Coenzyme Q10 Alleviates Chronic Nucleoside Reverse Transcriptase Inhibitor-Induced Premature Endothelial Senescence.

Human immunodeficiency virus (HIV)-infected patients undergoing antiretroviral therapy are afforded an increased lifespan but also exhibit an elevated incidence of cardiovascular disease. HIV therapy uses a combination drug approach, and nucleoside reverse transcriptase inhibitors (NRTI) are a backbone of this therapy. Endothelial dysfunction is an initiating event in cardiovascular disease etiology, and in our prior studies, NRTIs induced an endothelial dysfunction that was dependent upon mitochondrial oxidative stress.

Overexpression of mitochondrial antioxidant manganese superoxide dismutase (MnSOD) provides protection against AZT- or 3TC-induced endothelial dysfunction.

Nucleoside reverse transcriptase inhibitors (NRTIs) are considered the backbone of current combination therapies for HIV. These therapies have significantly decreased mortality and morbidity in HIV-infected patients, but some are associated with cardiovascular complications, including endothelial dysfunction, an early marker for atherosclerosis. Our prior studies demonstrated that co-treatment of cells with an antioxidant therapy reversed NRTI-induced endothelial injury.

Nucleoside reverse transcriptase inhibitors induce a mitophagy-associated endothelial cytotoxicity that is reversed by coenzyme Q10 cotreatment.

Cardiovascular complications have been documented in HIV-1 infected populations, and antiretroviral therapy may play a role. Nucleoside reverse transcriptase inhibitors (NRTIs) are antiretrovirals known to induce mitochondrial damage in endothelial cells, culminating in endothelial dysfunction, an initiating event in atherogenesis. Though the mechanism for NRTI-induced endothelial toxicity is not yet clear, our prior work suggested that a mitochondrial oxidative stress may be involved.

The role of glucocorticoids in the immediate vs. delayed effects of acute ethanol exposure on cytokine production in a binge drinking model.

Background: Acute ethanol administration just prior to a stimulus, such as the viral mimic poly I:C, results in decreased proinflammatory cytokine production. Studies have indicated that this suppression is not primarily mediated by glucocorticoids (corticosterone in mice) released in the ethanol-induced stress response. Fewer studies have been done on the effects of acute ethanol administration 12 or more hours prior to a stimulus.

Innate immunity and inflammation in sepsis: mechanisms of suppressed host resistance in mice treated with ethanol in a binge-drinking model.

Sepsis is a major cause of mortality worldwide. Acute or chonic ethanol exposure typically suppresses innate immunity and inflammation and increases the risk of mortality in patients with sepsis. The study described here was designed to address the mechanism(s) by which acute ethanol exposure alters the course of sepsis.

The role of stress mediators in modulation of cytokine production by ethanol.

Acute ethanol exposure in humans and in animal models activates the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS); the resultant increases in concentration of neuroendocrine mediators contribute to some of the immunosuppressive effects of ethanol. However, the role of these mediators in the ethanol-induced inhibition of inflammatory responses is not clear. This is complicated by the fact that most inflammatory stimuli also activate the HPA axis and SNS, and it has not been determined if ethanol plus an inflammatory stimulus increases these stress responses.

Role of corticosterone in immunosuppressive effects of acute ethanol exposure on Toll-like receptor mediated cytokine production.

Acute ethanol (EtOH) exposure causes a stress response in humans, nonhuman primates, and rodents. Previous study results indicate that the suppression of some immunological parameters by EtOH is mediated in part or completely by elevated corticosterone concentrations induced by EtOH. However, initial results suggested that corticosterone is not involved in the modulation of cytokine production by macrophages in response to polyinosinic polycytidylic acid (poly I:C).