Melatonin Protection against Burn-Induced Hepatic Injury by Down-Regulation and Nuclear Factor Kappa B Activation

Abstract

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<O.OOI), which remained significantly increased compared to controls. In conclusion, thermal skin injury causes hepatic NF-kB activation that may mediate the release of hepatic TNF-a and contribute to liver damage. Melatonin protects against burn-induced hepatic injury as to a certain extent this effect may result from the suppression ofNF-kB-mediated inflammatory response.

Melatonin and ubiquitin: what’s the connection?

“…Melatonin reduces nf-κB binding in spleen [89]. a number of laboratories report melatonin-induced inhibition of nK-κB activity or inhibition of nf-κB activation [90][91][92][93][94][95][96][97][98][99][100]. these results suggest an interaction of melatonin and the ubiquitin-proteasome system in the activation of nf-κB.…”

Melatonin protects against burn-induced hepatic oxidative injury by inducing HO-1 via the Nrf2 pathway

“…Thermal skin injury is a strong inducer of oxidative stress, and lipid peroxidation is the most prominent among the many biological targets of oxidative stress (Bekyarova et al 2009;Bekyarova et al 2012). 4-HNE is one of the most toxic molecules of lipid peroxidation and a biomarker of oxidative injury.…”

“…The mechanism of burn-induced injury is not completely understood; however, several mechanisms, including hypoxia, free radicals, inflammation, and apoptosis are thought to be involved (Jeschke et al 2001). The excessive production of free radicals such as superoxide anion, hydrogen peroxide and hydroxyl radicals as well as the occurrence of lipid peroxidation products such as malondialdehyde (MDA) due to oxidative stress are associated with burn-induced liver dysfunction (Horton 2003;Bekyarova et al 2009;Bekyarova et al 2012). Burn reduces the antioxidant status thus leading to a failure of the antioxidant defence against free-radical damage (Piantadosi et al 2006;Parihar et al 2008;Vinha et al 2013).…”

Impact of melatonin on immunity: a review

“…According to that evidence, application of melatonin would be suitable for relief from those diseases and can be designated as a drug for supportive care [72]. The supportive role of melatonin in burn therapy [73,74] and inflammatory bowel disease [75] are two examples.…”