8-hydroxy-2--deoxyguanosine and Burns

Severe burns with delayed resuscitation are associated with high morbidity which is attributed to ischemia-reperfusion injury. This study was undertaken to investigate the effect of hydrogen-rich saline known as a significant selective antioxidant on the inflammatory reaction induced by severe burns with delayed resuscitation. By establishing the model of severe burns with delayed resuscitation in rats, we recorded improvement on the mortality, secretion of cytokines and reaction of oxidative stress of rats treated with hydrogen-rich saline. We found that resuscitation by hydrogen-rich saline alleviated inflammation significantly. We further detected the change of the key nuclear factor NF-κB contributed to inflammation. The expression of both NF-κB and phosphorylated NF-κB in rats having severe burns with delayed resuscitation by hydrogen-rich saline was lower than that in rats with delayed resuscitation with Ringers' solution. Our data imply that hydrogen-rich saline significantly improves the inflammatory reaction in rats with severe burns with delayed resuscitation, possibly by inhibiting activation of NF-κB.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Analysis of Variance; Animals; Antioxidants; Burns; Cytokines; Deoxyguanosine; Disease Models, Animal; Fluid Therapy; Inflammation; Inflammation Mediators; Male; Monocytes; NF-kappa B; Oxidative Stress; Rats; Rats, Sprague-Dawley; Resuscitation; Shock; Sodium Chloride

To explore the effects of hydrogen-rich saline (HS) on liver of severely scalded rats with delayed resuscitation.. Twenty-four SD rats were inflicted with 40% TBSA full-thickness scald using a temperature-controlled scalding apparatus. The injured rats were divided into lactated Ringer's solution (RS) and HS groups according to the random number table, with 12 rats in each group. Rats in groups RS and HS were respectively resuscitated with an intraperitoneal injection of 4 mL × kg⁻¹ × %TBSA⁻¹ of RS or HS (self-prepared, with concentration of hydrogen 0.6 mmol/L) 6 hours after injury up to 48 hours after scald. The infusion volume of the second 24 hours after injury was a half of that of the first 24 hours. At post scald hour (PSH) 6 (before resuscitation), 12, 24, and 48, blood was collected from the heart of 3 rats in each group, and then the rats were sacrificed for harvesting liver tissue. The pathological change in liver tissue was observed with HE staining. The number of hepatic neutrophils was counted with a hematocytometer. Serum levels of AST and ALT were determined with full-automatic biochemical analyzer. Contents of TNF-α, IL-1β, IL-6, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in liver tissue were determined with ELISA. Absorbance value of malondialdehyde (MDA) in liver tissue was detected and quantified with spectrophotometer. Data were processed with analysis of variance of repeated measurement and LSD-t test.. At PSH 48, moderate infiltration of inflammatory cells and hepatic hyperemia were observed in rats of group HS as compared with group RS. At PSH 12, 24, and 48, the number of neutrophils in group HS was respectively (25.3 ± 1.8) × 10⁵, (19.6 ± 0.6) × 10⁵, and (14.1 ± 3.2) × 10⁵ cells per mililitre, and they were significantly lower than those in group RS \\[(31.9 ± 2.0) × 10⁵, (30.9 ± 2.2) × 10⁵, and (23.8 ± 3.0) × 10⁵ cells per mililitre, with t values respectively 5.6, 7.6, and 8.7, P values below 0.05\\]. At PSH 6 and 12, the serum levels of AST and ALT and the levels of TNF-α, IL-1β, and IL-6 in liver tissue were close between the two groups (with t values respectively 0.3-3.9 and 0.9-3.8, P values above 0.05). At PSH 24 and 48, the serum levels of AST and ALT in group HS were respectively (308 ± 24) and (210 ± 15) U/L and (93 ± 7) and (70 ± 5) U/L, which were significantly lower than those in group RS \\[(541 ± 39) and (505 ± 18) U/L, with t values respectively 17.5 and 16.7, P values below 0.05; (156 ± 9) and (166 ± 21) U/L, with t values respectively 30.3 and 6.9, P values below 0.05\\]. At PSH 24 and 48, the levels of TNF-α, IL-1β, and IL-6 in liver tissue in group HS were respectively (20.7 ± 1.6) and (13.7 ± 1.5) pg/mg, (7.7 ± 1.5) and (6.3 ± 1.2) pg/mg, and (8.7 ± 1.2) and (6.0 ± 2.0) pg/mg, which were significantly lower than those in group RS \\[(32.7 ± 5.0) and (25.7 ± 4.0) pg/mg, with t values respectively 5.2 and 5.7, P values below 0.05; (16.3 ± 2.5) and (12.0 ± 2.7) pg/mg, with t values both as 4.7, P values below 0.05; (14.7 ± 2.1) and (13.3 ± 1.5) pg/mg, with t values respectively 10.4 and 4.4, P values below 0.05\\]. The level of MDA at PSH 6 and levels of 8-OHdG at PSH 6 and 12 in liver tissue were close between the two groups (with t values respectively 0.1, 0.7, and 4.3, P values above 0.05). In group HS, the levels of MDA in liver tissue at PSH 12, 24, and 48 were respectively (15.3 ± 1.5), (8.7 ± 1.2), and (6.7 ± 1.5) mmol/mg, and the levels of hepatic 8-OHdG at PSH 24 and 48 were respectively (124 ± 12) and (79 ± 10) pg/mg, which were significantly lower than those in group RS \\[(27.3 ± 4.7), (20.3 ± 1.5), and (14.0 ± 1.0) mmol/mg, with t values respectively 5.2, 5.7, and 5.1, P values below 0.05; (191 ± 10) and (136 ± 15) pg/mg, with t values respectively 8.0 and 8.1, P values below 0.05\\].. Resuscitation with HS could protect liver of severely scalded rats with delayed resuscitation possibly by reducing infiltration of neutrophils, thus lowering the content of inflammatory cytokines, and effectively alleviating oxidative stress.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Burns; Deoxyguanosine; Hydrogen; Interleukin-6; Liver; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley; Rats, Wistar; Resuscitation; Sodium Chloride; Soft Tissue Injuries; Time Factors; Tumor Necrosis Factor-alpha

Oxygen-derived free radicals play important roles in pathophysiological processes in critically ill patients, but the data characterizing relationships between radicals and neuroendocrine system response are sparse. To search the cue to reduce the oxidative cellular damage from the point of view of neuroendocrine system response, we studied the indicators of neuroendocrine and inflammatory responses excreted in urine in 14 burn patients (42.3 +/- 31.4 years old, and 32.3 +/- 27.6% burn of total body surface area [%TBSA]) during the first seven days post burn. The daily mean amounts of urinary excretion of 8-hydroxy-2'-deoxy-guanosine (8-OHdG), a marker of oxidative cellular damage, were above the upper limit of the standard value during the studied period. The total amount of urinary excretion of 8-OHdG in the first day post burn correlated with burn severity indices: %TBSA (r = 0.63, p = 0.021) and burn index (r = 0.70, p = 0.008). The daily urinary excretion of 8-OHdG correlated with the daily urinary excretion of norepinephrine and nitrite plus nitrate (NOx) during the studied period except day 2 post burn, and correlated with the daily urinary excretion of 17-hydroxycorticosteriod (17-OHCS) in days 2, 3, and 7 post burn. These data suggest that oxidative cellular damage correlates with burn severity and neuroendocrine system response modulates inflammation and oxidative cellular damage. Modulation of neuroendocrine system response and inflammation in the treatment in the early phase of burn may be useful to reduce the oxidative cellular damage and to prevent multiple organ failures in patients with extensive burn.

Topics: 17-Hydroxycorticosteroids; 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Adult; Aged; Aged, 80 and over; Burns; Child; Child, Preschool; Deoxyguanosine; DNA Damage; Female; Humans; Male; Middle Aged; Neurosecretory Systems; Nitrates; Norepinephrine