1 (Egr-1) in hearts of nonexercised and exercised rats on neonate day 38. All DOX-alone and DXR + DOX-treated rats showed decreased weight gain, with female rats affected earlier than male rats. DXR-alone, DOX-alone, and DXR + DOX-treated rats had an increased heart weight-to-body weight (heart wt/body wt) ratio after the exercise program with female rats showing the largest increase in heart wt/body wt. Drug-treated females also showed increased cardiac apoptosis, as measured by the increased expression of the proapoptotic proteins BAX and BNIP1 and the appearance of caspase 3 activation products, and oxidative stress, as measured by increased heme oxygenase 1 expression, and reduced Egr-1 and clusterin expression when compared with the similarly treated male rats. We conclude that DXR preinjection did not reduce DOX-induced noncardiac and cardiac damage and that young female rats were more susceptible to DXR and DOX toxicities than age-matched male rats.

Abstract P040: Role of 20-HETE in Elevated Blood Pressure in Hyperandrogenemic Female Rats, a Model of Polycystic Ovarian Syndrome

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Chetan N Patil ◽  
Carolina Dalmasso ◽  
Rodrigo O Maranon ◽  
Huimin Zhang ◽  
Richard J Roman ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Polycystic Ovary ◽  
Premenopausal Women ◽  
Female Rats ◽  
Elevated Blood Pressure ◽  
Female Rat ◽  
Elevated Blood ◽  
Reproductive Disorder ◽  
Consomic Strain

Polycystic ovary syndrome (PCOS) is the most common reproductive disorder in premenopausal women, is characterized by hyperandrogenemia, metabolic syndrome and inflammation. They also exhibit elevated blood pressure (BP) but may not be treated since they do not meet the criteria for hypertension (BP>130/90 mm Hg). We have characterized a female rat model of hyperandrogenemia (HAF) using dihydrotestosterone (DHT) that mimics many characteristics of women with PCOS. In the present study we tested the hypothesis that androgen-induced upregulation of the cytochrome P450 4A2 isoform (CYP4A2) and the formation of 20-hydroxyeicosatetraenoic acid (20-HETE) in renal microvasculature contributes to the elevated BP in HAF rats. Female rats of SS.5BN consomic strain (wild type) rats and CYP4A2-/- rats on this same background were implanted with DHT (7.5mg/90d) or placebo pellets (n=5-8/grp) beginning at 6 wks of age; pellets were changed every 85 d. At 14 wks of age, rats were implanted with radiotelemetry transmitters, and mean arterial pressure (MAP) was measured for 10 days. Endogenous 20-HETE levels were measured using LC-MS in renal microvessels isolated using an Evans Blue sieving technique. DHT-treated HAF-SS.5BN rats had significantly higher MAP compared to placebo-SS.5BN (128±6 vs. 104±1 mmHg, p<0.004). In contrast, HAF-CYP4A2-/- rats had no change in MAP compared to placebo-CYP4A2-/- controls (120±4 vs 118±3 mmHg, p=NS). Endogenous 20-HETE levels in renal microvessels of HAF-SS.5BN rats were significantly increased compared to Placebo-SS.5BN (2.27±0.91 vs. 0.32±0.037 pmol/mg, p<0.01). The 20-HETE levels were lower in CYP4A2-/- than SS.5BN but DHT in HAF-CYP4A2-/- had no effect on 20-HETE levels compared to Placebo- CYP4A2-/-. These results suggest that androgen-mediated upregulation of the expression of CYP4A2 and the production of 20-HETE in renal microvessels contribute to elevated BP in HAF rats. These data also suggest that methods to attenuate 20-HETE may provide a novel therapeutic to reduce BP in women with PCOS. Work supported by NIH RO1HL66072 and PO1HL51971.

Cardiac response to doxorubicin and dexrazoxane in intact and ovariectomized young female rats at rest and after swim training

2012 ◽  
Vol 302 (10) ◽  
pp. H2048-H2057 ◽  
Author(s):  
Annie Calvé ◽  
Rami Haddad ◽  
Sarah-Neiel Barama ◽  
Melissa Meilleur ◽  
Igal A. Sebag ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Adult Survivors ◽  
Young Female ◽  
Cardiac Response ◽  
Female Rats ◽  
Cancer Therapies ◽  
Sprague Dawley ◽  
Cardiac Damage ◽  
Ovx Rats ◽  
The Impact

The impact of cancer therapies on adult cardiac function is becoming a concern as more children survive their initial cancer. Cardiovascular disease is now a significant problem to adult survivors of childhood cancer. Specifically, doxorubicin (DOX) may be particularly harmful in young girls. The objective of this study was to characterize DOX damage and determine the ability of dexrazoxane (DEX) to reduce DOX-mediated cardiac damage in sedentary and swim-trained female rats. Female Sprague-Dawley rats were left intact or ovariectomized (OVX) at weaning then injected with DEX (60 mg/kg) before DOX (3 mg/kg), DOX alone, or PBS. Rats were separated into sedentary and swim cohorts. Body weight was reduced in DOX:DEX- but not PBS- or DOX-treated rats. Echocardiographic parameters were similar in sedentary rats. Swim training revealed greater concentric remodeling in DOX-treated rats and reduced fractional shortening in DOX:DEX-treated rats. Calsequestrin 2 was reduced with DOX and increased with DOX:DEX postswim. Sarco(endo)plasmic reticulum Ca2+-ATPase 2a was reduced and calsequestrin 2 reduced further by swim training only in intact rats. OVX rats were heavier and developed eccentric remodeling post-swim with DOX and eccentric hypertrophy with DOX:DEX. Changes in SERCA2a and calsequestrin 2 expression were not observed. Ovariectomized DOX- and DOX:DEX-treated rats stopped growing during swim training. DEX coinjection did not relieve DOX-mediated cardiotoxicity in intact or hormone-deficient rats. DOX-mediated reductions in growth, cardiac function, and expression of calcium homeostasis proteins were exacerbated by swim. DEX coadministration did not substantially relieve DOX-mediated cardiotoxicity in young female rats. Ovarian hormones reduce DOX-induced cardiotoxicity.

scholarly journals Androgen Receptor Blocker Improves the Cardiometabolic Profile in a Rat Model of Polycystic Ovary Syndrome, but at What Cost?

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A803-A804
Author(s):  
Jacob E Pruett ◽  
Steven Everman ◽  
Edgar David Torres Fernandez ◽  
Kacey Davenport ◽  
Damian G Romero ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
Female Rats ◽  
Chow Diet ◽  
Model Assessment ◽  
Androgen Excess ◽  
Ovary Syndrome ◽  
Glutamyl Transferase ◽  
Cardiometabolic Profile

Abstract Introduction: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. PCOS is characterized by androgen excess and ovulatory dysfunction high prevalence of cardiovascular risk factors such as increased blood pressure (BP), insulin resistance (IR), and obesity. We have demonstrated previously that exposing prepubertal female rats to dihydrotestosterone (DHT) leads to increase in food intake (FI), body weight (BW), BP, and IR. We tested the hypothesis that administration of the AR blocker bicalutamide (BICA) would decrease BP, IR, and obesity in PCOS model. As there are previous reports of severe hepatotoxicity with the AR blocker flutamide, we also examined BICA effects in the liver. Methods: Four-week old female Sprague Dawley rats implanted with DHT pellets (7.5mg/90 days) or placebo (PBO) were randomized to standard chow diet with or without the AR blocker bicalutamide (BICA) at a dose of 250 mg/kg/day throughout the study (n=10/group). BW and FI were measured weekly. BP and heart rate (HR) were measured by radiotelemetry. Fasting plasma was collected for IR (Homeostatic model assessment for IR, HOMA-IR). At euthanasia, the liver was collected, as well as plasma for gamma glutamyl transferase (GGT), alanine transaminase (ALT), and aspartate transaminase (AST) quantification. Results: PCOS rats had increased BW, FI, IR, and BP compared to PBO. BICA treatment had no impact on BW (285.3 ± 7.0 vs 270 ± 8.2 g, P=0.2) as well as FI and HR in PCOS. However, in PCOS, BICA decreased HOMA-IR (5.10 ± 0.40 vs 3.33 ± 0.31, P&lt;0.05) and BP (115.4 ± 0.7 vs 105.3 ± 0.2 mmHg, P&lt;0.01). Compared to PBO, PCOS+BICA rats had similar IR (3.83 ± 0.28 vs 3.33 ± 0.31, P=0.7) and BP (107.4 ± 0.8 vs 105.3 ± 0.2 mmHg, P=0.9). In addition, the liver weight to tibia length ratio was drastically increased by BICA in PCOS (222.9 ± 9.5 vs 360.4 ± 16.9 mg/mm, P&lt;0.0001) as well as GGT (0.88 ± 0.88 vs 11.67 ± 0.58 U/L, P&lt;0.0001), though it decreased AST (60.2 ± 6.9 vs 42.4 ± 1.9 U/L, P&lt;0.05) and had no impact on ALT. Conclusion: In summary, in a model of PCOS, BICA treatment abolished IR and BP, independent of FI, BW and HR. Prompt treatment with an AR blocker can normalize increased IR and BP triggered by androgen excess in females. Further studies need to be done to fully understand the effect of BICA in the liver in PCOS. The beneficial effect of AR blockers as a therapeutic option to improve the cardiometabolic profile in PCOS may be hampered by its liver toxicity.

Intense electroacupuncture normalizes insulin sensitivity, increases muscle GLUT4 content, and improves lipid profile in a rat model of polycystic ovary syndrome

2010 ◽  
Vol 299 (4) ◽  
pp. E551-E559 ◽  
Author(s):  
Julia Johansson ◽  
Yi Feng ◽  
Ruijin Shao ◽  
Malin Lönn ◽  
Håkan Billig ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Polycystic Ovary Syndrome ◽  
Lipid Profile ◽  
Muscle Protein ◽  
Polycystic Ovary ◽  
Low Frequency ◽  
Density Lipoprotein ◽  
Female Rats ◽  
Ovary Syndrome

Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and insulin resistance, possibly reflecting defects in skeletal muscle and adipocyte insulin signaling. Low-frequency (2 Hz) electroacupuncture (EA) increases insulin sensitivity in female rats with dihydrotestosterone (DHT)-induced PCOS, but the mechanism is unclear. We hypothesized that low-frequency EA regulates mediators involved in skeletal muscle glucose uptake and metabolism and alters the lipid profile in rats with DHT-induced PCOS. To test this hypothesis, we implanted in prepubescent female rats 90-day continuous-release pellets containing DHT (PCOS). At 70 days of age, the rats were randomly subdivided into two groups: one received low-frequency EA (evoking muscle twitches) for 20–25 min five times/wk for 4–5 wk; the other did not. Controls were implanted with pellets containing vehicle only. All three groups were otherwise handled similarly. Lipid profile was measured in fasting blood samples. Insulin sensitivity was determined by euglycemic hyperinsulinemic clamp, soleus muscle protein expression of glucose transporter 4 (GLUT4), and phosphorylated and nonphosphorylated Akt, and Akt substrate of 160 kDa was determined by Western blot analysis and GLUT4 location by immunofluorescence staining. PCOS EA rats had normalized insulin sensitivity, lower levels of total high-density lipoprotein and low-density lipoprotein cholesterol, and increased expression of GLUT4 in different compartments of skeletal muscle compared with PCOS rats. Total weight and body composition did not differ in the groups. Thus, in rats with DHT-induced PCOS, low-frequency EA has systemic and local effects involving intracellular signaling pathways in muscle that may, at least in part, account for the marked improved insulin sensitivity.

Determine Cyp17a1 and Ki67 Expressions in Pcos Induced Rat Model Treated with Sepia pharaonis Ink Extract Proves Effective

2020 ◽  
Author(s):  
J. Leonoline Ebenezer ◽  
R. Gunapriya ◽  
K. Ranganathan ◽  
R. Vijayaraghavan ◽  
M. Karthik Ganesh
Keyword(s):  
Rat Model ◽  
Polycystic Ovary ◽  
Clomiphene Citrate ◽  
Drug Effects ◽  
Female Rats ◽  
Therapeutic Drug ◽  
Control Group ◽  
Vaginal Smears ◽  
Sepia Pharaonis ◽  
Pcos Group

Background: The present study aims to evaluate the therapeutic action of Sepia pharaonis ink extract in experimentally induced polycystic ovary syndrome (PCOS) rat model and perform Immunohistochemistry to confirm the findings.Methods: The female rats were grouped into 5 consisting of six animals each. Only water was given to the control group. For inducing PCOS, Letrozole 1mg/kg.b.wt was administered to the subsequent four groups for 21 days. To the third group, an allopathic drug, clomiphene citrate 1mg/kg was given for 19 days after PCOS induction. The SPIE was subjected to lyophilisation to make a black powder and next two groups were administered orally with two different dosages of SPIE (100mg and 200mg respectively) mixed with water after PCOS induction. Vaginal smears were taken from all groups till 21 days and then treatment was started with clomiphene citrate (CC) and SPIE. After 21 days, vaginal smears were taken from all groups till ovulation was induced. The test drug effects were studied using ovary weight both right and left, body weight, hormonal levels, histopathology of ovary and Immunohistochemistry. Result: PCOS group showed rapid increase in the ovarian weight when compared to control and was reduced by CC and SPIE treatment. The levels of progesterone and estradiol were found lower and testosterone levels were found higher in PCOS rats which were favourably altered. Vaginal smears coincided with the histopathology and immunohistochemistry findings. SPIE can be used as a therapeutic drug for PCOS in future, reduce infertility complaint of females and prevent early inception of diabetes mellitus.

scholarly journals The Clinical and Biological Effects of Homeopathically Prepared Signaling Molecules: A Scoping Review

Homeopathy ◽  
2021 ◽  
Author(s):  
Raj Kumar Manchanda ◽  
Meeta Gupta ◽  
Ankit Gupta ◽  
Robbert van Haselen
Keyword(s):  
Scoping Review ◽  
Clinical Studies ◽  
English Language ◽  
Therapeutic Potential ◽  
Polycystic Ovary ◽  
Biological Effects ◽  
Signaling Molecules ◽  
Respiratory Allergies ◽  
Wide Range ◽  
External Stimuli

Abstract Background Signaling molecules such as cytokines and interleukins are key mediators for the immune response in responding to internal or external stimuli. Homeopathically prepared signaling molecules have been used therapeutically for about five decades. However, these types of products are not available in many countries and their usage by homoeopaths is also infrequent. The aim of this scoping review is to map the available pre-clinical and clinical data related to the therapeutic use of homeopathically prepared signaling molecules. Methods We conducted a scoping review of clinical and pre-clinical studies of therapeutically used signaling molecules that have been prepared in accordance with an officially recognized homeopathic pharmacopoeia. Articles in peer-reviewed journals reporting original clinical or pre-clinical research of homeopathically prepared signaling molecules such as interleukins, cytokines, antibodies, growth factors, neuropeptides and hormones, were eligible. Non-English language papers were excluded, unless we were able to obtain an English translation. An appraisal of eligible studies took place by rating the direction of the outcomes on a five-point scale. The quality of the papers was not systematically assessed. Results Twenty-eight eligible papers, reporting findings for four different manufacturers' products, were identified and reviewed. Seventeen papers reported pre-clinical studies, and 11 reported clinical studies (six experimental, five observational). A wide range of signaling molecules, as well as normal T-cell expressed specific nucleic acids, were used. A majority of the products (21 of 28) contained two or more signaling molecules. The most common clinical indications were psoriasis, vitiligo, rheumatoid arthritis, respiratory allergies, polycystic ovary syndrome, and herpes. The direction of the outcomes was positive in 26 papers and unclear in two papers. Conclusion This scoping review found that there is a body of evidence on the use of homeopathically prepared signaling molecules. From a homeopathy perspective, these substances appear to have therapeutic potential. Further steps to explore this potential are warranted.

scholarly journals Effect of Vitex Agnus-Castus Ethanolic Extract on Sex Hormones in Streptozotocin-Induced Diabetic Rats

2020 ◽  
Author(s):  
Fatemeh Soleymanzadeh ◽  
Minoo Mahmoodi ◽  
Siamak Shahidi
Keyword(s):  
Sex Hormones ◽  
Experimental Studies ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Female Rats ◽  
Control Group ◽  
Diabetic Patients ◽  
High Dose ◽  
Fruit Extract ◽  
Agnus Castus

Objective: Diabetes mellitus is recognized as one of the serious global health problems. There are evidences regarding the high prevalence of sexual dysfunction in diabetic patients. Experimental studies revealed a positive effect of Vitex agnus-castus (Vitex), on sexual function and behaviors. In this research, the effect of Vitex on sexual hormones in streptozotocin-(STZ) induced diabetic rats was investigated. Materials and methods: A Thirty adult female Wistar rats were divided into five groups. 1-control group (non-diabetic), 2- diabetic group (received normal saline) and three induced diabetic groups treated with different doses (400, 200 and 100 mg/kg) of Vitex. Treatment groups received Vitex fruit extract by gavage for 7 days. The levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone and estrogen in serum were measured. Results: Levels of LH, FSH, estrogen and progesterone and average body weight was lower in diabetic group compared to control group (p <0.010). Animals received high dose of Vitex fruit extract (400mg/kg) had significantly higher levels of serum LH, FSH, estrogen and progesterone compared to diabetic group (p < 0.010). In animals receiving minimum dose (100mg/kg) of Vitex, no difference was observed compared to diabetic group (p > 0.010). Conclusion: It can be concluded that Vitex fruit extract probably has regulatory effect on diabetes-induced change in the levels of sex hormones in female rats. Vitex fruit extract can improve serum levels of sex hormones in an animal model of STZ-induced diabetes.

scholarly journals Vitex agnus castus and Some Female Disorders: A Review

2021 ◽  
Author(s):  
Muna O. Alamoudi ◽  
Yousef F. Bakrshoom
Keyword(s):  
Polycystic Ovary ◽  
Potential Effect ◽  
Arab Countries ◽  
Deciduous Tree ◽  
Beneficial Effects ◽  
Natural Medicine ◽  
The People ◽  
Agnus Castus ◽  
Fat Liver ◽  
Dopaminergic Antagonists

Vitex agnus castus L., is a deciduous tree which has been utilized in ancient Greece, Iran, Egypt and Rome for over 2500 years for a large variety of female reproductive system health difficulties. In Saudi Arabia, many women have menstrual cycle disturbances and menopausal dysfunction and many have polycystic ovary syndrome at young age. Using Vitex is not in Saudi tradition like other Arab countries. Recently, just few people used this herb for treating some infertility problems. A variety of beneficial effects of this curative herb have been reported in clinical studies, including antioxidant, anti-inflammatory, hypolipidemic, anti-diabetic, hormonal modulatory, anti-nociceptive and opioidergic activities, preventing oxidative stress and nonalcoholic fat liver disease. Adverse effects of the plant are mild and reversible. The advantages of this herb as natural medicine attract the people and make it one of best choose and utilize widely in women disorders specially that related with menopauses. Its constituents could interact with dopaminergic antagonists and exhibited progesteronic and estrogenic activities. This brief review introduces this plant to Saudi society and others to expand it usage and discusses the potential effect of the plant to cure some of the women disorders displaying its main ingredients and the side effects.

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