Facultad de Bioquímica y Ciencias Biológicas, Departamento de Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.
Cell Biochem Funct. 2012 Dec;30(8):701-8. doi: 10.1002/cbf.2855. Epub 2012 Aug 2.
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.
肝脏再生的过程是刺激因素和肝细胞增殖抑制剂之间平衡的结果。褪黑素及其代谢产物已被发现可保护组织免受各种毒性物质和代谢过程产生的氧化损伤。此外，在大鼠肝脏中进行的研究表明，在给予抗氧化剂后，药物在肝脏线粒体中的羟化作用减少，恢复正常状态。本研究旨在确定在实验动物中，给予抗氧化剂如褪黑素是否可以防止部分肝切除（PH）后导致组织损伤和肝功能障碍的细胞事件。测定胆汁流量（BF）、肝组织氧化应激和全质膜 Na⁺/K⁺ATP 酶活性。PH 降低了 Na⁺/K⁺ATP 酶活性。PH 显著降低了 BF（36%），并促进了氧化应激，导致脂质过氧化增加，谷胱甘肽过氧化物酶和过氧化氢酶活性降低。褪黑素治疗可防止肝切除大鼠 BF 的下降，并使 Na⁺/K⁺ATP 酶活性正常化。此外，褪黑素显著减轻 PH 引起的氧化应激。这可能是褪黑素在清除各种自由基方面的更高功效的结果，也可能是因为它能够刺激抗氧化酶。我们认为，肝再生前后的氧化应激在胆汁淤积、凋亡/坏死性肝细胞损伤以及 PH 引起的肝脏转运功能障碍中起关键作用，褪黑素可以调节氧化应激程度，从而防止肝功能载体的改变。
