Role of melatonin in the oxidative damage prevention at different times of hepatic regeneration

• Published in: Cell biochemistry and function 2012-12, Vol.30 (8), p.701-708
• Main Authors: González, Marcela Aida, del Carmen Contini, María, Millen, Nestor, Mahieu, Stella Teresita
• Format: Article
• Language: English
• Subjects: Algorithms; Animals; Antioxidants - pharmacology; Area Under Curve; Biliary Tract - drug effects; Biliary Tract - metabolism; Biliary Tract - physiology; Catalase - metabolism; Coloring Agents - pharmacokinetics; Glutathione Peroxidase - metabolism; Hepatectomy - methods; hepatic regeneration; Humans; Lipid Peroxidation - drug effects; liver; Liver - drug effects; Liver - physiopathology; Liver - surgery; Liver Regeneration - drug effects; Male; melatonin; Melatonin - pharmacology; Metabolic Clearance Rate; oxidative stress; Oxidative Stress - drug effects; Rats; Rats, Wistar; Sodium-Potassium-Exchanging ATPase - metabolism; Sulfobromophthalein - pharmacokinetics; Time Factors
• ISSN: 0263-6484; 1099-0844
• DOI: 10.1002/cbf.2855

The process of regenerating liver is the result of a balance between stimulating factors and inhibitors of hepatocyte proliferation. Melatonin and its metabolites have been found to protect tissues against oxidative damage generated by a variety of toxic agents and metabolic processes. Furthermore, studies in liver of rats showed a decrease in the liver mitochondrial hydroxylation of drugs returning to the normal state after the administration of antioxidants. This study was designed to determine, in experimental animals, whether the administration of an antioxidant agent such as melatonin could prevent cells events leading to tissue injury and hepatic dysfunction after partial hepatectomy (PH). Biliary flow (BF), oxidative stress in hepatic tissue and Na+/K+ATPase activities in whole plasma membrane were determined. PH decreased the Na+/K+ATPase activity. PH significantly reduced the BF (36%) and promoted oxidative stress with an increase of lipoperoxidation and decrease of glutathione peroxidase and catalase activities. Treatment with melatonin prevented the decrease of BF in rats with hepatectomy and normalized the Na+/K+ATPase activity. Moreover, melatonin markedly attenuated oxidative stress produced by PH. This may be the results of the higher efficacy of melatonin in scavenging various free radicals and also because of its ability in stimulating the antioxidant enzymes. We suggest that oxidative stress before and during liver regeneration has a crucial role in cholestasis, apoptotic/necrotic hepatocellular damage and the impairment in liver transport function induced by PH and that melatonin could modulate the degree of oxidative stress and through it prevent the alterations in liver function carrier. Copyright © 2012 John Wiley & Sons, Ltd.