Madhu P, Reddy K Pratap, Reddy P Sreenivasula
Department of Biotechnology, Sri Venkateswara University, Tirupati, India.
Department of Zoology, Sri Venkateswara University, Tirupati, India.
J Exp Zool A Ecol Genet Physiol. 2015 Jun;323(5):301-8. doi: 10.1002/jez.1917. Epub 2015 Mar 5.
This study was undertaken to investigate whether administration of melatonin protects PVB-Induced oxidative and metabolic toxicity in the liver of Wistar rats. Adult male Wistar rats were intraperitoneally injected with either melatonin or PVB (cisplatin, vinblastine, and bleomycin) alone or combination for a period of 9 weeks. A significant increase in lipid peroxidation levels and decrease in catalase and superoxide dismutase activity levels were observed in the liver mitochondria of rats treated with PVB indicating increased oxidative stress. PVB treatment significantly decreased the succinate dehydrogenase activity with a significant increase in lactate dehydrogenase, glucose-6-phosphate dehydrogenase, aspartate aminotransaminase, alanine aminotransaminase, and glutamate dehydrogenase activities indicating deranged hepatic metabolism. Melatonin administration, on the other hand was found to significantly improve PVB-Induced biochemical changes, bringing them closer to the controls. The results from the study provide evidence that treatment with PVB affects hepatic metabolism in rats by inducing oxidative stress followed by decreasing mitochondrial oxidation and also point towards the clinical potential of melatonin as an adjuvant therapy to conventional chemotherapeutic regimens.
本研究旨在探讨褪黑素的给药是否能保护Wistar大鼠肝脏免受顺铂、长春碱和博来霉素（PVB）诱导的氧化和代谢毒性。成年雄性Wistar大鼠单独或联合腹腔注射褪黑素或PVB，持续9周。在用PVB处理的大鼠肝脏线粒体中，观察到脂质过氧化水平显著升高，过氧化氢酶和超氧化物歧化酶活性水平降低，表明氧化应激增加。PVB处理显著降低了琥珀酸脱氢酶活性，同时乳酸脱氢酶、葡萄糖-6-磷酸脱氢酶、天冬氨酸转氨酶、丙氨酸转氨酶和谷氨酸脱氢酶活性显著增加，表明肝脏代谢紊乱。另一方面，发现给予褪黑素可显著改善PVB诱导的生化变化，使其更接近对照组。该研究结果提供了证据，表明PVB处理通过诱导氧化应激，随后降低线粒体氧化来影响大鼠肝脏代谢，同时也指出了褪黑素作为传统化疗方案辅助治疗的临床潜力。
