Vet Med - Czech, 2015, 60(11):621-628 | DOI: 10.17221/8530-VETMED

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

G. Bekyarova, M. Tzaneva, M. Hristova
Medical University, Varna, Bulgaria

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.

Keywords: melatonin; Nrf2; HO-1; 4-HNE; oxidative stress; liver

Published: November 30, 2015  Show citation

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Bekyarova G, Tzaneva M, Hristova M. Melatonin protects against burn-induced hepatic oxidative injury by inducing HO-1 via the Nrf2 pathway. CAAS Agricultural Journals. 2015;60(11):621-628. doi: 10.17221/8530-VETMED.
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