Reactive oxygen species (ROS) are important molecules in the living organisms as a part of many signaling pathways. However, if overproduced, they also play a significant role in the development of cardiovascular diseases, such as arrhythmia, cardiomyopathy, ischemia/reperfusion injury (e.g., myocardial infarction and heart transplantation), and heart failure. As a result of oxidative stress action, apoptosis, hypertrophy, and fibrosis may occur. MicroRNAs (miRNAs) represent important endogenous nucleotides that regulate many biological processes, including those involved in heart damage caused by oxidative stress. Oxidative stress can alter the expression level of many miRNAs. These changes in miRNA expression occur mainly via modulation of nuclear factor erythroid 2-related factor 2 (Nrf2), sirtuins, calcineurin/nuclear factor of activated T cell (NFAT), or nuclear factor kappa B (NF-κB) pathways. Up until now, several circulating miRNAs have been reported to be potential biomarkers of ROS-related cardiac diseases, including myocardial infarction, hypertrophy, ischemia/reperfusion, and heart failure, such as miRNA-499, miRNA-199, miRNA-21, miRNA-144, miRNA-208a, miRNA-34a, etc. On the other hand, a lot of studies are aimed at using miRNAs for therapeutic purposes. This review points to the need for studying the role of redox-sensitive miRNAs, to identify more effective biomarkers and develop better therapeutic targets for oxidative-stress-related heart diseases.

Omega-3 polyunsaturated fatty acids (PUFAs), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are permanent subjects of interest in relation to the protection of cardiovascular health and the prevention of the incidence of both ventricular and atrial arrhythmias. The purpose of this updated review is to focus on the novel cellular and molecular effects of omega-3 PUFAs, in the context of the mechanisms and factors involved in the development of cardiac arrhythmias; to provide results of the most recent studies on the omega-3 PUFA anti-arrhythmic efficacy and to discuss the lack of the benefit in relation to omega-3 PUFA status. The evidence is in the favor of omega-3 PUFA acute and long-term treatment, perhaps with mitochondria-targeted antioxidants. However, for a more objective evaluation of the anti-arrhythmic potential of omega-3 PUFAs in clinical trials, it is necessary to monitor the basal pre-interventional omega-3 status of individuals, i.e., red blood cell content, omega-3 index and free plasma levels. In the view of evidence-based medicine, it seems to be crucial to aim to establish new approaches in the prevention of cardiac arrhythmias and associated morbidity and mortality that comes with these conditions.

Irradiation of normal tissues leads to acute increase in reactive oxygen/nitrogen species that serve as intra- and inter-cellular signaling to alter cell and tissue function. In the case of chest irradiation, it can affect the heart, blood vessels, and lungs, with consequent tissue remodelation and adverse side effects and symptoms. This complex process is orchestrated by a large number of interacting molecular signals, including cytokines, chemokines, and growth factors. Inflammation, endothelial cell dysfunction, thrombogenesis, organ dysfunction, and ultimate failing of the heart occur as a pathological entity — “radiation-induced heart disease” (RIHD) that is major source of morbidity and mortality. The purpose of this review is to bring insights into the basic mechanisms of RIHD that may lead to the identification of targets for intervention in the radiotherapy side effect. Studies of authors also provide knowledge about how to select targeted drugs or biological molecules to modify the progression of radiation damage in the heart. New prospective studies are needed to validate that assessed factors and changes are useful as early markers of cardiac damage.

The prevention of cardiac life-threatening ventricular fibrillation and stroke-provoking atrial fibrillation remains a serious global clinical issue, with ongoing need for novel approaches. Numerous experimental and clinical studies suggest that oxidative stress and inflammation are deleterious to cardiovascular health, and can increase heart susceptibility to arrhythmias. It is quite interesting, however, that various cardio-protective compounds with antiarrhythmic properties are potent anti-oxidative and anti-inflammatory agents. These most likely target the pro-arrhythmia primary mechanisms. This review and literature-based analysis presents a realistic view of antiarrhythmic efficacy and the molecular mechanisms of current pharmaceuticals in clinical use. These include the sodium-glucose cotransporter-2 inhibitors used in diabetes treatment, statins in dyslipidemia and naturally protective omega-3 fatty acids. This approach supports the hypothesis that prevention or attenuation of oxidative and inflammatory stress can abolish pro-arrhythmic factors and the development of an arrhythmia substrate. This could prove a powerful tool of reducing cardiac arrhythmia burden.

Cardiac connexin-43 (Cx43) creates gap junction channels (GJCs) at intercellular contacts and hemi-channels (HCs) at the peri-junctional plasma membrane and sarcolemmal caveolae/rafts compartments. GJCs are fundamental for the direct cardiac cell-to-cell transmission of electrical and molecular signals which ensures synchronous myocardial contraction. The HCs and structurally similar pannexin1 (Panx1) channels are active in stressful conditions. These channels are essential for paracrine and autocrine communication through the release of ions and signaling molecules to the extracellular environment, or for uptake from it. The HCs and Panx1 channel-opening profoundly affects intracellular ionic homeostasis and redox status and facilitates via purinergic signaling pro-inflammatory and pro-fibrotic processes. These conditions promote cardiac arrhythmogenesis due to the impairment of the GJCs and selective ion channel function. Crosstalk between GJCs and HCs/Panx1 channels could be crucial in the development of arrhythmogenic substrates, including fibrosis. Despite the knowledge gap in the regulation of these channels, current evidence indicates that HCs and Panx1 channel activation can enhance the risk of cardiac arrhythmias. It is extremely challenging to target HCs and Panx1 channels by inhibitory agents to hamper development of cardiac rhythm disorders. Progress in this field may contribute to novel therapeutic approaches for patients prone to develop atrial or ventricular fibrillation.

Non-alcoholic fatty liver disease (NAFLD) is a liver pathology affecting around 25% of the population worldwide. Excess oxidative stress, inflammation and aberrant cellular signaling can lead to this hepatic dysfunction and eventual carcinoma. Molecular hydrogen has been recognized for its selective antioxidant properties and ability to attenuate inflammation and regulate cellular function. We administered hydrogen-rich water (HRW) to 30 subjects with NAFLD in a randomized, double-blinded, placebo-controlled manner for eight weeks. Phenotypically, we observed beneficial trends (p > 0.05) in decreased weight (≈1 kg) and body mass index in the HRW group. HRW was well-tolerated, with no significant changes in liver enzymes and a trend of improved lipid profile and reduced lactate dehydrogenase levels. HRW tended to non-significantly decrease levels of nuclear factor kappa B, heat shock protein 70 and matrix metalloproteinase-9. Interestingly, there was a mild, albeit non-significant, tendency of increased levels of 8-hydroxy-2’-deoxyguanosine and malondialdehyde in the HRW group. This mild increase may be indicative of the hormetic effects of molecular hydrogen that occurred prior to the significant clinical improvements reported in previous longer-term studies. The favorable trends in this study in conjunction with previous animal and clinical findings suggest that HRW may serve as an important adjuvant therapy for promoting and maintaining optimal health and wellness. Longer term studies focused on prevention, maintenance, or treatment of NAFLD and early stages of NASH are warranted.