Joint Cardioprotective Effect of Vitamin C and Other Antioxidants against Reperfusion Injury in Patients with Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

Percutaneous coronary intervention (PCI) has long remained the gold standard therapy to restore coronary blood flow after acute myocardial infarction (AMI). However, this procedure leads to the development of increased production of reactive oxygen species (ROS) that can exacerbate the damage caused by AMI, particularly during the reperfusion phase. Numerous attempts based on antioxidant treatments, aimed to reduce the oxidative injury of cardiac tissue, have failed in achieving an effective therapy for these patients. Among these studies, results derived from the use of vitamin C (Vit C) have been inconclusive so far, likely due to suboptimal study designs, misinterpretations, and the erroneous conclusions of clinical trials. Nevertheless, recent clinical trials have shown that the intravenous infusion of Vit C prior to PCI-reduced cardiac injury biomarkers, as well as inflammatory biomarkers and ROS production. In addition, improvements of functional parameters, such as left ventricular ejection fraction (LVEF) and telediastolic left ventricular volume, showed a trend but had an inconclusive association with Vit C. Therefore, it seems reasonable that these beneficial effects could be further enhanced by the association with other antioxidant agents. Indeed, the complexity and the multifactorial nature of the mechanism of injury occurring in AMI demands multitarget agents to reach an enhancement of the expected cardioprotection, a paradigm needing to be demonstrated. The present review provides data supporting the view that an intravenous infusion containing combined safe antioxidants could be a suitable strategy to reduce cardiac injury, thus improving the clinical outcome, life quality, and life expectancy of patients subjected to PCI following AMI.

Exploring Neuroprotection against Radiation-Induced Brain Injury: A Review of Key Compounds.

Brain radiation is a crucial tool in neuro-oncology for enhancing local tumor control, but it can lead to mild-to-profound and progressive impairments in cognitive function. Radiation-induced brain injury is a significant adverse effect of radiotherapy for cranioencephalic tumors, primarily caused by indirect cellular damage through the formation of free radicals. This results in late neurotoxicity manifesting as cognitive impairment due to free radical production. The aim of this review is to highlight the role of different substances, such as drugs used in the clinical setting and antioxidants such as ascorbate, in reducing the neurotoxicity associated with radiation-induced brain injury. Currently, there is mainly preclinical and clinical evidence supporting the benefit of these interventions, representing a cost-effective and straightforward neuroprotective strategy.

Integrated approach to reducing polypharmacy in older people: exploring the role of oxidative stress and antioxidant potential therapy.

Increased life expectancy, attributed to improved access to healthcare and drug development, has led to an increase in multimorbidity, a key contributor to polypharmacy. Polypharmacy is characterised by its association with a variety of adverse events in the older persons. The mechanisms involved in the development of age-related chronic diseases are largely unknown; however, altered redox homeostasis due to ageing is one of the main theories. In this context, the present review explores the development and interaction between different age-related diseases, mainly linked by oxidative stress. In addition, drug interactions in the treatment of various diseases are described, emphasising that the holistic management of older people and their pathologies should prevail over the individual treatment of each condition.

Tapping into Nature's Arsenal: Harnessing the Potential of Natural Antioxidants for Human Health and Disease Prevention.

Numerous natural antioxidants commonly found in our daily diet have demonstrated significant benefits for human health and various diseases by counteracting the impact of reactive oxygen and nitrogen species. Their chemical properties enable a range of biological actions, including antihypertensive, antimicrobial, anti-inflammatory, anti-fibrotic, and anticancer effects. Despite promising outcomes from preclinical studies, ongoing debate persists regarding their reproducibility in human clinical models. This controversy largely stems from a lack of understanding of the pharmacokinetic properties of these compounds, coupled with the predominant focus on monotherapies in research, neglecting potential synergistic effects arising from combining different antioxidants. This study aims to provide an updated overview of natural antioxidants, operating under the hypothesis that a multitherapeutic approach surpasses monotherapy in efficacy. Additionally, this study underscores the importance of integrating these antioxidants into the daily diet, as they have the potential to prevent the onset and progression of various diseases. To reinforce this perspective, clinical findings pertaining to the treatment and prevention of non-alcoholic fatty liver disease and conditions associated with ischemia and reperfusion phenomena, including myocardial infarction, postoperative atrial fibrillation, and stroke, are presented as key references.

Antioxidant Protection against Trastuzumab Cardiotoxicity in Breast Cancer Therapy.

Breast cancer is the most frequent malignant neoplastic disease in women, with an estimated 2.3 million cases in 2020 worldwide. Its treatment depends on characteristics of the patient and the tumor. In the latter, characteristics include cell type and morphology, anatomical location, and immunophenotype. Concerning this latter aspect, the overexpression of the HER2 receptor, expressed in 15-25% of tumors, is associated with greater aggressiveness and worse prognosis. In recent times some monoclonal antibodies have been developed in order to target HER2 receptor overexpression. Trastuzumab is part of the monoclonal antibodies used as targeted therapy against HER2 receptor, whose major problem is its cardiac safety profile, where it has been associated with cardiotoxicity. The appearance of cardiotoxicity is an indication to stop therapy. Although the pathophysiological mechanism is poorly known, evidence indicates that oxidative stress plays a fundamental role causing DNA damage, increased cytosolic and mitochondrial ROS production, changes in mitochondrial membrane potential, intracellular calcium dysregulation, and the consequent cell death through different pathways. The aim of this review was to explore the use of antioxidants as adjuvant therapy to trastuzumab to prevent its cardiac toxicity, thus leading to ameliorate its safety profile in its administration.

Targeting Ferroptosis against Ischemia/Reperfusion Cardiac Injury.

Ischemic heart disease is a leading cause of death worldwide. Primarily, ischemia causes decreased oxygen supply, resulting in damage of the cardiac tissue. Naturally, reoxygenation has been recognized as the treatment of choice to recover blood flow through primary percutaneous coronary intervention. This treatment is the gold standard therapy to restore blood flow, but paradoxically it can also induce tissue injury. A number of different studies in animal models of acute myocardial infarction (AMI) suggest that ischemia-reperfusion injury (IRI) accounts for up to 50% of the final myocardial infarct size. Oxidative stress plays a critical role in the pathological process. Iron is an essential mineral required for a variety of vital biological functions but also has potentially toxic effects. A detrimental process induced by free iron is ferroptosis, a non-apoptotic type of programmed cell death. Accordingly, efforts to prevent ferroptosis in pathological settings have focused on the use of radical trapping antioxidants (RTAs), such as liproxstatin-1 (Lip-1). Hence, it is necessary to develop novel strategies to prevent cardiac IRI, thus improving the clinical outcome in patients with ischemic heart disease. The present review analyses the role of ferroptosis inhibition to prevent heart IRI, with special reference to Lip-1 as a promising drug in this clinicopathological context.