1,721,005 research outputs found

    DNA alterations in rat organs after chronic exposure to cigarette smoke and/or ethanol ingestion

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    In spite of the epidemiological evidence supporting a synergism between alcohol consumption and cigarette smoking in the pathogenesis of cancers of the aerodigestive tract, there is a paucity of experimental studies evaluating the effects of these agents under well-controlled conditions and exploring the mechanisms involved. We exposed groups of female BD rats, aged 8 months, to ethanol (5% in drinking water for 8 consecutive months) and/or whole-body to mainstream cigarette smoke (1 h/day, 5 days/week for 8 months). DNA was purified from different organs and analyzed for the presence of DNA- protein crosslinks and 32P-postlabeled DNA adducts after butanol enrichment. No significant increase of DNA-protein crosslinks, compared to untreated controls, was induced by any treatment in liver, lung, or heart. 'Spontaneous' nucleotidic modifications were detected by 32p-postlabeling in organs of untreated rats, with the highest levels occurring in the heart. Ingestion of ethanol did not affect DNA adduct levels in any of the organs examined: esophagus, liver, lung, and heart. Exposure to cigarette smoke induced formation of DNA adducts in the lung and heart, but not in the esophagus or liver. The combined ingestion of ethanol resulted in a significant formation of smoke-related DNA adducts in the esophagus and in their further, dramatic increase in the heart. It thus appears that ethanol consumption increases the bioavailability of DNA binding smoke components in the upper digestive tract and favors their systemic distribution. The mechanisms responsible for the interaction between ethanol and smoke and for the selective localization of DNA alterations in different organs are discussed. Formation of DNA adducts in the organs examined may be relevant in the pathogenesis of lung and esophageal cancers as well as in the pathogenesis of other types of chronic degenerative diseases, such as chronic obstructive pulmonary diseases and cardiomyopathies. - Izzotti, A., Balansky, R. M., Blagoeva, P.M., Mircheva, Z.I., Tulimiero, L., Cartiglia, C., De Flora, S. DNA alterations in rat organs after chronic exposure to cigarette smoke and/or ethanol ingestion

    Rationale for the use of N-acetylcysteine in both prevention and adjuvant therapy of COVID-19

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    COVID-19 may cause pneumonia, acute respiratory distress syndrome, cardiovascular alterations, and multiple organ failure, which have been ascribed to a cytokine storm, a systemic inflammatory response, and an attack by the immune system. Moreover, an oxidative stress imbalance has been demonstrated to occur in COVID-19 patients. N- Acetyl-L-cysteine (NAC) is a precursor of reduced glutathione (GSH). Due to its tolerability, this pleiotropic drug has been proposed not only as a mucolytic agent, but also as a preventive/therapeutic agent in a variety of disorders involving GSH depletion and oxidative stress. At very high doses, NAC is also used as an antidote against paracetamol intoxication. Thiols block the angiotensin-converting enzyme 2 thereby hampering penetration of SARS-CoV-2 into cells. Based on a broad range of antioxidant and anti-inflammatory mechanisms, which are herein reviewed, the oral administration of NAC is likely to attenuate the risk of developing COVID-19, as it was previously demonstrated for influenza and influenza-like illnesses. Moreover, high-dose intravenous NAC may be expected to play an adjuvant role in the treatment of severe COVID-19 cases and in the control of its lethal complications, also including pulmonary and cardiovascular adverse events
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