Melatonin exhibits a wide variety of biological activity including antioxidant and anti-inflammatory effects. We have previously reported its protective effect on hepatic oxidative hepatic injury in burns. In this study, we investigated the role of nuclear factor kappa B (NF-kB) in melatonin-mediated protection against liver injury by using the burned-rat model. Melatonin (N-acetyl-5-methoxytriptamin, 10mgl kg (-1), Lp.) was administered immediately and 12 hours after thermal skin injury. Hepatic NF-kB expression was determined by Western blotting. TNF-a level in liver homogenate was quantified using enzyme-linked immunosorbent assay (ELISA) kit. Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were determined to assess liver injury at the 24 th hour after burns. Thermal skin injury caused significant elevation of hepatic NF-kB expression by 48%, TNF-a level by 55% and plasma AST and ALT activities by 2-and 3-fold, respectively, in comparison with normal control rats. Treatment with melatonin decreased significantly elevated hepatic NF-kB activity and TNF-a, maintaining the levels close to the control values Melatonin suppressed the elevation of plasma AST and ALT activities (p

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The aim of this study was to investigate the effects of melatonin on burn-induced inflammatory responses and coagulation disorders in a rat model. Under ether anesthesia, shaved dorsa of rats were exposed to 90 degrees C for 10 s to induce burn injury. Melatonin (10 mg/kg) was administered immediately and after 12 h. Standard coagulation tests (prothrombin activity [PA] and activated partial thromboplastin time [aPTT]), platelet number and morphology; proinflammatory markers (C-reactive protein [CRP] and fibrinogen) and lipid peroxidation marker (malondialdehyde [MDA]) levels were assayed. Thermal injury increased the levels of MDA (by 76%, P < 0.0001), CRP (by 33%, P < 0.0001), fibrinogen (4.5-fold, P < 0.0001) and PA (by 37%; P < 0.01). Changes in aPTT and platelet numbers were nonsignificant. Melatonin diminished the elevated CRP and fibrinogen levels, normalized MDA levels, platelet morphology and decreased PA. A positive association of MDA with fibrinogen and MDA with PA were noted after melatonin treatment. To conclude, melatonin as an antioxidant and anti-inflammatory agent exerted a suppressive effect on burn-induced disorders in blood coagulation and might be useful in the prevention of disseminated intravascular microthrombosis.

Melatonin, a major hormone of pineal gland, was recently show to attenuate acute gastric lesions induced by strong irritants because of the scavenging of free radicals. The effect of melatonin on burninduced gastric mucosal injury due to the skin burn is unclear. PURPOSE: This study investigated heme oxygenase-1 and markers linked with oxidative stress in gastric mucosa and the effect of melatonin in burn rat model. METHODS: Melatonin was applied immediately and 12 hours after 30% of total body surface area burns. Using light immunohistochemistry the expression of gastric mucosal inducible nitric oxide synthase (iNOS) and heme oxygenase (HO-1) was found out. Malondialdehyde (MDA) as a marker of oxidative injury was determined in gastric mucosa by the thiobarbituric acid method. RESULTS: Gastric MDA and iNOS levels were increased significantly after severe burn (p<0.05, p<0.0001, respectively). The increased HO-1 expression in the burned group was found out (p<0.05). Melatonin restricted the increased MDA (p<0.05) and iNOS (p<0.05) levels, and augmented the increase in HO-1 expression in gastric mucosa (p<0.05). In conclusion, melatonin ameliorates gastric mucosal injury via induction of antioxidant enzyme HO-1 and inhibition of oxidative stress beyond local burn skin injury.

Melatonin exerts beneficial effects on early liver injury by modulating hepatic oxidative stress. In order to understand the protective effect of melatonin against burn-induced hepatic injury we investigated the expression of 4-hydroxynonenal (4-HNE), a main product of lipid peroxidation and mediator of oxidative injury, the inducible heme-oxygenase-1 (HO-1), an antioxidant enzyme, and the anti-oxidative stress regulator erythroid 2-related factor 2 (Nrf2) in a burn rat model. Expression and localisation of HO-1, 4-HNE and Nrf2 in liver were investigated using light immunochemistry. Thermal skin injury caused a significant elevation in hepatic 4-HNE and degenerative liver changes. Concurrently, there was increased expression of HO-1, a rate-limiting enzyme for haem degradation and an oxidative stress marker in sinusoidal endothelial cells (SECs) and hepatocytes without changes in Nrf2 expression in the liver. Melatonin (20 mg/kg b.w.) augmented the increase in HO-1 expression, upregulated Nrf2 expression and also led to decreased 4-HNE levels and reduced levels of histopathological changes in rat liver. In conclusion, our results suggest that melatonin ameliorates burn-induced liver injury through the inhibition of oxidative stress, upregulation of the antioxidant enzyme HO-1 and activation of the antioxidant Nrf2 pathway. Stimulation of cellular protective mechanisms by activating the antioxidant stress response through Nrf2 is a new mechanism for protection against liver damage in burns.