8-hydroxy-2--deoxyguanosine and Hemorrhage

Cardiac dysfunction (CD) has emerged as a key contributor to delayed organ failure and late mortality in patients surviving the initial traumatic hemorrhagic response. Inflammatory processes are implicated in the initial stages of this CD; however, downstream pathways leading to a characteristic rapid fall in stroke volume and cardiac output are not yet fully defined. Currently, no cardioprotective treatments are available. We investigated the role of myocardial oxidative stress in the pathogenesis of CD associated to traumatic hemorrhagic injury, and its related metabolomic profile.. Ex vivo tissue from a 3-hour murine model of pressure-controlled trauma hemorrhagic shock (THS) was analyzed. Animals were randomized to echocardiography-guided crystalloid fluid resuscitation or a control group (sham: cannulation and anesthesia only, or naïve: no intervention). Trauma hemorrhagic shock and naïve samples were assessed by immunohistochemistry for nuclear 8-hydroxy-2'-deoxyguanosine expression as a marker of oxidative stress. Metabolomic analysis of THS and sham group tissue was performed by LC-MS.. 8-Hydroxy-2'-deoxyguanosine expression across the myocardium was significantly higher following THS injury compared to naïve group (33.01 ± 14.40% vs. 15.08 ± 3.96%, p < 0.05). Trauma hemorrhagic shock injury significantly increased lysine ( p = 0.022), and decreased aconitate ( p = 0.016) and glutamate ( p = 0.047) in the myocardium, indicating activation of a catabolic metabolism and oxidative stress response.. We confirm the acute development of oxidative stress lesions and altered cardiac energy metabolism following traumatic hemorrhage injury, providing insight into the relationship between inflammatory damage and impaired cardiac contractility. These findings may provide targets for development of novel cardioprotective therapeutics aiming to decrease late mortality from trauma.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Crush Injuries; Heart; Hemorrhage; Humans; Mice; Myocardium; Shock, Hemorrhagic

In fatalities with multiple traumatic injuries, it is important to determine the severity of trauma, the main damaged organ, and the antemortem pathophysiological condition. We examined 63 cases within 48 h of the postmortem interval, which included assaults, slips and falls and falls from heights, traffic accidents, and sharp instrumental injuries. Immunohistochemically, each kidney was stained against hemoglobin (Hb), myoglobin (Mb), superoxide dismutase (SOD), 8-hydroxy-2'-deoxyguanosine (8-OHdG), 150 kDa oxygen regulated protein (ORP150), pulmonary surfactant A (SP-A), and liver-type fatty acid binding protein (L-FABP). Bleeding or circulatory failure induced ORP150, 8-OHdG, and L-FABP in the kidney. Statistical analysis of the immunoreactivity revealed that in battered and/or abused cases, Hb could be considered a specific marker. Hb and Mb were observed in the cases with general severe trauma, such as slips and falls and falls from heights. In traffic accidents, ORP150 could reflect general circulatory failure with bleeding. SP-A was observed in the cases with severe thoracic injuries, such as lung injuries and multiple thoracic fractures. L-FABP appeared in cases with renal circulatory failure as well as renal injury. These findings suggest that immunohistochemical observation of the kidneys could be a useful tool in determining several key factors, such as the severity of injury, the specific damaged organ, and the pathological condition after injury.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Biomarkers; Deoxyguanosine; Fatty Acid-Binding Proteins; Female; Forensic Pathology; Hemoglobins; Hemorrhage; HSP70 Heat-Shock Proteins; Humans; Immunohistochemistry; Injury Severity Score; Kidney; Male; Middle Aged; Multiple Trauma; Myoglobin; Proteins; Pulmonary Surfactant-Associated Protein A; Shock; Superoxide Dismutase; Young Adult

Intake of n-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been suggested to associate with an increased risk of hemorrhagic stroke. The present study was designed to investigate the hypothesis that EPA and DHA increase oxidative stress and hemorrhage volume in rats with intracerebral hemorrhagic (ICH) stroke. Thirty-five-week-old male rats were fed an American Institute of Nutrition-93M diet containing 0% (n = 27), 0.5% (n = 15), or 1% EPA + DHA of total energy for 5 weeks. Of 5 rats fed 1% EPA + DHA (41%), 5 died because of excessive bleeding within 12 hours after ICH surgery. Behavior test score and hemorrhage volume were significantly (P < .05) greater in the 1% EPA + DHA-fed rats than in other rats. Magnetic resonance imaging consistently showed that edema and bleeding were visible in only the rats fed 1% EPA + DHA. Levels of superoxide dismutase and glutathione were significantly (P < .05) lower in rats fed 0.5% and 1% EPA + DHA than those fed 0% EPA + DHA. Thiobarbituric acid-reactive substance content was significantly (P < .05) higher in 1% EPA + DHA-fed rats than in 0% and 0.5% EPA + DHA-fed rats. The level of 8-hydroxydeoxyguanosine was significantly (P < .05) higher in ICH rats with all diets than in sham surgery rats. Brain levels of EPA and DHA were highest in rats fed 1% EPA + DHA than in rats fed 0% and 0.5% EPA + DHA. These results suggested that intake of 1% EPA + DHA of total energy could lead to oxidative damage to the brain and thus increase the risk of intracerebral hemorrhagic stroke in this rat model.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Behavior, Animal; Brain; Deoxyguanosine; Dietary Fats; Docosahexaenoic Acids; Edema; Eicosapentaenoic Acid; Glutathione; Hemorrhage; Intracranial Hemorrhages; Magnetic Resonance Imaging; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley; Stroke; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances