Oxygen administration is particularly relevant in patients undergoing surgery under general anesthesia and in those who suffer from acute or critical illness. Nevertheless, excess O2, or hyperoxia, is also known to be harmful. Toxicity arises from the enhanced formation of Reactive Oxygen Species (ROS) that, exceeding the antioxidant defense, may generate oxidative stress. Oxidative stress markers are used to quantify ROS toxicity in clinical and non-clinical settings and represent a promising tool to assess the optimal FiO2 in anesthesia and critical care setting. Despite controversial, the guidelines for the regulation of FiO2 in such settings suggest the adoption of high perioperative oxygen levels. However, hyperoxia has also been shown to be an independent mortality risk factor in critically ill patients. In this literature review, we discuss the biochemical mechanisms behind oxidative stress and the available biomarkers for assessing the pro-oxidant vs antioxidant status. Then, we summarize recent knowledge on the hyperoxia-related consequences in the most common anesthesia and critical care settings, such as traumatic brain injury or cardiac arrest. To this purpose, we searched the Pubmed database according to the following combination of key words: ("hyperoxia" OR "FiO2" OR "oxygen therapy") AND ("oxidative stress" OR "ROS" OR "RNS" OR "lipid peroxidation") AND ("anesthesia" OR "surgery" OR "intensive care"). We focused in the results from the past 20 years. Available evidence points toward a conservative monitoring and use of oxygen, unless there is solid proof of its efficacy.

Natural dietary components are evolutionary-selected molecules able to control inflammation and cancerous transformation and progression. Because many studies assessed the beneficial properties of key molecules extracted from grapes, we aimed at investigating the properties of Liofenol™, a natural red wine lyophilized extract, devoid of alcohol and composed by a miscellaneous of components (polyphenols, flavonoids, anthocyanins). We proved that the colon cancer cell line HCT116 responded to Liofenol™ treatment by reducing their proliferation, in association with an increase of p53 and p21 cell cycle gate keepers. Liofenol™ increased dihydroceramides, sphingolipid mediators involved in cell cycle arrest and reduced proliferation rate. We observed a strong induction of antioxidant response, with the activation of the transcriptional factor Nrf2, involved in redox homeostasis and differentiation, without altering tumor sensitivity to chemotherapy. Liofenol™ induced an important morphology change in HCT116 cells, migration inhibition, undifferentiated stem/stem-like cells markers downregulation, and E-cadherin downregulation, interested in epithelia to mesenchymal malignant transition. We conclude that lyophilized grape extract, at dose comparable to putative dietary doses, can activate molecular pathways, involving Nrf2 signaling and the modulation of structural and signaling sphingolipid mediators that cooperate in promoting differentiation and reducing proliferation of digestive tract cancer cells.

BackgroundSeveral mechanisms allow humans to resist the extreme conditions encountered during breath-hold diving. Available nitric oxide (NO) is one of the major contributors to such complex adaptations at depth and oxidative stress is one of the major collateral effects of diving. Due to technical difficulties, these biomarkers have not so far been studied in vivo while at depth. The aim of this study is to investigate nitrate and nitrite (NOx) concentration, total antioxidant capacity (TAC) and lipid peroxidation (TBARS) before, during, and after repetitive breath-hold dives in healthy volunteers.Materials and MethodsBlood plasma, obtained from 14 expert breath-hold divers, was tested for differences in NOx, TAC, and TBARS between pre-dive, bottom, surface, 30 and 60 min post-dive samples.ResultsWe observed a statistically significant increase of NOx plasma concentration in the “bottom blood draw” as compared to the pre-dive condition while we did not find any difference in the following samples We found a statistically significant decrease in TAC at the bottom but the value returned to normality immediately after reaching the surface. We did not find any statistically significant difference in TBARS.DiscussionThe increased plasma NOx values found at the bottom were not observed at surface and post dive sampling (T0, T30, T60), showing a very rapid return to the pre-dive values. Also TAC values returned to pre- diving levels immediately after the end of hyperbaric exposure, probably as a consequence of the activation of endogenous antioxidant defenses. TBARS did not show any difference during the protocol.

Introduction: Nitric oxide (NO) plays an important role in the physiology and pathophysiology of diving, and the related endothelial dysfunction and oxidative stress roles have been extensively investigated. However, most available data have been obtained before and after the dive, whilst, as far as we know, no data is available about what happens during the water immersion phase of dive. The scope of this study is to investigate the Nitrate and Nitrite (NO X ) concentration and the total plasma antioxidant capacity (TAC) before, during and after a single SCUBA dive in healthy scuba diving volunteers, as well as to look for evidence of a possible relationship with venous gas bubble formation. Materials and Methods: Plasma, obtained from blood of 15 expert SCUBA divers, 13 male and 2 female, was investigated for differences in NO X and TAC values in different dive times. Differences in NO X and TAC values in subjects previously known as “bubble resistant” (non-bubblers – NB) and “bubble prone” (Bubblers – B) were investigated. Results: We found a statistically significant increase of NO X plasma concentration in the “bottom blood draw” and in the “safety stop blood draw” as compared to the basal pre diving condition. We did not find any difference in NO X plasma concentration between the basal value and the post diving samples. We did not find any significant statistical difference in TAC in the bottom blood sample, while the safety-stop and the post-dive samples showed higher TAC values compared with the basal value. We did not find any difference in NO X and TAC mean values between non-bubblers and Bubblers. Discussion: Our protocol, by including underwater blood drawing, allowed to monitor plasma NO X changes occurred during diving activity, and not only by comparing pre and post diving values. It is particularly interesting to note that the increased NO X values found at the bottom and at the safety stop were not observed at post dive sampling (T0, T30, T60), showing a very rapid return to the pre-dive values. In this preliminary study we did not find any relationship between bubble formation and changes in NO X parameters and TAC response.

Exposure to cigarette smoke represents the most important risk factor for the development of chronic obstructive pulmonary disease (COPD). COPD is characterized by chronic inflammation of the airways, imbalance of proteolytic activity resulting in the destruction of lung parenchyma, alveolar hypoxia, oxidative stress, and apoptosis. Sphingolipids are structural membrane components whose metabolism is altered during stress. Known as apoptosis and inflammation inducer, the sphingolipid ceramide was found to accumulate in COPD airways and its plasma concentration increased as well. The present study investigates the role of sphingolipids in the cigarette smoke-induced damage of human airway epithelial cells. Lung epithelial cells were pre-treated with sphingolipid synthesis inhibitors (myriocin or XM462) and then exposed to a mixture of nicotine, acrolein, formaldehyde, and acetaldehyde, the major toxic cigarette smoke components. The inflammatory and proteolytic responses were investigated by analysis of the mRNA expression (RT-PCR) of cytokines IL-1β and IL-8, and matrix metalloproteinase-9 and of the protein expression (ELISA) of IL-8. Ceramide intracellular amounts were measured by LC-MS technique. Ferric-reducing antioxidant power test and superoxide anion radical scavenging activity assay were used to assess the antioxidant power of the inhibitors of ceramide synthesis. We here show that ceramide synthesis is enhanced under treatment with a cigarette smoke mixture correlating with increased expression of inflammatory cytokines and matrix metalloproteinase 9. The use of inhibitors of ceramide synthesis protected from smoke induced damages such as inflammation, oxidative stress, and proteolytic imbalance in airways epithelia.

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Freeskiing is performed in an extreme environment, with significant physical effort that can induce reactive oxygen species (ROS) generation and dehydration. This study aimed to investigate the evolution of the oxy-inflammation and hydration status during a freeskiing training season with non-invasive methods. Eight trained freeskiers were investigated during a season training: T0 (beginning), T1-T3 (training sessions), and T4 (after the end). Urine and saliva were collected at T0, before (A) and after (B) T1-T3, and at T4. ROS, total antioxidant capacity (TAC), interleukin-6 (IL-6), nitric oxide (NO) derivatives, neopterin, and electrolyte balance changes were investigated. We found significant increases in ROS generation (T1A-B +71%; T2A-B +65%; T3A-B +49%; p < 0.05–0.01) and IL-6 (T2A-B +112%; T3A-B +133%; p < 0.01). We did not observe significant variation of TAC and NOx after training sessions. Furthermore, ROS and IL-6 showed statistically significant differences between T0 and T4 (ROS + 48%, IL-6 + 86%; p < 0.05). Freeskiing induced an increase in ROS production, which can be contained by antioxidant defense activation, and in IL-6, as a consequence of physical activity and skeletal muscular contraction. We did not find deep changes in electrolytes balance, likely because all freeskiers were well-trained and very experienced.

The metabolism of nitric oxide plays an increasingly interesting role in the physiological response of the human body to extreme environmental conditions, such as underwater, in an extremely cold climate, and at low oxygen concentrations. Field studies need the development of analytical methods to measure nitrite and nitrate in plasma and red blood cells with high requirements of accuracy, precision, and sensitivity. An optimized spectrophotometric Griess method for nitrite–nitrate affords sensitivity in the low millimolar range and precision within ±2 μM for both nitrite and nitrate, requiring 100 μL of scarcely available plasma sample or less than 50 μL of red blood cells. A scheduled time-efficient procedure affords measurement of as many as 80 blood samples, with combined nitrite and nitrate measurement in plasma and red blood cells. Performance and usefulness were tested in pilot studies that use blood fractions deriving from subjects who dwelt in an Antarctica scientific station and on breath-holding and scuba divers who performed training at sea and in a land-based deep pool facility. The method demonstrated adequate to measure low basal concentrations of nitrite and high production of nitrate as a consequence of water column pressure-triggered vasodilatation in deep-water divers.