Bozidar Pindovic

Background/Objectives: Polyendocrine metabolic ovarian syndrome (PMOS) is a complex endocrine–metabolic disorder of multifactorial etiology, driven by interactions among hyperandrogenism, metabolic dysfunction, oxidative stress, and chronic low-grade inflammation that interact to promote reproductive dysfunction and increase risk of cardiometabolic complications. Although the combination of letrozole and high-fat diet (LET + HFD) represents a widely used experimental approach for inducing a PMOS-like phenotype in rats, its multisystem pathophysiological features remain incompletely characterized. The present study aimed to characterize reproductive, cardiometabolic, hormonal, inflammatory, oxidative, and morphometric alterations associated with a LET + HFD-induced PMOS-like phenotype in rats. Methods: PMOS-like model was induced in rats over a 21-day period of orally administered letrozole combined with a high-fat diet. Results: Body weight gain was higher, while uterine weight was lower in the PMOS group compared with controls. Metabolic parameters suggested insulin resistance, while hormonal profiling revealed increased total testosterone and LH levels, accompanied by reduced FSH, estradiol, and progesterone levels. Elevated triglycerides and reduced HDL levels were also observed in the PMOS group. Morphometric analysis revealed numerous atretic and large thin-walled cystic follicles in the ovaries, accompanied by thinning of the uterine luminal and glandular epithelium, stromal layer, and hypoplasia of endometrial glands. Both the longitudinal diameter and cross-sectional area of cardiomyocytes were increased in the PMOS group, together with nuclear hypertrophy and enhanced myocardial collagen deposition. In addition, altered oxidative stress markers, including increased lipid peroxidation and reduced glutathione levels, were observed, whereas IL-6, IL-1β, and IL-23 were not significantly altered. Conclusions: The LET + HFD model reproduces key reproductive and cardiometabolic features of PMOS, extending beyond reproductive dysfunction to involve oxidative and structural alterations in multiple organs. These findings support its use for investigating PMOS pathophysiology and evaluating potential preventive and therapeutic strategies.

Myocarditis is still a major global health issue that frequently manifests due to oxidative stress, immune-mediated myocardial damage, and unpredictable clinical progression. Experiments with autoimmune myocarditis (EAM) models have shown different ways that T-cell subsets, proinflammatory cytokines, macrophage polarization, and mitochondrial dysfunction are all connected and play a part in both acute inflammation and chronic remodeling of the heart. As a possible multimodal intervention that could affect several of these disease-causing pathways, hyperbaric oxygen therapy (HBOT) has become popular. This therapy delivers 100% oxygen to different tissues at higher atmospheric pressures. Early research shows that HBOT improves the delivery of oxygen to the inflamed myocardium, suppress the activation of NF-κB and NLRP3 inflammasomes, lowers oxidative stress, protects mitochondrial function, and boosts immune-regulatory T-cell responses. Despite these potentially promising findings, there are still a number of important translational obstacles to overcome, such as inconsistent protocols, a lack of long-term outcome data, insufficient mechanistic profiling, and doubts about the best protocol length and patient selection. To assess safety and effectiveness in human myocarditis, future studies should aim to integrate multi-omics analyses, HBOT regimens that are already standardized, sophisticated imaging, and carefully planned early-phase clinical trials. Overall, the currently available evidence supports HBOT as a biologically plausible and potentially valuable adjunct therapy for autoimmune myocarditis, expressing the need for further mechanistic and clinical investigation.

Myocarditis remains a significant global health burden often accompanied by im-mune-mediated myocardial injury, oxidative stress, and unpredictable clinical progres-sion. Experimental autoimmune myocarditis (EAM) models have provided different in-sights into the interconnected roles of T-cell subsets, proinflammatory cytokines, mac-rophage polarization, and mitochondrial dysfunction in both acute inflammation and chronic cardiac remodeling. Hyperbaric oxygen therapy (HBOT), which delivers 100% oxygen at elevated atmospheric pressures, has emerged as a potential multimodal in-tervention capable of affecting several of these pathogenic pathways. Preclinical data demonstrate that HBOT enhances oxygen delivery to the inflamed myocardium, sup-presses the activation of NF-κB and NLRP3 inflammasomes, reduces oxidative stress, preserves mitochondrial function, and promotes immunoregulatory T-cell responses. Despite these promising results, significant translational challenges remain, including protocol variability, lack of long-term outcome data, incomplete mechanistic profiling, and uncertainties regarding optimal timing and patient selection. Future research should try to incorporate already standardized HBOT regimens, multi-omics analyses, advanced imaging, and well-designed early-phase clinical trials to evaluate safety and efficacy in human myocarditis. Overall, the currently available evidence supports HBOT as a bi-ologically plausible and potentially valuable adjunct therapy for autoimmune myocar-ditis, expressing the need for further mechanistic and clinical investigation.

The aim of this study was to examine the potential antioxidant activity of curcumin in therapeutic and preventive condition and its potential role as adjuvant to conventional drug methotrexate in treatment of rheumatoid arthritis (RA). The study included 104 female Wistar albino rats, 6 weeks old, body weight of 200–250 g, which were divided into 8 groups (n=13 in each group): 1. CTRL: negative control, 2. CUR: positive control 1 (curcumin 200 mg/kg three times a week for 4 weeks per os), 3. MTX: positive control 2 (methotrexate 0,75 mg/kg i.p. two times a week for 4 weeks), 4. RA: positive control 3 (induced RA), 5. RA+pCUR: rats with induced RA + preventive administration of curcumin (curcumin 200 mg/kg three times a week for 4 weeks per os before the induction of RA), 6. RA+tCUR: rats with induced RA + curcumin therapy, 7. RA+MTX+pCUR; rats with induced RA + preventive administration of curcumin + methotrexate 0.75 mg/kg i.p. twice weekly for 4 weeks, 8. RA+MTX+tCUR: rats with induced RA + therapeutic administration of curcumin + methotrexate 0.75 mg/kg i.p. twice weekly for 4 weeks. Potential therapeutic effect of curcumin (200 mg/kg three times a week for 4 weeks orally) and RA induction were initiated on the same day; for preventive protocol, curcumin was administered 4 weeks before the start of RA induction at a dose of 200 mg/kg orally three times a week. Rheumatoid arthritis was triggered by administering 0.1 ml of Complete Freund’s Adjuvant (CFA) subcutaneously at the base of the rat tail. Rats were sacrificed 28 days after immunization. During the experimental period, we collected data for arthritis score, radiography testing, and blood sample collecting for specific biochemical analysis for prooxidative and antioxidative parameters (superoxide anion radical, hydrogen peroxide, nitric oxide, index of lipid peroxidation, superoxide dismutase, catalase, and reduced glutathione). Our experimental study confirmed that the therapeutic administration of curcumin reduced disease activity and significantly increased the activities of antioxidative enzymes and reduced prooxidants. Also, preventive administration, especially in combination with methotrexate, offers superior protection by limiting the onset and development of oxidative stress. These findings support the claim that curcumin as turmeric can effectively inhibit inflammatory reactions and reduces symptoms through changing the redox status. Future large randomized controlled trials on the effects of turmeric substance are needed.

Background: The impact of the SARS-CoV-2 viral infection during pregnancy on the fetus can be direct—transmitted through the placenta—and indirect—creating unfavorable conditions for the development of the fetus because of inflammation, micro-thrombosis, and hypercoagulation. Our study aimed to determine the types and frequency of pathohistological changes in placental tissue in SARS-CoV-2-positive pregnant women and to examine the possible role of oxidative stress in the prognosis of the delivery and its maternal and fetal complications. Methods: This prospective clinical study included 50 pregnant women divided into two groups, SARS-CoV-2 positive (COVID-19 group) and SARS-CoV-2 negative (control group), from who we collected demographic, clinical, obstetric, biochemical and pathologic data. Data about the newborn characteristics were also collected, which included anamnestic, clinical, and biochemical data. Results: The values of the superoxide anion radical and index of lipid peroxidation were significantly different in mothers concerning the presence of the SARS-CoV-2 infection, while the levels of the nitric oxide, index of lipid peroxidation, reduced glutathione, and superoxide dismutase were significantly different in the newborns depending on the SARS-CoV-2 infection. Newborn characteristics were similar between groups except for concentrations of IgM antibody. The incidence of pathohistological changes of the FVM type in the COVID-19 group of pregnant women was 46%, while in the control group, the incidence was 18%. Conclusions: This study confirmed the significant impact of the SARS-CoV-2 viral infection on maternal and fetal biochemical parameters and oxidative stress-mediated placental dysfunction. Future studies should be performed with more participants and follow-up neonatal development.

As several decades of research have shown the cardioprotective effects of angiotensin-converting enzyme (ACE) inhibitors alone or in combination with diuretics, we were interested in investigating the effects of subchronic therapy of these drugs on ischemia–reperfusion (I/R) damage to the heart, as well as their influence on oxidative status. The research was conducted on 40 spontaneously hypertensive male Wistar Kyoto rats, divided into 4 groups. Animals were treated for four weeks with 10 mg/kg/day zofenopril alone or in combination with hydrochlorothiazide, indapamide and spironolactone per os. After the treatment, hemodynamic measurements, echocardiography and assessment of myocardial function were performed according to Langendorff's retrograde perfusion method. The induced global ischemia model involved 20 min of ischemia followed by 30 min of reperfusion to the heart (I20:R30). Markers of oxidative stress were determined spectrophotometrically from plasma and erythrocyte lysates. Heart and kidney tissue samples were pathohistologically analyzed. Treatment with a combination of ACE inhibitors and diuretics significantly lowered blood pressure in spontaneously hypertensive rats, alleviated left ventricular hypertrophy and increased ejection fraction. On the other hand, treatment with zofenopril and diuretics showed pro-oxidative potential. Pathohistological analysis of heart and kidney tissue samples indicates that subchronic administration of antihypertensive agents does not lead to significant changes in these organs. Since the antihypertensive therapy was relatively short (only 4 weeks), in order to elucidate or deny the prooxidative mechanism, additional studies of a longer time interval are needed and planned.

Background: The impact of SARS-CoV-2 viral infection during pregnancy on the fetus can be direct, transmitted through the placenta, and indirect - creating unfavorable conditions for the development of the fetus because of inflammation, micro-thrombosis, and hypercoagulation. The Aim: Our study aimed to determine the types and frequency of pathohistological changes in placental tissue in SARS-CoV-2-positive pregnant women and to examine the possible role of oxidative stress in the prognosis of the delivery and its maternal and fetal complications. Methods: This prospective clinical study included 50 pregnant women divided into two groups, SARS-CoV-2 positive (COVID-19 group) and SARS-CoV-2 negative (Control group), from whose we collected demographic, clinical, obstetric, biochemical, and pathologic data. Data about the newborn characteristics were also collected: anamnestic, clinical, and biochemical data. Results: The values of the superoxide anion radical and index of lipid peroxidation were significantly different in mothers concerning the presence of the SARS-CoV-2 infection, while the levels of the nitric oxide, index of lipid peroxidation, reduced glutathione, and superoxide dismutase were significantly different in the newborns depending on the SARS-CoV-2 infection. Newborn characteristics were similar between groups except for concentrations of IgM antibody. The incidence of pathohistological changes of the FVM type in the COVID-19 group of pregnant women was 46%, while in the control group. Conclusions: This study confirmed the significant impact of the SARS-CoV-2 viral infection on maternal and fetal biochemical parameters and oxidative stress-mediated placental dysfunction. Future studies should be performed with more participants and follow-up neonatal development.

Polycystic ovary syndrome (PCOS) is the most common complex endocrinological condition of women that is associated with infertility and metabolic disorders during the reproductive period. Recently, a great deal of research has focused on the etiopathogenesis of this disorder and the modulation of therapeutic approaches. There are still many controversies in the choice of therapy, and metformin is one of the most commonly used agents in the treatment of PCOS. Considering the link between metabolic disorders and PCOS, glycemic status is crucial in these patients, and sodium-glucose cotransporter type 2 inhibitors (SGLT2is) represent a potentially promising new therapeutic approach. These drugs have been shown to improve glucose metabolism, reduce adipose tissue, decrease oxidative stress, and protect the cardiovascular system. These data prompted us to investigate the effects of empagliflozin (EMPA) in a PCOS rat model and compare them with the effects of metformin. We confirmed that EMPA positively affects somatometric parameters, glucose and lipid metabolism, and the levels of sex hormones, as well as reduces oxidative stress and improves ovarian function and morphology. Administration of EMPA at doses of 5 mg/kg, 15 mg/kg, and 45 mg/kg during a 4-week treatment period improved, as induced by estradiol valerate and a high-fat diet, the metabolic and reproductive statuses in a PCOS rat model. The best effects, which were comparable to the effects of metformin, were achieved in groups receiving the middle and highest applied doses of EMPA. These results may prompt further clinical research on the use of EMPA in patients with PCOS.

Oxidative stress represents the pathophysiological basis for most disorders, including reproductive issues. Polycystic ovary syndrome (PCOS) is heterogeneous endocrine disorder of women characterized primarily by irregular menstrual cycles, hyper-androgenism, and ovulatory dysfunction. In the last decades, PCOS was recognized as a systemic silent inflammation and an oxidative disturbance-related disorder, exerting multifaceted symptoms, including metabolic. PCOS treatment should involve a personalized approach tailored to individual symptoms; however, the results are often unsatisfactory. Various supplementary treatments have been proposed to assist in the management and alleviation of PCOS symptoms. Cinnamon and ginger, known for millennia as herbs used in spices or traditional medicine for the treatment of various diseases, are of interest in this study. The aim of this study is to evaluate and investigate the effects of cinnamon and ginger in PCOS patients. Using relevant keywords we searched through PubMed/MEDLINE, Science Direct, Google Scholar and Web of science to find animal studies, pre-clinical, and clinical studies which were then reviewed for usage. Out of all of the reviewed studies a total of 65 studies were included in this review article. Cinnamon and ginger can affect hormonal status, lipid profile, obesity, and insulin resistance by mitigating oxidative stress and inflammation. Generally, based on current clinical evidence, it was revealed that supplementation with cinnamon or ginger had a useful impact in patients with PCOS. This review summarizes the antioxidative effects of ginger and cinnamon in PCOS treatment, highlighting their potential benefits in other oxidative stress-related pathologies.