The role of poly(ADP-ribose) synthetase inhibition on the intestinal mucosal barrier after thermal injury

Oxidative and nitrosative stressor agents can trigger DNA strand breakage, which then activates the nuclear enzyme poly(ADP-ribose) synthetase (PARS). Activation of the enzyme depletes the intracellular concentration of energetic substrates such as nicotinamide adenine dinucleotide (NAD). This process can result in cell dysfunction and cell death. PARS inhibitors have been successfully used in ischemia–reperfusion injury, inflammation and sepsis in several experimental models. In our experimental study, we investigated the role of 3-aminobeanzamide (3-AB), a non-specific PARS inhibitor, on the intestinal mucosal barrier after burn injury. Twenty-four Wistar rats were randomly divided into three groups. The sham group (n = 8) was exposed to 21 °C water while the burn group (n = 8) and the burn + 3-AB group (n = 9) were exposed to boiling water for 12 s to produce a full thickness burn in 35–40% of total body surface area. In the burn + 3-AB group, 10 mg/kg of 3-AB was given intraperitoneally 10 min before thermal injury. Twenty-four hours later, tissue samples from mesenteric lymph nodes (MLN), spleen and liver were obtained under sterile conditions for microbiological analysis and ileum samples were obtained for biochemical and histopathological analysis. In burn group, the incidence of bacteria isolated from MLN and spleen was significantly higher than other groups (P < 0.05). 3-AB pre-treatment prevented burn induced bacterial translocation and it significantly reduced burn induced intestinal injury. Tissue malondialdehyde and 3-nitrotyrozine levels were found significantly lower than that of the burn group. These data suggest that the relationship between PARS pathway and lipid peroxidation in intestinal tissue and PARS has a role in intestinal injury caused by thermal injury.     

The influence of apoptosis of mucosal epithelial cells on intestinal barrier integrity after scald in rats

Objective: To study the influence of apoptosis of intestinal epithelial cells occurring as a result of reperfusion after burn shock on the intestinal barrier.

Methods: Fifty Wistar rats were subjected to a 30% TBSA full thickness burn, and normal saline (40 ml/kg) was given intraperitoneally immediately after the injury (group A). Ten rats served as a sham control group. The experimental group B consisted of 50 rats with identical injuries, but the normal saline was not given until 6 h after the injury. Apoptosis of intestinal epithelial cells was verified by DNA fragmentation, DNA agarose gel electrophoresis, TUNEL and electron microscope (EM), and DNA fragmentation rate was expressed as ap%. The -lactic acid in portal vein blood and intestinal diamine oxidase (DAO) were determined to evaluate the permeability and integrity of intestinal mucosal epithelium.

Results: The ap% of intestinal epithelium group B was higher than in that of group A (P<0.05 or 0.01), and its amplitude peaked at 12 h for both groups. Typical DNA ladder pattern was seen in electrophoresis in both groups. Apoptotic cells were discerned on the tips of the ileal villi at 3 h postscald by TUNEL and EM in the group B, and they appeared earlier than in the group A. There was a significant positive correlation between the ap% and the level of -lactic acid (group A: r=0.817, P<0.05; group B: r=0.727, P<0.05). On the other hand, a significant negative correlation was found between the ap% and the DAO values (group A: r=−0.937, P<0.01; group B: r=−0.836, P<0.05).

Conclusion: Apoptosis occurred in enterocytes after scald injury this pathological change might contribute to a breach of integrity of intestinal epithelium, leading to a compromise in its barrier function. Delayed fluid resuscitation might lead to an earlier and higher degree of apoptosis of the intestinal epithelial cells.     

The effects of thermal injury on transcellular permeability and intestinal P-glycoprotein in rats

This study was designed to assess intestinal drug transport via transcellular absorption and intestinal P-glycoprotein content following thermal injury in rats using propranolol as a marker substrate. Male, Sprague Dawley rats (n=30) underwent either a 30% total body surface area full thickness burn or sham treatment. Twenty-four hours later, animals were anesthetized, underwent laparotomy and the proximal jejunum was cannulated. The jejunal segment was perfused with buffer containing [³H] propranolol. Following euthanasia, jejunal tissue was harvested for Western immunoblotting of P-glycoprotein and villin, and immunohistochemical analysis of P-glycoprotein. Dramatic structural changes in jejunal integrity were observed following thermal injury; however, no significant differences in the absorption characteristics of propranolol following thermal injury were observed. Mean effective permeability of propranolol was 5.67±1.79 and 5.85±1.67 cm/s×10⁻⁵ for burn and sham groups, respectively (P>0.05). P-glycoprotein and villin content in the jejunum were significantly decreased in burn animals. The transcellular transport of propranolol is unaffected 24 h following thermal injury in rats, despite alterations in intestinal P-glycoprotein content. The decrease in P-glycoprotein and villin content in thermally injured animals may reflect loss of mature enterocytes at the villus tips.     

The effect of ethyl pyruvate on oxidative stress in intestine and bacterial translocation after thermal injury

BACKGROUND: Thermal injury causes a breakdown in the intestinal mucosal barrier due to ischemia reperfusion injury, which can induce bacterial translocation (BT), sepsis, and multiple organ failure in burn patients. The aim of this study was to investigate the effect of ethyl pyruvate (EP) on intestinal oxidant damage and BT in burn injury. MATERIALS AND METHODS: Thirty-two rats were randomly divided into four groups. The sham group was exposed to 21 degrees C water and injected intraperitoneal with saline (1 mL/100 g). The sham + EP group received EP (40 mg/kg) intraperitoneally 6 h after the sham procedure. The burn group was exposed to thermal injury and given intraperitoneal saline injection (1 mL/100 g). The burn + EP group received EP (40 mg/kg) intraperitoneally 6 h after thermal injury. Twenty-four hours later, tissue samples were obtained from mesenteric lymph nodes, spleen, and liver for microbiological analysis and ileum samples were harvested for biochemical analysis. RESULTS: Thermal injury caused severe BT in burn group. EP supplementation decreased BT in mesenteric lymph nodes and spleen in the burn + EP group compared with the burn group (P < 0.05). Also, burn caused BT in liver, but this finding was not statistically significant among all groups. Thermal injury caused a statistically significant increase in malondialdehyde and myeloperoxidase levels, and EP prevented this effects in the burn + EP group compared with the burn group (P < 0.05). CONCLUSION: Our data suggested that EP can inhibit the BT and myeloperoxidase and malondialdehyde production in intestine following thermal injury, suggesting anti-inflammatory and anti-oxidant properties of EP.     

Bisphosphonate incadronate prevents total gastrectomy-induced osteopenia in rats

Purpose. Total gastrectomy (GX) leads to osteopenia. We examined the effects of bisphosphonate incadronate (INC), a potent inhibitor of bone resorption, on bone characteristics in rats that underwent total GX. Experimental design. Male Wistar rats were divided into four groups: (1) sham-operation (n = 10); (2) total GX control (n = 6); (3) total GX with 0.3 mg kg⁻¹ day⁻¹ oral administration of INC (n = 7); and (4) total GX with 3.0 mg kg⁻¹ day⁻¹ oral administration of INC (n = 7). Results. Total GX significantly impaired bone mineral density; these effects were prevented by treatment with INC. Similarly, in GX control rats, morphometrical changes of femoral metaphysis stained with Villanueva's and Villanueva-Goldner's: bone volume, tissue volume, mineral apposition rate, labeled/bone surface, bone formation rate, osteoid volume, mineralization lag time as well as serum osteocalcin, and urinary deoxypyridinoline demonstrated simultaneous existence of both osteomalacia and osteopenia; these impairments were also prevented by INC. However, GX-induced decrease in serum levels of calcium as well as 25-hydroxyvitamin D/24,25-dihydroxyvitamin D and the increase in 1,25-dihydroxyvitamin D were not prevented by administration of INC. Conclusions. These results enhance the understanding of the unique pathophysiology of both osteomalacia and osteoporosis induced by total GX and suggest the possibility of using INC as preventive therapy for osteopenia in GX-treated patients.     

Antibiotic prophylaxis diminishes bacterial translocation but not mortality in experimental burn wound sepsis

Pseudomonas (PSA) burn wound sepsis results in prolonged bacterial translocation (BT) of enteric organisms such as E. coli to the mesenteric lymph nodes (MLN) and organs in rats. Intestinal decontamination with oral antibiotics may improve mortality after burn injury, perhaps due to decreased BT. To determine the effect of oral antibiotic prophylaxis effective against E. coli but not PSA on BT and subsequent mortality in a model of PSA burn wound sepsis, rats were given a 30% scald burn and wound inoculation with 10(8) PSA followed by randomization to either ampicillin (50 mg/kg/d) or saline gavage. Cultures of MLN, organs, blood, and cecal contents were obtained on days 1, 4, and 7 after injury, with additional animals observed for 14-day mortality. Although oral antibiotic prophylaxis resulted in increased cecal colony counts, the incidence of BT was unchanged. The number of organisms present in both the MLN and organs, however, was significantly reduced with prophylaxis, indicating cecal overgrowth by non-translocating bacteria. Reduction of the number of translocating organisms did not result in improved mean survival time after injury, suggesting that mortality from PSA burn wound sepsis occurs independently of bacterial translocation.     

Effect of early wound excision on changes in plasma nitric oxide and endothelin-1 level after burn injury: an experimental study in rats

The purpose of this study was to evaluate effects of early wound excision on changes in NO and endothelin-1 (ET-1) level in the plasma after extensive burn injury. The effects on vascular permeability and hepatic blood flow (HBF) were also assessed. Male Wistar rats were used for this study. A 30% total body surface area (TBSA) third-degree burn was made on the back. Then animals were divided into four groups. Burn group (n = 13), burn alone; infusion group (n = 13), burn injury and fluid resuscitation; early excision group (n = 13), burn injury, total wound excision at 30 min after the injury followed with immediate allogenic skin graft and fluid resuscitation; and the sham group (n = 15). The sham group and the early excision group did not show significant changes in the NO and ET-1 level in plasma during experimental period, while the burn group and the infusion group showed significant increase in the NO and ET-1. The early excision group also did not show hypovolemia, and the significant decrease in the HBF. These data suggest that the increased NO and ET-1 in plasma following thermal injury were originated from burned tissue and the removal of these injured tissue has beneficial effect on the vascular permeability and the changes in HBF.     

补充双歧杆菌可促进烫伤大鼠肠道分泌型sIgA合成与分泌

目的　探讨严重烫伤后补充双歧杆菌与肠道sIgA合成、分泌的关系。　 方法　Wistar大鼠随机分为烫伤对照组 (BC组 ,30只 )、烫伤治疗组 (BT组 ,30只 )、假伤组 (NC组 ,10只 )。BT组大鼠烫伤后灌胃双歧杆菌悬液 (5 0× 10 9CFU/ml) 1 5ml,2次 /d。观测大鼠细菌移位、肠黏膜菌群双歧杆菌量、肠道sIgA分泌和表达情况等。　 结果　 (1)伤后 3d ,BC组与BT组大鼠脏器细菌移位率分别为 4 2 %和 16 % (P =0 0 0 4 ) ;伤后 5d分别为 30 %和 8% (P =0 0 0 2 )。 (2 )伤后大鼠肠黏膜菌群中双歧杆菌减少 10～ 6 0倍 ,应用悬液后双歧杆菌明显增多。 (3)BC组大鼠肠黏液sIgA平均减少 30 % ,伤后 3d达最低 ;BT组 3d后基本恢复正常。伤后大鼠肠道sIgA表达减弱 ,补充双歧杆菌后sIgA表达显著增强。 (4)肠膜菌群中双歧杆菌量与肠黏液sIgA浓度呈显著正相关。　 结论　大鼠严重烫伤后肠道sIgA产生明显受抑制 ,补充外源性双歧杆菌可促进肠道sIgA合成与分泌。     

Specific inhibition of iNOS decreases the intestinal mucosal peroxynitrite level and improves the barrier function after thermal injury

Failure of GI tract mucosa to act as a barrier against bacterial translocation (BT) has been proposed as a potential source of sepsis and subsequent multiple organ failure post thermal injury. Nitric oxide (NO) is an inorganic radical produced by NO synthase (NOS) from -arginine. Gut mucosal constitutive NOS (cNOS) provides protection for itself. In contrast to cNOS, inducible NOS (iNOS) releases far greater amounts of NO, promotes oxidative reactions and is responsible for tissue injury. Peroxynitrite formed by the rapid reaction between superoxide and NO, is a toxic substance that contributes to tissue injury in a number of biological systems. This study was designed to investigate the effect of iNOS specific inhibitor S-methylisothiourea (SMT) on the postburn intestinal mucosal barrier function and the possible mechanism of SMT's action. Female SPF Sprague–Dawley rats underwent 35% total body surface area (TBSA) or sham burn. Either SMT or the same volume of saline was given (5 mg/kg, i.p. q 12 h) for 2 days to assess the effect of iNOS inhibition. On postburn day 2, the intestinal mucosal cNOS and iNOS activity were assayed by using Griess' reagent, the mesenteric lymph node (MLN), spleen and liver were collected and cultured for BT assay and the cellular localization of nitrotyrosine, a marker for peroxynitrite activity, was examined by immunostaining. After thermal injury in rats, administration of SMT for 2 days decreased the intestinal mucosal iNOS activity/tNOS activity ratio and the BT incidence. Nitrotyrosine immunostaining of the intestinal mucosa showed a decrease in the SMT-treated group. These findings suggest that SMT, a specific inhibitor for iNOS improves the barrier function after burn by suppression of the intestinal mucosal iNOS activity. The decrease in NO production resulted in decreased formation of peroxynitrite and subsequently decreased damage of mucosal tissue.     

Melatonin improves oxidative organ damage in a rat model of thermal injury

Animal models of burn injury indicate oxygen radicals as causative agents in the local wound response, as well as in the development of burn shock and distant organ injury. This study was designed to determine the possible protective effect of melatonin treatment against oxidative damage in the liver, lung and intestine induced by burn injury. Under ether anaesthesia, the shaved dorsum of rats was exposed to a 90 degrees C bath for 10s to induce burn injury. Rats were decapitated either 3 or 24h after burn injury. Melatonin was administered i.p. immediately after burn injury. In the 24h burn group, melatonin injections were repeated for two more occasions. In the sham group the same protocol was applied except that the dorsum was dipped in a 25 degrees C water bath for 10s. Liver, lung and intestine tissues were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and protein oxidation (PO). Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, significant increases in MDA and PO levels, and MPO activity at postburn 3 and 24h. Treatment of rats with melatonin (10mg/kg) significantly elevated the reduced GSH levels while it decreased MDA and PO levels as well as MPO activity.     

Effects of N-acetylcysteine on lung glutathione levels in rats after burn injury

This study was designed to determine the effect of N-acetylcysteine (NAC, a natural hydroxyl radical scavenger) treatment on levels of pulmonary malondialdehyde (MDA, the end product of lipid peroxidation) and glutathione (GSH, a natural antioxidant) in thermally injured rats. Severe skin scald injury (30 percent TBSA) caused a significant decrease in GSH levels, and a significant increase in MDA levels in lung tissue both at 1 h and 1 day postburn injury.

Treatment of rats with NAC (15 mg/kg intraperitoneally, 15 min and 12 h following the burn) significantly improved GSH levels, and decreased ongoing lipid peroxidation at 1 day.

This study showed that thermal injury resulted in increased pulmonary lipid peroxidation, and this remote organ injury was decreased by treatment with NAC. In addition NAC, a scavenger of hydroxyl radicals, improved GSH levels in the lungs. The higher level of GSH in the lungs of the burned rats treated with NAC could be due to either a decrease in the rate of degradation of GSH or to an increase in its synthesis. No data about these possibilities are provided.     

Effect of Ligustrazine on liver injury after burn trauma

This study was designed to investigate the effect of Ligustrazine on burn-induced liver injury as well as the activation of nuclear factor kappaB (NF-kappaB) in severely burned rats. Sprague-Dawley rats were divided into three groups: (1) sham group, rats who underwent sham burn; (2) control group, rats given third-degree burns over 30% total body surface area (TBSA) and lactated Ringer solution for resuscitation; (3) Ligustrazine group, rats given burn and lactated Ringer's solution with Ligustrazine inside for resuscitation. Liver injury was assessed at 24 h post-burn by serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as liver wet/dry weight ratio. Liver myeloperoxidase (MPO) activity was also analyzed. Hepatic NF-kappaB activity was examined by electrophoretic mobility shift assay (EMSA). Burn results in hepatic dysfunction and increased hepatic NF-kappaB activity, elevated liver wet/dry ratio and hepatic MPO activity. Ligustrazine inhibited these changes and alleviated burn-mediated hepatic dysfunction. The data indicated that Ligustrazine has a protective effect on burn-induced liver injury and possible mechanism may be attributed to its inhibitory action on the activation of NF-kappaB following burn trauma.     

The effects of ketamine and propofol on bacterial translocation in rats after burn injury

BACKGROUND: Bacterial translocation (BT) occurs after thermal injury and may result from an ischemic intestinal insult. The aim of the study was to investigate the effects of ketamine and propofol as anesthetic agents on BT in an animal model of burn injury. METHODS: Sixty male Wistar Albino rats were randomly assigned to six groups of 10 rats each. Anesthesia was induced and maintained with ketamine in groups 1, 2 and 3 and with propofol in groups 4, 5 and 6 during 6 h. Groups 2, 3, 5 and 6 received 30% total body surface area (TBSA) third-degree burns. Groups 1 and 4 had no burn injury. Then, they were allowed to recover from the anesthesia at the end of 6 h. Mean arterial pressure (MAP) was monitored continuously and maintained within 10% of baseline (before burn injury) levels in all animals. Animals in groups 3 and 6 had a laparotomy to obtain a tissue sample from the terminal ileum for determination of intestinal lipid peroxidation by-product malondialdehyde (MDA) before (baseline) and 6 and 24 h after burn injury (ABI). So these animals were not included in the BT studies. At postburn 24 h, animals in groups 1, 2 and 4, 5 were sacrified and samples were taken from the mesenteric lymph nodes (MLN), liver and spleen for bacteriologic cultures. RESULTS: The incidence of BT was found to be significantly higher in group 2 than in all the other groups. Bacterial translocation incidence of group 5 was not significantly different from that of groups 4 and 1. Group 5 was associated with a significantly reduced number of enteric organisms per gram of tissue compared to group 2. Baseline MDA contents of groups 3 and 6 were similar. Ileal MDA levels were increased in group 3, but there were no significant changes in group 6 at 6 and 24 h ABI compared to baseline. CONCLUSION: Our results suggest that propofol as an anesthetic agent may prevent BT by scavenging reactive oxygen species and inhibiting lipid peroxidation in an animal model of burn injury.     

Bacterial translocation and intestinal atrophy after thermal injury and burn wound sepsis.

Bacterial translocation (BT) occurs after thermal injury in rodents in association with intestinal barrier loss. Infection complicating thermal injury may also affect the intestine producing bowel atrophy. To study these relationships, Wistar rats received either 30% scald followed by wound inoculation with Pseudomonas; 30% scald with pair feeding to infected animals; or sham injury as controls. On days 1, 4, and 7 after injury animals were killed with examination of the bowel and culture of the mesenteric lymph nodes (MLN), livers, spleens, and blood. All burned animals demonstrated BT to the MLN on day 1 after injury, but only burn-infected animals had continued BT on days 4 and 7, with progression of BT to the abdominal organs and blood. Burn injury and infection also resulted in significant atrophy of small bowel mucosa temporally associated with continued BT. Thus injury complicated by infection results in prolonged and enhanced bacterial translocation, perhaps due to failure to maintain the mucosal barrier.     

The healing-promoting effect of saliva on skin burn is mediated by epidermal growth factor (EGF): role of the neutrophils

Local skin trauma induces inflammatory responses resulting in local tissue and distant organ injury. EGF, a polypeptide hormone, mainly produced in saliva, is one of the major accelerators in wound healing. Wistar albino rats of both sexes received either bovine serum albumin or EGF (10 microg/kg) subcutaneously before a circular (18 mm diameter) partial thickness burn was induced. Afterwards, some rats were placed in separate cages to prevent licking, while the others were caged together to allow wound-licking. Treatments were continued for 5 more days and on the 5th day animals were decapitated. Histopathological analysis of skin damage and dermal myeloperoxidase (MPO) activity, as an index for neutrophil activity, were evaluated. Oxidant injury to the liver and intestines was determined by measuring glutathione (GSH) and malondialdehyde (MDA) levels, as well as MPO activity. The results demonstrate that healing of the burn wound on the skin is accelerated by both wound-licking and EGF administration, which also attenuated tissue neutrophil accumulation, suggesting the role of neutrophils as the source of mediators involved in delayed epithelial regeneration. Moreover, local dermal burn results in oxidant injury to the liver, concomitant with significant elevations in hepatic and intestinal GSH levels. Exogenous administration of EGF at physiological doses had no effect on inflammatory responses of the distant organs, while allowing the rats to lick the wound reduced the oxidant injury to the liver. Since saliva or EGF enhances skin wound healing, topical use of EGF-rich artificial saliva merits consideration for its use in burn patients.     

Intravenous lidocaine infusion in the treatment of experimental human skin burns - digital colour image analysis of erythema development

Previous studies have shown that local anaesthetics possess a wide range of effects on the pathophysiology of burns, including inhibition of burn oedema and inhibition of progressive burn ischemia. The present randomised double-blind cross-over study in six volunteers investigated the effects of intravenous lidocaine infusion on partial thickness skin burns. A thermoprobe was used to induce a standardised thermal injury (1 cm²) on the flexor side of one forearm and was repeated on the opposite side 1 week later. Subjects received either an intravenous bolus dose of lidocaine (1 mg kg⁻¹) immediately after the thermal trauma followed by continuous intravenous infusion of lidocaine (40 μg kg⁻¹ min⁻¹) during 4 h or equal volumes of isotonic saline. Macrophotographs of the experimental skin area were taken preburn and 1, 2, 3, 4, and 12 h postburn and evaluated by computerised image colour analysis using normalised rgb (n-rgb) and Hue–Saturation–Intensity (HSI) colour systems as a quantitative measure of pathophysiological events. Maximum erythema occurred 2–3 h postburn. Differences between lidocaine- and placebo-treated burns were not significant during the first 4 h postburn. At 12 h postburn, the lidocaine-treated burn demonstrated a significantly faster restitution of residual erythema compared to control sites. The present study shows that intravenous lidocaine significantly inhibits the long-term inflammation-induced tissue responses to thermal trauma.     

Psychological consequences of burn injury

The major psychological sequelae experienced by patients 1 year after burn injury were investigated. Data were collected on a consecutive series of adult burn patients, (n = 55), including major demographic and epidemiological characteristics. Participants (n = 23) completed the Hospital Anxiety Depression Scale (HADS), the Impact of Event Scale (IES) and a questionnaire covering functional impairment, visibility of the burn, experience of pain, etc. Over one-third of the patients (36.4 per cent) were found to have premorbid characteristics which could predispose them to injury. Over one-third (34.7 per cent) were still experiencing significant psychological problems. Anxiety was most common, followed by posttraumatic stress symptoms and depression. The visibility of the burn was found to be a useful factor in the prediction of psychological outcome (P = 0.001−0.018). No additional variables were found to increase the significance of prediction. Patients indicated that practical advice in the form of staff-led discussions, before or immediately after discharge, would be the most valuable help.     

Role of nitric oxide in myocardial dysfunction after combined burn and smoke inhalation injury

This study tested the hypothesis that nitric oxide (NO) synthesized from inducible NO synthase (iNOS) is responsible for the cardiac dysfunction observed after burn and smoke inhalation injury. Twelve sheep received 40% third-degree burn and smoke inhalation under halothane anesthesia. The animals were divided into two groups: a MEG group [iNOS was inhibited with mercaptoethylguanidine (MEG), a selective inhibitor of iNOS, n=6] and a control group (n=6). The control group showed a significant increase in NO₂⁻/NO₃⁻ (NO_x) concentration, metabolite of NO, in plasma after 24 h, whereas the MEG group did not. In the control group, cardiac depression was observed immediately after injury associated with hemoconcentration. Cardiac function returned to a normal level within 6 h following injury. In the control group cardiac dysfunction was observed again after 24 h although the hemoconcentration peaked at 24 h after injury and then began to resolve. In the MEG group, cardiac depression and hemoconcentration were not observed. The present data suggest that cardiac depression seen with this combination injury consists of two phases and that the later phase is mediated by iNOS–NO.     

The role of hypothermia in gluconeogenesis and sensitivity to insulin after burns

The contribution of post-burn hypothermia to alterations in carbohydrate metabolism was investigated at 4, 8 and 24 h following a 27 per cent body surface scald produced in rats previously fasted for 24 h. Fasted control animals were evaluated at the same time intervals as the burned animals. Following burn injury, body temperature fell to 31·3 ± 0·3 °C (± s.e.) at 4 h and returned to control values by 24 h post burn. At each time interval, serum glucose was 2-fold higher, serum corticosterone was more than 4-fold higher and plasma glucagon was more than 2-fold higher than corresponding controls. Serum insulin did not differ from controls at 4 h, but then rose linearly to a value almost 5-fold higher than the control value at 24 h post burn. The addition of 20 mmol alanine to liver slices from rats 4 h post burn and controls incubated at 37 °C increased glucose production in vitro, the effect being greater in burned rats. In contrast, liver slices from burned and control rats did not convert alanine to glucose (or tissue glycogen) when incubated at the body temperature of rats 4 h post burn — 31 °C. The addition of insulin in vitro produced a similar increase in glucose uptake by soleus muscle from both rats 4-h post burn and controls when incubated at 37 °C, but the effect was significantly reduced in both groups of muscles when incubated at 31 °C. The data suggest that post-burn hypothermia modifies the metabolic response to injury by opposing the stimulation of gluconeogenesis and that it is the direct cause of decreased sensitivity to insulin observed acutely after the experimental burn.     

Leukotriene receptor blocker montelukast protects against burn-induced oxidative injury of the skin and remote organs

Thermal injury elicits several systemic consequences, among them the systemic inflammatory response where the generation of reactive oxygen radicals and lipid peroxidation play important roles. In the present study, we investigated whether the leukotriene receptor blocker montelukast is protective against burn-induced remote organ injury. Under brief ether anaesthesia, shaved dorsum of the rats was exposed to 90 degrees C (burn group) or 25 degrees C (control group) water bath for 10 s. Montelukast (10 mg/kg) or saline was administered intraperitoneally immediately after and at the 12th hour of the burn injury. Rats were decapitated 24 h after burn injury and the tissue samples from lung, liver, kidney and skin were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Tissues were also examined microscopically. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and creatinine, urea (BUN) concentrations were determined to assess liver and kidney function, respectively. Tumor necrosis factor-alpha (TNF-alpha) and lactate dehydrogenase (LDH) were also assayed in serum samples. Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, which was accompanied with significant increases in MDA level, MPO activity and collagen content of tissues. Similarly, serum ALT, AST and BUN levels, as well as LDH and TNF-alpha, were elevated in the burn group as compared to control group. On the other hand, montelukast treatment reversed all these biochemical indices, as well as histopathological alterations, which were induced by thermal trauma. Findings of the present study suggest that montelukast possesses an anti-inflammatory effect on burn-induced damage in remote organs and protects against oxidative organ damage by a neutrophil-dependent mechanism.