A Comprehensive Overview on Chemotherapy-Induced Cardiotoxicity: Insights into the Underlying Inflammatory and Oxidative Mechanisms.

While oncotherapy has made rapid progress in recent years, side effects of anti-cancer drugs and treatments have also come to the fore. These side effects include cardiotoxicity, which can cause irreversible cardiac damages with long-term morbidity and mortality. Despite the continuous in-depth research on anti-cancer drugs, an improved knowledge of the underlying mechanisms of cardiotoxicity are necessary for early detection and management of cardiac risk. Although most reviews focus on the cardiotoxic effect of a specific individual chemotherapeutic agent, the aim of our review is to provide comprehensive insight into various agents that induced cardiotoxicity and their underlying mechanisms. Characterization of these mechanisms are underpinned by research on animal models and clinical studies. In order to gain insight into these complex mechanisms, we emphasize the role of inflammatory processes and oxidative stress on chemotherapy-induced cardiac changes. A better understanding and identification of the interplay between chemotherapy and inflammatory/oxidative processes hold some promise to prevent or at least mitigate cardiotoxicity-associated morbidity and mortality among cancer survivors.

A stepwise one-pot synthesis of aliphatic thiols and their derivatives from acrylamides and sulfur.

Elemental sulfur enables the convenient formation of C-S bonds and the direct incoporation of S-S bonds. The reactivity of easily accessible electron deficient alkenes towards sulfur, however, is barely disclosed. Herein, we investigated the reactivity of acrylamides with sulfur and eventually developed a new pseudo-multicomponent reaction for the preparation of polysulfides. Sequential one-pot reduction led to diversely substituted thiols. Additional third stage one-pot modifications provided thioethers, unsymmetric disulfide and thioester.

Exercise-mitigated sex-based differences in aging: from genetic alterations to heart performance.

The prevalence of cardiovascular diseases dramatically increases with age; therefore, striving to maintain a physiological heart function is particularly important. Our aim was to study the voluntary exercise-evoked cardioprotective effects in aged male and female rats, from genetic alterations to changes in heart performance. We divided 20-month-old female and male Wistar rats to control and running groups. After the 12-wk-long experimental period, echocardiographic measurements were performed. Afterwards, hearts were either removed for biochemical measurements or mounted into a Langendorff-perfusion system to detect infarct size. The following genes and their proteins were analyzed from heart: catechol-O-methyltransferase (Comt), endothelin-1 (Esm1), Purkinje cell protein-4 (Pcp4), and osteoglycin (Ogn). Recreational exercise caused functional improvements; however, changes were more prominent in males. Cardiac expression of Comt and Ogn was reduced as a result of exercise in aged males, whereas Pcp4 and Esm1 showed a marked overexpression, along with a markedly improved diastolic function. The key result of this study is that exercise enhanced the expression of the Pcp4 gene and protein, a recently described regulator of calcium balance in cardiomyocytes, and suppressed Comt and Ogn gene expression, which has been associated with impaired cardiac function. In addition, as a result of exercise, a significant improvement was observed in the size of infarct elicited by left anterior descending coronary artery occlusion. Our results clearly show that age and sex-dependent changes were both apparent in key proteins linked to cardiovascular physiology. Exercise-moderated fundamental genetic alterations may have contributed to the functional adaptation of the heart.NEW & NOTEWORTHY Voluntary exercise has proved to be an effective therapeutic tool to improve cardiac function in aged rats with clearly visible sex differences. Long-term exercise is associated with decreased Ogn and Comt expression and enhanced presence of Pcp4 and Esm1 genes. Sex-dependent changes were also observed in the expression of the cardiovascular key proteins. Fundamental alterations in gene and protein expression may contribute to the improvement of cardiac performance.

Continuous-Flow Synthesis of Thioureas, Enabled by Aqueous Polysulfide Solution.

We have developed the continuous-flow synthesis of thioureas in a multicomponent reaction starting from isocyanides, amidines, or amines and sulfur. The aqueous polysulfide solution enabled the application of sulfur under homogeneous and mild conditions. The crystallized products were isolated by simple filtration after the removal of the co-solvent, and the sulfur retained in the mother liquid. Presenting a wide range of thioureas synthesized by this procedure confirms the utility of the convenient continuous-flow application of sulfur.

A Potential Involvement of Anandamide in the Modulation of HO/NOS Systems: Women, Menopause, and "Medical Cannabinoids".

Endocannabinoids and their receptors are present in the cardiovascular system; however, their actions under different pathological conditions remain controversial. The aim of our study was to examine the effects of anandamide (AEA) on heme oxygenase (HO) and nitric oxide synthase (NOS) systems in an estrogen-depleted rat model. Sham-operated (SO) and surgically induced estrogen-deficient (OVX) female Wistar rats were used. During a two-week period, a group of OVX rats received 0.1 mg/kg estrogen (E2) per os, while AEA-induced alterations were analyzed after two weeks of AEA treatment at the dose of 1.0 mg/kg. At the end of the experiment, cardiac activity and expression of HO and NOS enzymes, content of cannabinoid 1 receptor, as well as concentrations of transient potential vanilloid 1 (TRPV1) and calcitonin gene-related peptide (CGRP) were measured. Our results show that estrogen withdrawal caused a significant decrease in both NOS and HO systems, and a similar tendency was observed regarding the TRPV1/CGRP pathway. Two weeks of either AEA or E2 treatment restored the adverse changes; however, the combined administration of these two molecules did not result in a further improvement. In light of the potential relationship between AEA and HO/NOS systems, AEA-induced upregulation of HO/NOS enzymes may be a therapeutic strategy in estrogen-deficient conditions.

Imidazo[1,2-b]pyrazole-7-Carboxamide Derivative Induces Differentiation-Coupled Apoptosis of Immature Myeloid Cells Such as Acute Myeloid Leukemia and Myeloid-Derived Suppressor Cells.

Chemotherapy-induced differentiation of immature myeloid progenitors, such as acute myeloid leukemia (AML) cells or myeloid-derived suppressor cells (MDSCs), has remained a challenge for the clinicians. Testing our imidazo[1,2-b]pyrazole-7-carboxamide derivative on HL-60 cells, we obtained ERK phosphorylation as an early survival response to treatment followed by the increase of the percentage of the Bcl-xlbright and pAktbright cells. Following the induction of Vav1 and the AP-1 complex, a driver of cellular differentiation, FOS, JUN, JUNB, and JUND were elevated on a concentration and time-dependent manner. As a proof of granulocytic differentiation, the cells remained non-adherent, the expression of CD33 decreased; the granularity, CD11b expression, and MPO activity of HL-60 cells increased upon treatment. Finally, viability of HL-60 cells was hampered shown by the depolarization of mitochondria, activation of caspase-3, cleavage of Z-DEVD-aLUC, appearance of the sub-G1 population, and the leakage of the lactate-dehydrogenase into the supernatant. We confirmed the differentiating effect of our drug candidate on human patient-derived AML cells shown by the increase of CD11b and decrease of CD33+, CD7+, CD206+, and CD38bright cells followed apoptosis (IC50: 80 nM) after treatment ex vivo. Our compound reduced both CD11b+/Ly6C+ and CD11b+/Ly6G+ splenic MDSCs from the murine 4T1 breast cancer model ex vivo.

Postconditioning-like effect of exercis: new paradigm in experimental menopause.

The progression of coronary artery diseases in premenopausal women is lower than in age-matched men; however, its probability increases rapidly after menopause. The aim of our study was to investigate the postconditioning-like effects of voluntary physical exercise on postmenopausal cardiovascular outcomes after myocardial infarction. We used fertile Wistar females [control (CTRL)] and pharmacologically induced estrogen-deficient (POVX; 750 µg/kg triptorelin im, every 4th week) rats. CTRL and POVX animals were randomly assigned to receive an injection of 0.1 mg isoproterenol (ISO)/kg. At the 20th hour after ISO injection, serum markers of myocardial injury, such as lactate dehydrogenase (LDH) and myoglobin, were measured. After a 3-wk resting period, ISO-treated and untreated animals were further divided into subgroups on the basis of 6 wk of physical exercise. At the end of the experiment, cardiac activity and content of the antioxidative heme oxygenase (HO) enzyme, levels of GSH and GSH + GSSG, activity of myeloperoxidase, as well as the concentration of TNF-α were determined. At the end of the experimental period, we observed a significant decrease in the activity and content of HO enzymes in POVX and POVX/ISO rats, whereas physical exercise significantly improved HO and GSH values in both CTRL and POVX rats. Furthermore, our training protocol significantly reduced the pathological levels of myeloperoxidase and TNF-α. Our findings clearly demonstrate that modulation of the HO system by voluntary physical exercise is a key process to decrease inflammatory parameters and ameliorate the antioxidative status in estrogen-deficient conditions postmyocardial injury. NEW & NOTEWORTHY We used a noninvasive rat model of estrogen deficiency and myocardial infarction. The long-term effects of isoproterenol treatment revealed reduced heme oxygenase enzyme activity and expression and decreased glutathione levels. Isoproterenol treatment enhanced the myeloperoxidase enzyme activity. Voluntary physical exercise ameliorated the antioxidative status by increasing of the heme oxygenase enzyme system. Voluntary physical exercise is a potential therapeutic tool to improve cardiac antioxidant status in menopausal women postmyocardial injury.

New Metabolic Influencer on Oxytocin Release: The Ghrelin.

BACKGROUND: The hypothalamic⁻pituitary axis by secreting neuropeptides plays a key role in metabolic homeostasis. In light of the metabolic regulation, oxytocin is a potential neuropeptide for therapies against obesity and related disorders. The aim of our study is to measure ghrelin-induced oxytocin secretion in rats and to detect the changes after administration of ghrelin antagonist. METHODS: Ghrelin was administrated centrally (intracerebroventricular, i.c.v., 1.0, 10.0, and 100.0 pmol) or systemically (intravenous, i.v., 1.0, and 10.0 nmol). [d-Lys³]-GHRP-6 ghrelin antagonist was injected 15 min before ghrelin injection in a dose of 10.0 pmol i.c.v. and 10.0 nmol i.v. RESULTS: Either i.c.v. or i.v. administration of ghrelin dose-dependently increased the plasma oxytocin concentration. Following pretreatment with the ghrelin antagonist [d-Lys³]-GHRP-6, the high plasma oxytocin level induced by ghrelin was significantly reduced. CONCLUSION: The results indicate that the release of oxytocin is influenced directly by the ghrelin system. Examination of the mechanism of ghrelin-induced oxytocin secretion is a new horizon for potential therapeutic options.

Novel Potentials of the DPP-4 Inhibitor Sitagliptin against Ischemia-Reperfusion (I/R) Injury in Rat Ex-Vivo Heart Model.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of oral anti-diabetic drugs, implicated in pleiotropic secondary cardioprotective effects. The aim of the study was to unveil the unknown and possible cardioprotective targets that can be exerted by sitagliptin (Sitg) against ischemia-reperfusion (I/R) injury. Male wistar rats received 2 weeks' Sitg oral treatment of different doses (25, 50, 100, and 150 mg/kg/day), or saline as a Control. Hearts were then isolated and subjected to two different I/R injury protocols: 10 min perfusion, 45 min regional ischemia, and 120 min reperfusion for infarct size (IS) measurement, or: 10 min perfusion, 45 min regional ischemia and 10 min reperfusion for biochemical analysis: nitric oxide synthases (NOSs) and DPP-4 activity, glucagon-like peptide-1 (GLP-1), Calcium, transient receptor potential vanilloid (TRPV)-1 and calcitonin gene-related peptide (CGRP) levels, transient receptor potential canonical (TRPC)-1 and e-NOS protein expression. NOS inhibitor (L-NAME) and TRPV-1 inhibitor (Capsazepine) were utilized to confirm the implication of both signaling mechanisms in DPP-4 inhibition-induced at the level of IS. Findings show that Sitg (50 mg) resulted in significant decrease in IS and DPP-4 activity, and significant increase in GLP-1, NOS activity, e-NOS expression, TRPV-1 level and TRPC-1 expression, compared to controls. Results of CGRP are in line with TRPV-1, as a downstream regulatory effect. NOS system and transient receptor potential (TRP) channels can contribute to DPP-4 inhibition-mediated cardioprotection against I/R injury using Sitagliptin.

The Effects of Exercise Training and High Triglyceride Diet in an Estrogen Depleted Rat Model: The Role of the Heme Oxygenase System and Inflammatory Processes in Cardiovascular Risk.

Cardiovascular morbidity and mortality of premenopausal women are significantly lower compared to men of similar age. However, this protective effect evidently decreases after the onset of menopause. We hypothesized that physical exercise could be a potential therapeutic strategy to improve inflammatory processes and cardiovascular antioxidant homeostasis, which can be affected by the loss of estrogen and the adverse environmental factors, such as overnutrition. Ovariectomized (OVX, n= 40) and sham-operated (SO, n= 40) female Wistar rats were randomized to exercising (R) and non-exercising (NR) groups. Feeding parameters were chosen to make a standard chow (CTRL) or a high triglyceride diet (HT) for 12 weeks. Aortic and cardiac heme oxygenase (HO) activity and HO-1 concentrations significantly decreased in all of the NR OVX and SO HT groups. However, the 12-week physical exercise was found to improve HO-1 values. Plasma IL-6 concentrations were higher in the NR OVX animals and rats fed HT diet compared to SO CTRL rats. TNF-α concentrations were significantly higher in the NR OVX groups. 12 weeks of exercise significantly reduced the concentrations of both TNF-α and IL-6 compared to the NR counterparts. The activity of myeloperoxidase enzyme (MPO) was significantly increased as a result of OVX and HT diet, however voluntary wheel-running exercise restored the elevated values. Our results show that estrogen deficiency and HT diet caused a significant decrease in the activity and concentration of HO enzyme, as well as the concentrations of TNF-α, IL-6, and the activity of MPO. However, 12 weeks of voluntary wheel-running exercise is a potential non-pharmacological therapy to ameliorate these disturbances, which determine the life expectancy of postmenopausal women.

Protective Effect of Prunus Cerasus (Sour Cherry) Seed Extract on the Recovery of Ischemia/Reperfusion-Induced Retinal Damage in Zucker Diabetic Fatty Rat.

Among diabetes patients, ophthalmological complications are very frequent. High blood glucose and (consequential) ischemia-reperfusion (I/R) injury contribute significantly to the severity of retinopathies. Diabetic retinopathy is among the leading causes of blindness. Our study demonstrates the effect of sour cherry seed extract (SCSE) on blood glucose and function of the retina with electroretinography (ERG) in a diabetic setting with or without ischemia-reperfusion (I/R) injury in Zucker Diabetic Fatty (ZDF) rats. Our results prove that the SCSE has a retinoprotective effect in diabetic rats: according to ERG measurements, SCSE treatment mitigated the retinal function-damaging effect of diabetes, and proved to be protective in the diabetic eye against ischemia-reperfusion injuries of the retina. Outcomes suggest that the protective effects of SCSE may occur through several pathways, including HO-1 dependent mechanisms. The observation that SCSE treatment decreases blood glucose is also novel. These findings offer the possibility for development of novel therapeutic strategies utilizing this emerging functional food, in particular in the prevention of conditions resulting from high blood glucose or I/R injury, such as deterioration of retinal microcirculation.

Mechanisms and Target Parameters in Relation to Polycystic Ovary Syndrome and Physical Exercise: Focus on the Master Triad of Hormonal Changes, Oxidative Stress, and Inflammation.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder among females of reproductive age with heterogeneous prevalence. It is well known that female reproductive competence depends on the dynamic regulation of the hypothalamic-pituitary-gonadal (HPG) axis; therefore, disruption of this highly regulated system leads to fertility problems. Among disruptors, both oxidative stress and inflammation contribute to an increased LH-FSH ratio and a consequent hyperandrogenism. Shifts in this bidirectional interplay between the neuroendocrine system and oxidative/inflammatory homeostasis result in the accumulation of reactive oxygen/nitrogen species and inflammatory markers as well as alterations in antioxidant defense mechanisms. Evidence shows that lifestyle changes, including regular physical exercise, are recognized as the most effective first-line management to reduce the severity of PCOS symptoms. The aim of our narrative review is to provide insights into the mechanisms and target factors of PCOS-related hormonal changes, oxidative/antioxidant homeostasis, and inflammation, and to discuss the effects of exercise, which takes into account various factors, in relation to PCOS. A better understanding of the PCOS-associated hormonal changes, oxidative and inflammatory circuits, as well as exercise-induced mechanisms of action on those targets may improve the quality of life of women with PCOS.

[Thermal imaging and velocity measurements of the exhaled airflow in total laryngectomized patients during COVID-19 pandemic.] / Különbözo védoeszközök hokamerás vizsgálata és a kilélegzett levego sebességének mérése teljes gégeeltávolításon átesett betegekben COVID­19-pandémia idején.

INTRODUCTION: In patients after total laryngectomies, the trachea and the lung can be easily infected by SARS-CoV-2 because the respiration happens through the tracheostoma. OBJECTIVE: The aim of our study was to examine whether patients with LaryTube™ can distribute aerosols to a greater extent than without LaryTube™, and to observe whether the surface of different protective instruments can be examined using the thermal camera in total laryngectomees. An important objective was also to confirm the assumption that the use of HME (heat and moisture exchanger) alone does not provide protection during COVID-19 pandemic. Finally, during our tests, we tried to get an answer to our assumption that the sample taken from the inner surface of the HME can be tested for SARS-CoV-2. METHOD: A total of 23 patients who underwent total laryngectomies were analyzed by velocity measurements and thermal imaging with and without HMEs and laryngeal tubes, using different types of PPEs. COVID-19 PCR testing was performed on patient tracheas and the inner surfaces of the HMEs. RESULTS: Male patients with laryngeal tubes without HMEs demonstrated an increase in exhaled airflow velocity of more than 43% compared to male patients without laryngeal tubes; in female patients, the same value was more than 39%. Thermal imaging results confirmed that the lowest surface temperature was measured on FFP2 masks. The sent samples can be tested for SARS-CoV-2 using PCR, the presence of the virus was not detected. CONCLUSION: Laryngectomized patients without laryngeal tubes pose a lower risk for spreading viral aerosols due to the reduced velocity of the exhaled airflow caused by the absence of the tube as the narrowing factor. Patients with laryngeal tubes who undergo total laryngectomies during the COVID-19 pandemic should use HMEs with viral filter, if possible, also changing the laryngeal tubes to dermal adhesives for fitting their HMEs seems to be the best option. The surface of the used protective equipment can also be examined with thermal camera in the case of total laryngectomees. COVID-19 PCR testing of the tracheal secretion from the inner HME surfaces should become a routine in clinical practice if deemed necessary. Orv Hetil. 2023; 164(34): 1327-1336.

Protective Effects of H2S Donor Treatment in Experimental Colitis: A Focus on Antioxidants.

Inflammatory bowel diseases (IBD) are chronic, inflammatory disorders of the gastrointestinal (GI) system, which have become a global disease over the past few decades. It has become increasingly clear that oxidative stress plays a role in the pathogenesis of IBD. Even though several effective therapies exist against IBD, these might have serious side effects. It has been proposed that hydrogen sulfide (H2S), as a novel gasotransmitter, has several physiological and pathological effects on the body. Our present study aimed to investigate the effects of H2S administration on antioxidant molecules in experimental rat colitis. As a model of IBD, 2,4,6-trinitrobenzenesulfonic acid (TNBS) was used intracolonically (i.c.) to induce colitis in male Wistar-Hannover rats. Animals were orally treated (2 times/day) with H2S donor Lawesson's reagent (LR). Our results showed that H2S administration significantly decreased the severity of inflammation in the colons. Furthermore, LR significantly suppressed the level of oxidative stress marker 3-nitrotyrosine (3-NT) and caused a significant elevation in the levels of antioxidant GSH, Prdx1, Prdx6, and the activity of SOD compared to TNBS. In conclusion, our results suggest that these antioxidants may offer potential therapeutic targets and H2S treatment through the activation of antioxidant defense mechanisms and may provide a promising strategy against IBD.

The Interplay of Lifestyle and Adipokines in the Non-Obese Stroke-Prone Spontaneously Hypertensive Rats.

Although the morphological features and functions of adipose tissue are well-described in obesity-prone animal models, less information is available on animals such as the stroke-prone spontaneously hypertensive (SHRSP) strain with cardiovascular abnormalities, which is not characterized by excessive adiposity. Our aim was to focus on lifestyle-induced (type of diet and physical exercise) effects on adipokine profile and lipid peroxidation in SHRSP rats. In our study, male Wistar-kyoto (control) and SHRSP rats were used. SHRSP rats were fed either standard chow or a high-fat diet with 40% fat content (HFD). One group of the animals was placed into cages fitted with a running-wheel; thus, the dietary and training period started at the same time and lasted for 12 weeks. At the end of the experimental period, adiponectin, leptin, omentin, and chemerin concentrations were determined from adipose tissue and serum. Besides adipokines, malondialdehyde (MDA) levels were also measured. Twelve weeks of HFD significantly decreased adiponectin and omentin concentrations of both adipose tissue and serum, which were ameliorated by physical exercise. Serum leptin, chemerin, and MDA values were elevated in HFD groups; however, physical exercise was able to mitigate these adverse changes. Our results underpin the crosstalk between lifestyle changes and dysfunctional adipose tissue in SHRSP rats.

Voluntary Exercise-Mediated Protection in TNBS-Induced Rat Colitis: The Involvement of NETosis and Prdx Antioxidants.

Inflammatory bowel diseases (IBDs) are autoimmune disorders of the gut. It is increasingly clear that voluntary exercise (VE) may exert protection against IBDs, but the exact background mechanism needs to be elucidated. In the present study, we aimed to investigate the possible role of NETosis and the antioxidant peroxiredoxin (Prdx) enzyme family in VE-induced protection. Wistar Han rats were randomly divided into two groups: sedentary (SED) and VE. After the 6-week voluntary wheel running, animals were treated with 2,4,6-trinitrobenzene sulphonic acid (TNBS) as a model of colitis. Here, we found that VE significantly decreased inflammation and ulceration of the colon in the VE TNBS group compared with SED TNBS. We also found that VE significantly decreased the expression of protein arginine deiminase 4 (PAD4) and myeloperoxidase (MPO), and markedly reduced citrullinated histone H3 (citH3) compared with SED TNBS. Furthermore, VE caused a significant increase in the levels of Prdx6 in the control and TNBS groups. Taken together, we found that a prior 6-week VE effectively reduces inflammation in TNBS-induced colitis, and we suggest that the protective effect of VE may be mediated via the inhibition of NETosis and upregulation of Prdx6 antioxidant.

Resveratrol as a Promising Polyphenol in Age-Associated Cardiac Alterations.

According to a widely accepted theory, oxidative stress is considered to be the number one trigger of aging-associated degenerative processes including cardiovascular diseases. In the context of aging-research, resveratrol receives special attention with its surprising number of health benefits. The aim of our study was to examine the anti-inflammatory and antioxidant effects of this dietary polyphenol in aging rat heart. 20-month-old female and male Wistar rats were divided into control (untreated) and resveratrol-treated groups. Resveratrol was administered at a dose of 0.05 mg/ml for 12 weeks dissolved in drinking water, while the control rats received ad libitum water. Cardiac level of reactive oxygen species (ROS), nuclear factor kappa B (NFκB), tumor necrosis factor alpha (TNF-α), and glutathione (GSH) parameters, as well as the activity of myeloperoxidase (MPO) and heme oxygenase (HO) enzymes were detected. Together with the biochemical measurements, hearts were isolated and used for an exposure of ischemic-reperfusion injury via Langendorff perfusion system. 12 week of resveratrol treatment suppressed the age-related inflammatory pathways including the expression of TNF-α, NFκB, and the activity of MPO while intensified the endogenous antioxidant defenses through the induction of GSH and HO system. Presumably, as a result of these processes, the necrotic area of the heart in response to an acute injury was also significantly reduced in the resveratrol-treated groups. Our findings confirmed that resveratrol has cardioprotective effects at several points by counteracting the aging-associated cellular malfunctions in the heart.

Potential Implications of Rimonabant on Age-Related Oxidative Stress and Inflammation.

Over the last decades, growing interest has turned to preventive and therapeutic approaches for achieving successful aging. Oxidative stress and inflammation are fundamental features of cardiovascular diseases; therefore, potential targets of them can improve cardiac outcomes. Our study aimed to examine the involvement of the endocannabinoid system, especially the CB1 receptor blockade, on inflammatory and oxidant/antioxidant processes. Twenty-month-old female and male Wistar rats were divided into rimonabant-treated and aging control (untreated) groups. Rimonabant, a selective CB1 receptor antagonist, was administered at the dose of 1 mg/kg/day intraperitoneally for 2 weeks. Cardiac amounts of ROS, the antioxidant glutathione and superoxide dismutase (SOD), and the activity and concentration of the heme oxygenase (HO) enzyme were detected. Among inflammatory parameters, nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), and myeloperoxidase (MPO) enzyme activity were measured. Two weeks of low dose rimonabant treatment significantly reduced the cardiac ROS via boosting of the antioxidant defense mechanisms as regards the HO system, and the SOD and glutathione content. Consistently, the age-related inflammatory response was alleviated. Rimonabant-treated animals showed significantly decreased NF-κB, TNF-α, and MPO levels. Our findings prove the beneficial involvement of CB1 receptor blocker rimonabant on inflammatory and oxidative damages to the aging heart.

Andrological Aspects of Exercise: Moderate Swimming Protects against Isoproterenol Induced Testis and Semen Abnormalities in Rats.

The development and progression of male infertility are closely linked to a sedentary lifestyle; however, its underlying mechanisms are not fully elucidated. Our aim was to assess the protective effects of moderate swimming exercise on the male reproductive system in isoproterenol-treated rats. Male Wistar rats were divided into five groups as follows: (1) non-interventional controls (CTRL), (2) isoproterenol-treated (ISO), (3) pre-treatment swimming training + ISO (PRE + ISO), (4) ISO + post-treatment swimming training (ISO+POST), (5) pre-treatment swimming training + ISO + post-treatment swimming training (PRE + ISO + POST) groups. Testicular oxidative stress was induced by ISO injection (1.0 mg/kg). Rats in the pre- or post-training groups were trained five days a week. At the end of the experimental period, serum testosterone levels, sperms' hyaluronan binding, and total glutathione (GSH) content, as well as myeloperoxidase activity (MPO), TNF alpha and IL6 concentrations in the testis and semen, were measured. Serum testosterone levels, sperms' hyaluronan binding, and GSH content were found to be significantly reduced, while MPO, TNF alpha and IL6 concentrations in the testis and semen were elevated after the ISO treatment compared to the CTRL group. Moderate-intensity swimming exercise effectively alleviated the negative effects of high oxidative stress. Our findings provide the first evidence that moderate-intensity swimming exercise confers sustained protection from isoproterenol-induced adverse effects on testicular inflammation.

Chromatography-Free Multicomponent Synthesis of Thioureas Enabled by Aqueous Solution of Elemental Sulfur.

The development of a new three-component chromatography-free reaction of isocyanides, amines and elemental sulfur allowed us the straightforward synthesis of thioureas in water. Considering a large pool of organic and inorganic bases, we first optimized the preparation of aqueous polysulfide solution from elemental sulfur. Using polysulfide solution, we were able to omit the otherwise mandatory chromatography, and to isolate the crystalline products directly from the reaction mixture by a simple filtration, retaining the sulfur in the solution phase. A wide range of thioureas synthesized in this way confirmed the reasonable substrate and functional group tolerance of our protocol.