High Fat Diet Exaggerate Metabolic and Reproductive PCOS Features by Promoting Oxidative Stress: An Improved EV Model in Rats.

Background and Objectives: Polycystic ovary syndrome (PCOS) is a frequent multifactorial endocrinopathy affecting women in the reproductive period, often associated with infertility and metabolic disorders. The use of animal models helps to better understand etiopathogenesis, enabling the examination of the effects of certain drugs in order to discover the best possible therapeutic approach. We tried to investigate the additional effect of estradiol-valerate (EV) and high-fat diet (HFD) in female rats to explore PCOS-related alterations with special focus on oxidative stress. Materials and Methods: Animals were divided into three groups: control group (CTRL, n = 6), estradiol-valerate group (EV, n = 6), and estradiol-valerate group on HFD (EV + HFD, n = 6). PCOS was induced by single subcutaneous injection of long-acting EV in a dose of 4 mg/per rat. We tried to improve the metabolic characteristics of the PCOS animal model by adding HFD, so the CTRL and EV group had a regular diet, while the EV + HFD group had HFD during the induction period of 60 days. Results: We observed alterations of anthropometric parameters and hormonal disturbances, along with estrus cycle impairment reassembly to obese-type PCOS phenotype. Moreover, glucose metabolism was impaired after addition of HFD to EV protocol, contrary to EV administered alone. Histological analysis confirmed more numerous cystic follicles after the combination of EV and HFD protocol. The alterations of oxidative stress markers could be related to and serve as the mechanistic base for development of PCOS-related endocrine, reproductive, and metabolic properties. Conclusions: The additive effect of EV and HFD was obvious in the majority of the parameters observed. Our study strongly demonstrated metabolic as well as reproductive properties of PCOS in rats.

SGLT2 inhibitors: a focus on cardiac benefits and potential mechanisms.

This paper highlights the cardioprotective potential of sodium-glucose cotransporter 2 inhibitors (SLGT2i), as well as several most discussed mechanisms responsible for their cardioprotection. Cardiovascular diseases are considered a primary cause of death in nearly 80% of type 2 diabetes mellitus (T2DM) patients, with a 2-4-fold greater incidence of heart failure (HF) among diabetics. As novel hypoglycemics, SGLT2i showed exceptional cardiovascular benefits, reflected through robust reductions of cardiovascular mortality and hospitalization for HF in T2DM patients. Recently, those effects have been reported even in patients with HF and reduced ejection fraction irrespectively of diabetic status, suggesting that cardioprotective effects of SGLT2i are driven independently of their hypoglycemic actions. SGLT2i exerted hemodynamic and metabolic effects, partially driven by natriuresis and osmotic diuresis. However, those systemic effects are modest, and therefore cannot be completely related to the cardiac benefits of these agents in T2DM patients. Hence, increased circulating ketone levels during SGLT2i administration have brought out another hypothesis of a cardiac metabolic switch. Moreover, SGLT2i influence ion homeostasis and exert anti-inflammatory and antifibrotic effects. Their enviable influence on oxidative stress markers, as well as anti- and pro-apoptotic factors, have also been reported. However, since the main mechanistical contributor of their cardioprotection has not been elucidated yet, a joint action of systemic and molecular mechanisms has been suggested. In the light of ongoing trials evaluating the effects of SGLT2i in patients with HF and preserved ejection fraction, a new chapter of beneficial SGLT2i mechanisms is expected, which might resolve their main underlying action.

Dose-dependent effects of perfluorocarbon-based blood substitute on cardiac function in myocardial ischemia-reperfusion injury.

The main goal of this study was to investigate the cardioprotective properties in terms of effects on cardiodynamics of perfluorocarbon emulsion (PFE) in ex vivo-induced ischemia-reperfusion injury of an isolated rat heart. The first part of the study aimed to determine the dose of 10% perfluoroemulsion (PFE) that would show the best cardioprotective effect in rats on ex vivo-induced ischemia-reperfusion injury of an isolated rat heart. Depending on whether the animals received saline or PFE, the animals were divided into a control or experimental group. They were also grouped depending on the applied dose (8, 12, 16 ml/kg body weight) of saline or PFE. We observed the huge changes in almost all parameters in the PFE groups in comparison with IR group without any pre-treatment. Calculated in percent, dp/dt max was the most changed parameter in group treated with 8 mg/kg, while the dp/dt min, SLVP, DLVP, HR, and CF were the most changed in group treated with 16 mg/kg 10 h before ischemia. The effects of 10% PFE are more pronounced if there is a longer period of time from application to ischemia, i.e., immediate application of PFE before ischemia (1 h) gave the weakest effects on the change of cardiodynamics of isolated rat heart. Therefore, the future of PFE use is in new indications and application methods, and PFE can also be referred to as antihypoxic and antiischemic blood substitute with mild membranotropic effects.

Guanidinoacetic acid provides superior cardioprotection to its combined use with betaine and (or) creatine in HIIT-trained rats.

This study aimed to determine how guanidinoacetic acid (GAA) or its combined administration with betaine (B) or creatine (C) influences the cardiac function, morphometric parameters, and redox status of rats subjected to high-intensity interval training (HIIT). This research was conducted on male Wistar albino rats exposed to HIIT for 4 weeks. The animals were randomly divided into five groups: HIIT, HIIT + GAA, HIIT + GAA + C, HIIT + GAA + B, and HIIT + GAA + C + B. After completing the training protocol, GAA (300 mg/kg), C (280 mg/kg), and B (300 mg/kg) were applied daily per os for 4 weeks. GAA supplementation in combination with HIIT significantly decreased the level of both systemic and cardiac prooxidants ( O 2 - , H2O2, NO 2 - , and thiobarbituric acid reactive substances) compared with nontreated HIIT (p < 0.05). Also, GAA treatment led to an increase in glutathione and superoxide dismutase levels. None of the treatment regimens altered cardiac function. A larger degree of cardiomyocyte hypertrophy was observed in the HIIT + GAA group, which was reflected through an increase of the cross-sectional area of 27% (p < 0.05) and that of the left ventricle wall thickness of 27% (p < 0.05). Since we showed that GAA in combination with HIIT may ameliorate oxidative stress and does not alter cardiac function, the present study is a basis for future research exploring the mechanisms of cardioprotection induced by this supplement in an HIIT scenario.

The Evaluation of Healing Properties of Galium verum-Based Oral Gel in Aphthous Stomatitis in Rats.

Although oral ulcers represent one of the most frequent oral mucosal diseases, the available treatment is not sufficient to provide complete ulcer recovery without side-effects. Therefore, the aim of our study was to prepare a mucoadhesive oral gel based on Galium verum ethanol extract (GVL gel) and reveal its healing effects in the model of aphthous stomatitis in rats. Rats with oral ulcers were divided into the following groups: control (untreated), gel base (ulcer was treated with the gel base, three times per day for 10 days), and GVL gel group (the ulcer was treated with GVL gel in the same way as the gel base). Animals from each group were sacrificed on days 0, 3, 6, and 10 for collecting blood and ulcer tissue samples. Healing properties of oral gel were determined by clinical evaluation, as well as biochemical and histopathological examinations. Our findings suggest a significant decrease in the ulcer size in GVL gel group, with healing effects achieved through the alleviation of oxidative stress, reduction in COX-2 immunopositivity, and increase in collagen content in buccal tissue. Significant ulcer repairing potential of GVL gel highlights this oral mucoadhesive gel as a promising tool for prevention and treatment of RAS.

Normotensive rats with PCOS exhibit the hypertensive pattern: focus on oxidative stress.

Numerous evidence implies complex interrelations between polycystic ovary syndrome (PCOS) and hypertension (HT) in reproductive-age women. In this study, we aimed to investigate the potential strain differences in ovarian morphology, hemodynamic, and biochemical characteristics in an androgen-induced PCOS rat model. A total of 24 rats of 3 weeks old (12 Wistar Kyoto - WK and 12 spontaneously hypertensive rats - SHR) were divided into four groups: WK, WK PCOS, SHR, and SHR PCOS. PCOS was induced by daily s.c. injections of testosterone enanthate (1 mg/100 g body weight) administered for 5 weeks. PCOS induction led to estrus cyclicity cessation, cystic ovarian appearance, and sex hormones disturbances in both strains. The morphometric parameters in ovaries were altered in a manner of PCOS-related changes in both strains (higher number in preantral, atretic, and cystic follicles). Ultrasonographically, a significant decrease in ovarian volume (OV) was registered in PCOS groups but also in SHR compared to WK rats. All blood pressure parameters were higher in SHR compared to WK. PCOS modeling increased systolic, mean arterial, and pulse pressure in WK strain, while in SHR, only mean arterial and pulse pressure were higher. Alterations in oxidative stress parameters could provide a molecular basis for PCOS-related changes: in PCOS groups, thiobarbituric acid reactive substance and superoxide anion radical levels were higher in both strains, while superoxide dismutase and glutathione were significantly lowered.

Redox and apoptotic potential of novel ruthenium complexes in rat blood and heart.

Ruthenium(II) complexes offer the potential for lower toxicity compared with platinum(II) complexes. Our study aimed to compare cardiotoxicity of [Ru(Cl-tpy)(en)Cl][Cl], [Ru(Cl-tpy)(dach)Cl][Cl], [Ru(Cl-tpy)(bpy)Cl][Cl], cisplatin, and saline through assessment of redox status and relative expression of apoptosis-related genes. A total of 40 Wistar albino rats were divided into five groups. Ruthenium groups received a single dose of complexes intraperitoneally (4 mg/kg/week) for a 4-week period; cisplatin group received cisplatin (4 mg/kg/week) and control group received saline (4 mL/kg/week) in the same manner as ruthenium groups. In collected blood and heart tissue samples, spectrophotometric determination of oxidative stress biomarkers was performed. The relative expression of apoptosis-related genes (Bcl-2, Bax, and caspase-3) in hearts was examined by real-time polymerase chain reaction. Our results showed that systemic and cardiac pro-oxidative markers (thiobarbituric acid reactive substances and nitrite) were significantly lower in ruthenium groups compared with cisplatin group, while concentrations of antioxidative parameters (catalase, superoxide dismutase, and oxidized glutathione) were significantly higher. Ruthenium administration led to significantly lower gene expression of Bax and caspase-3 compared with cisplatin-treated rats, while Bcl-2 remained unchanged. Applied ruthenium complexes have less pronounced potential for induction of oxidative stress-mediated cardiotoxicity compared with cisplatin. These findings may help for future studies that should clarify the mechanisms of cardiotoxicity of ruthenium-based metallodrugs.

High-protein diet and omega-3 fatty acids improve redox status in olanzapine-treated rats.

The present study aimed to estimate the effects of high-protein diet (PD)-isolated whey protein and omega-3 fatty acids-docosahexaenoic and eicosapentaenoic acid on oxidative parameters of rats treated with Olanzapine (OLZ). Experiments were carried out on 8-week-old Wistar albino male rats (n = 64) weighing 200 ± 20 g. By dietary and pharmacological treatment, all animals were divided into 8 groups: 1. CTRL group; 2. CTRL + OLZ group; 3. CTRL + FA group; 4. CTRL + OLZ + FA group; 5. PD group; 6. PD + OLZ group; 7. PD + FA group; 8. PD + OLZ + FA group. After 6 weeks of pharmacological/diet treatment, all animals were sacrificed to collect blood samples and determine the biomarkers of oxidative stress. The following oxidative stress markers were measured spectrophotometrically: superoxide anion radical (O2-), hydrogen peroxide (H2O2), nitric oxide (NO-), index of lipid peroxidation measured as TBARS, reduced glutathione, catalase and superoxide dismutase. The study has shown that Olanzapine treatment was associated with increased release of pro-oxidants and diminished activity of anti-oxidant markers. Additional supplementation with PD and FA succeeded in abolishing the negative influence in most of the measured parameters. However, these beneficial impacts were stronger in the case of their separate application, which could be the practical and clinical importance of these results.

Immunohistomorphometric and Hormonal Analysis of the Pituitary Gonadotropic Cells After Application of the Nandrolone Decanoate and Swimming Training in Adult Male Rats.

The aim of the study was to investigate the effects of chronic nandrolone decanoate treatment and/or swimming training on immunohistomorphometric parameters on rat pituitary gonadotropic cells. Male Wistar albino rats, 10 weeks old, were classified into four groups: control (T−N−), nandrolone (T−N+), swimming training (T+N−), and swimming training with nandrolone (T+N+). The T+ groups swam for 4 weeks, 1 h/day, 5 days/week. The N+ groups received nandrolone decanoate (20 mg/kg) once per week for 4 weeks. Pituitary tissue sections were processed and stained for immunohistochemical analysis and immunofluorescence. The volume density of luteinizing hormone (LH) cells was decreased by 48% in T−N+ and for 35% in the T+N+ group. The volume density of follicle-stimulating hormone (FSH) cells was decreased by 39% in T−N+ and for 30% in T+N+ compared to the control. Nandrolone alone, or combined with swimming training, decreased the number of LH/FSH cells compared to the control. The levels of the immunofluorescent signal of LH/FSH cells were increased in all experimental groups. Nandrolone alone decreased the serum level of LH by 17%, whereas swimming training alone increased FSH levels by 11% compared to the control. Serum levels of testosterone were increased in all experimental groups. Nandrolone alone, or combined with swimming training, decreased immunohistomorphometric parameters of gonadotropic cells, whereas the levels of immunofluorescent signal were increased.

Preconditioning with hyperbaric oxygen and calcium and potassium channel modulators in the rat heart.

The aim of this study was to establish the effect of combined therapy with hyperbaric oxygen (HBO2) therapy and verapamil, amlodipine or nicorandil on functional recovery and oxidative stress markers after ischemia in the isolated rat heart. The study included 48 rats (Wistar albino, male gender, eight weeks old, body weight 200±50g). All animals were exposed to HBO2 treatment over 14 days. Isolated heart rats were perfused by the Langendorff retrograde method at a constant coronary pressure of 70 cm H2O. After stabilization period the hearts were divided into the following groups: HBO2 group (animals exposed to only HBO2 preconditioning); HBO2 + verapamil; HBO2 + amlodipine; andHBO2 + nicorandil (animals pretreated with HBO2 and appropriate pharmacological agent). Afterward, the hearts in all groups were subjected to 20-minute global ischemia and 30-minute reperfusion. Parameters of heart function were registered, including maximum and minimum rate of pressure development, systolic and diastolic left ventricular pressure, heart rate and coronary flow. Levels of pro-oxidants such as index of lipid peroxidation, measured as thiobarbituric acid-reactive substances, nitrites, levels of superoxide anion radicals and hydrogen peroxide were determined in coronary venous effluent. Changes in cardiac tissue were evaluated by hematoxylin and eosin staining. Obtained results clearly indicate that blockage of calcium channel or the activation of adenosine triphosphate-sensitive potassium (KATP) in combination with HBO2 prevented ischemia/reperfusion-induced cardiac deleterious effects, thus contributing to improvement of functional recovery of the heart. However, future studies are certainly necessary for better understanding the mechanisms through which combination of these two maneuvers of preconditioning triggers cardioprotection.

An evaluation of the redox state in professional scuba divers.

Taking into consideration limited data regarding molecular interactions during and after diving, this investigation was intended to determine the oxidative status of divers before and after scuba diving by monitoring the oxidative status parameters. The prevalence study included a group of 32 male professional police scuba divers, 32 ± 5.1 years old. The examination took place twice: in a resting state before scuba diving and immediately after the dive (to 30 meters for 30 minutes). The oxidative status of the scuba divers was determined by measuring levels of the following oxidative stress markers: the index of lipid peroxidation (measured as TBARS), nitrites (NO2-), superoxide anion radical (O2*-), hydrogen peroxide (H2O2), superoxide dismutase (SOD) and catalase (CAT). Statistically significant increases in levels of NO2- and TBARS were observed after the dive, while there were no statistically relevant changes in levels of O2*-, H2O2, SOD and CAT. Our results have shown that a dive with these characteristics only slightly disturbs redox homeostasis, without serious intermolecular changes that can lead to prominent oxidative stress.

Effect of GLP-1 Receptor Agonist on Ischemia Reperfusion Injury in Rats with Metabolic Syndrome.

Metabolic syndrome (MetS) represents an important factor that increases the risk of myocardial infarction, and more severe complications. Glucagon Like Peptide-1 Receptor Agonists (GLP-1RAs) exhibit cardioprotective potential, but their efficacy in MetS-related myocardial dysfunction has not been fully explored. Therefore, we aimed to assess the effects of exenatide and dulaglutide on heart function and redox balance in MetS-induced rats. Twenty-four Wistar albino rats with induced MetS were divided into three groups: MetS, exenatide-treated (5 µg/kg), dulaglutide-treated (0.6 mg/kg). After 6 weeks of treatment, in vivo heart function was assessed via echocardiography, while ex vivo function was evaluated using a Langendorff apparatus to simulate ischemia-reperfusion injury. Heart tissue samples were analyzed histologically, and oxidative stress biomarkers were measured spectrophotometrically from the coronary venous effluent. Both exenatide and dulaglutide significantly improved the ejection fraction by 3% and 7%, respectively, compared to the MetS group. Histological analyses corroborated these findings, revealing a reduction in the cross-sectional area of cardiomyocytes by 11% in the exenatide and 18% in the dulaglutide group, indicating reduced myocardial damage in GLP-1RA-treated rats. Our findings suggest strong cardioprotective potential of GLP-1RAs in MetS, with dulaglutide showing a slight advantage. Thus, both exenatide and dulaglutide are potentially promising targets for cardioprotection and reducing mortality in MetS patients.

Phosphodiesterase-5 Inhibitors as Therapeutics for Cardiovascular Diseases: A Brief Review.

Background: Three selective and most used inhibitors of PDE-5-sildenafil, vardenafil and tadalafil- have been successfully used for the treatment of erectile dysfunction. Erectile dysfunction and cardiovascular diseases might be considered as two dissimilar clinical signs of the identical systemic disease. PDE-5 inhibitors can through different models and mechanisms induce vasodilation, decrease apoptosis and cell proliferation, and they are widely present in various tissues that make them promising targets in a range of cardiovascular diseases. Methods: PubMed was explored to identify papers published from 1990-2019, presenting data for the most used PDE-5 inhibitors (sildenafil, tadalafil or vardenafil) in treatment of cardiovascular diseases. Results: This article analyses the therapeutic potentials of PDE-5 inhibitors in cardiovascular diseases and discusses mechanisms, possible risks and limitations. Comparable to earlier studies, newer studies suggest cardioprotective effects of PDE-5 inhibitors, which include different models and mechanisms and do not indicate an increased rate of significant cardiovascular adverse reactions. Dissimilarity in the pharmacokinetics and pharmacodynamics of PDE-5 inhibitors are significant to their risk- benefit profile and clinical use. Some of the studies suggesting infarct size reduction after PDE-5 inhibition described the especially close dose-effect relation, other studies dosage adaptation in drug- drug interactions. Conclusion: PDE-5 inhibitors indicate the encouraging useful effects by ischemia/reperfusion injury, myocar-dial infarction, cardiac hypertrophy, cardiomyopathy and systolic and diastolic congestive heart failure. Therefore, this and similar reviews can help for additional clinical targeting in the therapy of cardiovascular diseases.

The Potential of SGLT-2 Inhibitors in the Treatment of Polycystic Ovary Syndrome: The Current Status and Future Perspectives.

Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy during women's reproductive age. PCOS is a heterogeneous disorder featuring specific cardiometabolic properties. The association between the presence of metabolic disorders and PCOS supports the claim that the regulation of glycemic status is very important in these patients. There is a wide range of therapeutic options (including those treating diabetes mellitus type 2) with potential advantages available for the management of PCOS. Sodium-glucose cotransporter type 2 inhibitors (SGLT-2is) improve glucose metabolism, reduce fat tissue, lower blood pressure, reduce oxidative stress and inflammation, and protect the cardiovascular system. Currently, the use of SGLT-2is is not widespread in PCOS therapy, although these drugs represent a promising new therapeutic approach. Therefore, it is necessary to initiate further study in order to determine more effective therapies for PCOS and investigate the effect of SGLT-2is, both as a monotherapy and in combination with other drugs. It is necessary to understand the mechanisms underlying SGLT-2is in PCOS and their effects on long-term complications, especially since the gold standard treatment for PCOS, such as metformin and oral contraceptives, do not have long-term cardioprotective effects. The effects of SGLT-2is seem to involve cardiac protection, while diminishing endocrine and reproductive abnormalities in PCOS. In the current narrative review, we examine the most recent clinical evidence and discuss the potential applications of SGLT-2is for PCOS therapy.

Short-Term Administration of Lemon Balm Extract Ameliorates Myocardial Ischemia/Reperfusion Injury: Focus on Oxidative Stress.

We aimed to investigate the cardioprotective effects of ethanolic Melissa officinalis L. extract (ME) in the rat model of myocardial ischemia/reperfusion (I/R) injury. Thirty-two Wistar rats were randomly divided into a CTRL non-treated control group with myocardial I/R injury and three experimental groups of rats treated with 50, 100, or 200 mg/kg of ME for 7 days per os. Afterward, hearts were isolated, and cardiodynamic function was assessed via the Langendorff model of global 20 min ischemia and 30 min reperfusion. Oxidative stress parameters were determined spectrophotometrically from the samples of coronary venous effluent (O2-, H2O2, TBARS, and NO2-,) and heart tissue homogenate (TBARS, NO2-, SOD, and CAT). H/E and Picrosirius red staining were used to examine cardiac architecture and cardiac collagen content. ME improved cardiodynamic parameters and achieved to preserve cardiac architecture after I/R injury and to decrease fibrosis, especially in the ME200 group compared to CTRL. ME200 and ME100 markedly decreased prooxidants TBARS, O2-, and H2O2 while increasing NO2-. Hereby, we confirmed the ME`s ability to save the heart from I/R induced damage, even after short-term preconditioning in terms of preserving cardiodynamic alterations, cardiac architecture, fibrosis, and suppressing oxidative stress, especially in dose of 200 mg/kg.

Antioxidative Effects of Standardized Aronia melanocarpa Extract on Reproductive and Metabolic Disturbances in a Rat Model of Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) represents the most common endocrinopathy among childbearing-age women, with oxidative stress (OS) underlying its etiopathogenesis. Metformin (MET) represents a frequently used agent in PCOS. However, weak results encourage alternative treatments. We aimed to investigate isolated and synergistic effects of Standardized Aronia melanocarpa extract (SEA) and MET for alleviating reproductive and metabolic PCOS abnormalities. PCOS induction was followed by 28-day treatment with MET, SAE, or MET + SEA. Bodyweight (BW), cyclicity, histological, and ultrasonographical ovarian analyses were performed. Hormonal, glycemic, and lipid profiles were accessed, as well as systemic and ovarian oxidative status; BW, cyclicity, ovarian histomorphology, ovarian volume, testosterone and progesterone levels, as well as LDL, triglycerides, and total cholesterol levels were aggravated after PCOS-induction and improved after MET, SEA, and MET + SEA treatment. MET + SEA had the greatest impact on glycoregulation. Alterations in OS parameters (TBARS, O2-, H2O2, catalase, superoxide dismutase, and reduced glutathione) could be responsible for observed differences; (4) Conclusions: Our findings confirmed that SAE alone or along with MET was capable of ameliorating reproductive and metabolic disturbances in the PCOS rat model, with the restoration of OS parameters. SAE alone did not alter the protective effects of MET in PCOS.

Nandrolone Decanoate and Swimming Affects Cardiodynamic and Morphometric Parameters in the Isolated Rat Heart.

(1) Background: The aim of this study was to show the effects of swimming and nandrolone administration on cardiodynamic and morphometric parameters of the isolated rat heart. (2) The study included 72 Wistar rats, divided into three groups, scheduled to be sacrificed after the second, third, and fourth week. Each group was divided into four subgroups: control (T-N-), nandrolone (T-N+), swimming training (T+N-), and swimming training plus nandrolone (T+N+) group. The rats from T+N- and T+N+ swam 1 h/day, 5 days/week while ones from T-N+ and T+N+ received weekly nandrolone decanoate (20 mg/kg). The isolated hearts were perfused according to the Langendorff technique and measured parameters: dp/dt max/min, SLVP, DLVP, heart rate, and coronary flow. Hearts were fixed and stained with H/E and Masson trichrome dyes. (3) dp/dt max and dp/dt min were increased in the T-N+ group at higher perfusion pressure compared to the T-N- group. SLVP and DLVP were increased in all groups after the 4th week. Collagen content was increased in T-N+ by 403% and in T+N+ by 357% groups, while it was decreased in T+N- compared to the control after 4th week. (4) Conclusions: Nandrolone alone or combined with swimming had a deleterious effect on myocardial function and perfusion.

Melissa officinalis L. Supplementation Provides Cardioprotection in a Rat Model of Experimental Autoimmune Myocarditis.

Due to existing evidence regarding antioxidant and anti-inflammatory effects of Melissa officinalis extracts (MOEs), this study was aimed at investigating the potential of ethanolic MOE to prevent the development of myocarditis and its ability to ameliorate the severity of experimental autoimmune myocarditis (EAM) by investigating MOE effects on in vivo cardiac function, structure, morphology, and oxidative stress parameters. A total of 50 7-week-old male Dark Agouti rats were enrolled in the study and randomly allocated into the following groups: CTRL, nontreated healthy rats; EAM, nontreated rats with EAM; MOE50, MOE100, and MOE200, rats with EAM treated with either 50, 100, or 200 mg/kg of MOE for 3 weeks per os. Myocarditis was induced by immunization of the rats with porcine myocardial myosin (0.5 mg) emulsion on day 0. Cardiac function and dimensions of the left ventricle (LV) were assessed via echocardiography. Additionally, the blood pressure and heart rate were measured. On day 21, rats were sacrificed and the hearts were isolated for further histopathological analyses (H/E and Picrosirius red staining). The blood samples were collected to determine oxidative stress parameters. The EAM group characteristically showed greater LV wall thickness and lower ejection fraction (50.33 ± 7.94% vs. 84.81 ± 7.74%) and fractional shortening compared to CTRL (p < 0.05). MOE significantly improved echocardiographic parameters (EF in MOE200 81.44 ± 5.51%) and also reduced inflammatory infiltrate (by 88.46%; p < 0.001) and collagen content (by 76.39%; p < 0.001) in the heart tissues, especially in the MOE200 group compared to the EAM group. In addition, MOEs induced a significant decrease of prooxidants production (O2 -, H2O2, and TBARS) and improved antioxidant defense system via increase in GSH, SOD, and CAT compared to EAM, with medium and high dose being more effective than low dose (p < 0.05). The present study suggests that ethanolic MOEs, especially in a 200 mg/kg dose, improve cardiac function and myocardial architecture, possibly via oxidative stress mitigation, thus preventing heart remodeling, development of dilated cardiomyopathy, and subsequent heart failure connected with EAM. MOEs might be considered as a potentially helpful adjuvant therapy in patients with autoimmune myocarditis.

Morphometric analysis and redox state of the testicles in nandrolone decanoate and swimming treated adult male rats.

BACKGROUND: During the last decades, the abuse of anabolic androgenic steroids (AASs) has become popular among professional and recreational athletes. The abuse of AASs leads to decreased levels of sex hormones, but the available literature a gives very small pool of data regarding the effects of swimming alone or combined with AASs on testicle tissue. The aim of this study was to investigate the effects of four-week administration of nandrolone decanoate and swimming training alone or in combination on morphometric parameters, androgen receptor (AR) and redox state in testicle tissue. The study included Wistar albino male rats, 10 weeks old, classified into 4 groups: control (T-N-), nandrolone (T-N+), swimming training (T+N-) and swimming training with nandrolone (T+N+). The rats from nandrolone (N+) groups received nandrolone decanoate 20 mg/kg b.w.once per week. The rats from training (T+) groups, swam 1 h/day 5 days/week. The isolated testicles were measured, left testicles were routinely processed for histological analysis, while right testicles were homogenized and prepared for the analysis of the following oxidative stress biomarkers: index of lipid peroxidation (TBARS), nitrites, catalase, superoxide dismutase (SOD), and reduced glutathione (GSH). RESULTS: Diameter, as well as cross-section area of seminiferous tubules were decreased by 10 % and 21 % (respectively) in the T-N+ group and by 15% and 41 % (respectively) in the T+N+ group compared to control. Interstitium of the testicles was decreased in all experimental groups. Reduction of immunoreactivity of AR in T-N+ group was 22 %, in T+N+ group was 9 % compared to control. TBARS levels were increased in T+N- and T+N+ groups. Nitrites were decreased in T+N+ group. Catalase activity was increased in all experimental groups. Swimming alone or combined with nandrolone decreased the level of GSH compared to control. SOD activity was decreased in T-N+ and T+N+ groups compared to control. CONCLUSIONS: Nandrolone alone or combined with swimming decreased morphometric parameters and amount of AR in testicle tissue. Changes in the redox state indicate reproductive dysfunction.

RéSUMé: CONTEXTE: Au cours des dernières décennies, l'abus de stéroïdes androgéniques anabolisants (SAA) est devenu populaire parmi les athlètes professionnels et récréatifs. L'abus des SAA conduit à une diminution des niveaux d'hormones sexuelles, mais la littérature sur les effets de la natation seule ou combinée avec des SAA sur les tissus testiculaires est encore très limité. Le but de cette étude était d'étudier les effets de l'administration de quatre semaines de décanoate de nandrolone et de l'entraînement à la natation seuls ou en combinaison sur les paramètres morphométriques, le récepteur aux androgènes (RA) et l'état redox dans le tissu testiculaire. L'étude a inclus des rats mâles Wistar albinos, âgés de 10 semaines, classés en 4 groupes: contrôle (T-N-), nandrolone (T-N+), entraînement à la natation (T+N-) et entraînement à la natation avec nandrolone (T+N+). Les rats des groupes nandrolone (N+) ont reçu du décanoate de nandrolone 20 mg/kg p.c. une fois par semaine. Les rats des groupes entraînement (T+) nageaient 1 h/jour 5 jours/semaine. Les testicules isolés ont été mesurés, les testicules gauches ont été systématiquement traités pour l'analyse histologique tandis que les testicules droits ont été homogénéisés et préparés pour l'analyse des biomarqueurs de stress oxydatif suivants: indice de peroxydation lipidique (TBARS), nitrites, catalase, superoxyde dismutase (SOD) et glutathion réduit (GSH). RéSULTATS: Le diamètre, ainsi que la section transversale des tubules séminifères ont été réduits de 10 % et 21 % (respectivement) dans le groupe T-N+ et de 15 % et 41 % (respectivement) dans le groupe T+N+ par rapport au groupe témoin. L'interstitium des testicules était diminué dans tous les groupes expérimentaux. La réduction de l'immunoréactivité de RA dans le groupe T-N+ était de 22 %, dans le groupe T+N+ était de 9 % par rapport au groupe témoin. Les niveaux de TBARS ont augmenté dans les groupes T+N- et T+N+. Les nitrites ont diminué dans le groupe T+N+. L'activité de la catalase a été augmentée dans tous les groupes expérimentaux. La natation seule ou combinée à la nandrolone a réduit le niveau de GSH par rapport au contrôle. L'activité de la SOD était diminuée dans les groupes T-N+ et T+N+ par rapport au contrôle. CONCLUSIONS: La nandrolone seule ou combinée à la natation a diminué les paramètres morphométriques et la quantité de RA dans le tissu testiculaire. Les changements de l'état redox indiquent un dysfonctionnement de la reproduction.

New Insight Into the Cardioprotective Effects of Allium ursinum L. Extract Against Myocardial Ischemia-Reperfusion Injury.

This study aimed to estimate the effects of increasing doses of Allium ursinum methanol extract on cardiac ischemia/reperfusion injury (I/R) with a special emphasis on the role of oxidative stress. Fifty rats were randomly divided into five groups (10 animals per group) depending on the applied treatment as follows: sham, rats who drank only tap water for 28 days and hearts were retrogradely perfused for 80 min without I/R injury, I/R, rats who drank only tap water for 28 days and hearts were exposed to ex vivo I/R injury and rats who consumed increasing doses of A. ursinum 125, 250, and 500 mg/kg for 28 days before I/R injury. Hearts from all rats were isolated and retrogradely perfused according to the Langendorff technique. Parameters of oxidative stress were spectrophotometrically measured in blood, coronary venous effluent, and heart tissue samples. Intake of wild garlic extract for 28 days significantly contributed to the recovery of cardiac function, which was reflected through preserved cardiac contractility, systolic function, and coronary vasodilatory response after ischemia. Also, wild garlic extract showed the potential to modulate the systemic redox balance and stood out as a powerful antioxidant. The highest dose led to the most efficient decrease in cardiac oxidative stress and improve recovery of myocardial function after I/R injury. We might conclude that wild garlic possesses a significant role in cardioprotection and strong antioxidant activity, which implicates the possibility of its use alone in the prevention or as adjuvant antioxidant therapy in cardiovascular diseases (CVD).