Adaptation to oxidative stress at cellular and tissue level.

Several in vitro and in vivo investigations have already proved that cells and tissues, when pre-exposed to low oxidative stress by different stimuli such as chemical, physical agents and environmental factors, display more resistance against subsequent stronger ischaemic injuries, resulting in an adaptive response known as ischaemic preconditioning (IPC). The aim of this review is to report the most recent knowledge about the complex adaptive mechanisms, including signalling transduction pathways, antioxidant systems, apoptotic and inflammation pathways, underlying cell protection against oxidative damage. In addition, an update about in vivo adaptation strategies in response to ischaemic/reperfusion episodes and brain trauma is also given.

Potentiality of ghrelin as antioxidant and protective agent.

BACKGROUND: Oxidative stress is the result of cellular troubles related to aerobic metabolism. Furthermore, this stress is always associated with biological responses evoked by physical, chemical, environmental, and psychological factors. Several studies have developed many approaches of antioxidant defense to diminish the severity of many diseases. Ghrelin was originally identified from the rat stomach, and it is a potent growth hormone-releasing peptide that has pleiotropic functions. METHODS: A systematic review was conducted within PubMed, ScienceDirect, MEDLINE, and Scopus databases using keywords such as ghrelin, antioxidant, oxidative stress, and systemic oxidative stress sensor. RESULTS: In the last decade, many studies show that ghrelin exhibits protection effects against oxidative stress derived probably from its antioxidant effects. Pieces of evidence demonstrate that systemic oxidative stress increase ghrelin levels in the plasma. The expression of ghrelin and its receptor in ghrelin peripheral tissues and extensively in the central nervous system suggests that this endogenous peptide plays an important role as a systemic oxidative stress sensor. CONCLUSION: The current evidence confirms that ghrelin and its derived peptides (Desacyl-ghrelin, obestatin) act as a protective antioxidant agent. Therefore, stressor modality, duration, and intensity are the parameters of oxidative stress that must be taken into consideration to determine the role of ghrelin, Desacyl-ghrelin, and obestatin in the regulation of cell death pathways.

COVID-19: Oxidative Preconditioning as a Potential Therapeutic Approach.

This Article summarizes the likely benefits of central nervous system oxidative preconditioning in the reduction of COVID-19 based on its putative pathogenesis. The current COVID-19 outbreak caused a pandemic with millions of infected patients and death cases worldwide. The clinical features of severe acute respiratory syndrome coronavirus (SARS-CoV) was initially linked with respiratory disorders, but recent studies have reported alterations of neurological and cerebrovascular functions in COVID-19 patients. The main viral infection features are related to cell death, inflammation, and cytokine generation, which can be associated with the dysregulation of redox systems or oxidative stress. However, until now, there is no available and effective therapeutic approach. Thus, it is necessary to search for care and adequate protection against the disease, especially for susceptible and vulnerable groups. Preconditioning, a well-known antioxidative stress and anti-inflammatory approach, is protective against many neurological age-related disorders. COVID-19 severity and morbidity have been observed in elderly patients. The aim of the present study is to elucidate the possible protective role of oxidative preconditioning in aged patients at high risk of developing severe COVID-19 complications.

Neuronal-like differentiated SH-SY5Y cells adaptation to a mild and transient H2 O2 -induced oxidative stress.

Preconditioning (PC) is a cell adaptive response to oxidative stress and, with regard to neurons, can be considered as a neuroprotective strategy. The aim of the present study was to verify how neuronal-like differentiated SH-SY5Y cells adapt to a mild and transient H2 O2 -induced oxidative stress and, hence, whether may be considered as more sensitive cell model to study PC pathways. A first screening allowed to define H2 O2 concentrations for PC (10µM-50µM), applied before damage(100µM H2 O2 ). Cell viability measured 24 hours after 100µM H2 O2 -induced damage was ameliorated by 24-hour pre-exposure to low-concentration H2 O2 (10µM-30µM) with cell size as well restored. Markers for apoptosis (Bcl-2 and Bad), inflammation (iNOS), and redox system (MnSOD) were also determined, showing that, in cells pre-exposed to 10µM H2 O2 and then submitted to 100µM H2 O2 , Bcl-2 levels were higher, Bad and iNOS levels were lower than those observed in damaged cells, and MnSOD levels were unchanged. Such findings show that (1) neuronal-like differentiated SH-SY5Y cells are a suitable model to investigate PC response and more sensitive to the effect of a mild and transient H2 O2 -induced oxidative stress with respect to other neuronal cells; (2) 10µM H2 O2 -induced PC is mediated by apoptotic and inflammatory pathways, unlike antioxidant system; (3) such neuroprotective strategy and underlying signals proven in neuronal-like differentiated SH-SY5Y cells may contribute to understand in vivo PC mechanisms and to define a window for pharmacological intervention, namely, related to ischemic brain damage. SIGNIFICANCE OF THE STUDY: Neuronal-like differentiated SH-SY5Y cells are a suitable model to investigate PC, an endogenous neuroprotective response to a mild and transient H2 O2 -induced oxidative stress, elicited by 24-hour exposure to very low H2 O2 concentrations and mediated by both apoptotic and inflammatory pathways. This model reflects in vivo PC mechanisms occurring after brain trauma and provides novel information about pathways and time of protection useful for an appropriate pharmacological intervention.