Cam Meryem, Yavuz Ozlem, Guven Aysel, Ercan Feriha, Bukan Neslihan, Ustündag Nil
Department of Histology and Embryology, Abant Izzet Baysal University, School of Medicine, Duzce, Turkey.
J Pineal Res. 2003 Oct;35(3):212-20. doi: 10.1034/j.1600-079x.2003.00082.x.
The aim of this study was to investigate the effects of melatonin as an antioxidant, on prevention and treatment of streptozotocin (STZ)-induced diabetic renal injury in rats. Male Wistar rats were divided into four groups: (1) untreated, (2) melatonin-treated, (3) untreated diabetic (UD), (4) melatonin-treated diabetic (MD). Experimental diabetes was induced by single dose (60 mg/kg, i.p.) STZ injection. For 3 days prior to administration of STZ, melatonin was injected (200 microg/kg/day, i.p.); these injections were continued until the end of the study (4 weeks). Malondialdehyde (MDA) levels as a marker of lipid peroxidation were significantly increased in the renal homogenates of UD animals and decreased after melatonin administration. The activity of the antioxidative enzyme glutathione peroxidase (GSH-Px) was significantly reduced in UD rats. Melatonin treatment reversed STZ-induced reduction of GSH-Px activity without having an effect on blood glucose. Upon histopathological examination, it was observed that the melatonin treatment prevented the renal morphological damage caused by diabetes. Upon immunohistochemical investigation, glomerular anti-laminin beta1 staining decreased in MD rats. Additionally, no tubular anti-IGF-1 staining was observed in melatonin-treated rats. In conclusion, chronically administered melatonin reduced renal injury in STZ-induced diabetic rats and thus it may provide a useful therapeutic option in humans to reduce oxidative stress and the associated renal injury in patients with diabetes mellitus.
本研究旨在探讨褪黑素作为一种抗氧化剂对链脲佐菌素（STZ）诱导的大鼠糖尿病肾损伤的预防和治疗作用。雄性Wistar大鼠分为四组：（1）未治疗组，（2）褪黑素治疗组，（3）未治疗糖尿病组（UD），（4）褪黑素治疗糖尿病组（MD）。通过单次腹腔注射STZ（60 mg/kg）诱导实验性糖尿病。在给予STZ前3天，腹腔注射褪黑素（200 μg/kg/天）；这些注射持续至研究结束（4周）。作为脂质过氧化标志物的丙二醛（MDA）水平在UD动物的肾匀浆中显著升高，而在给予褪黑素后降低。抗氧化酶谷胱甘肽过氧化物酶（GSH-Px）的活性在UD大鼠中显著降低。褪黑素治疗逆转了STZ诱导的GSH-Px活性降低，且对血糖无影响。经组织病理学检查，发现褪黑素治疗可预防糖尿病引起的肾脏形态损伤。经免疫组织化学研究，MD大鼠肾小球抗层粘连蛋白β1染色降低。此外，在褪黑素治疗的大鼠中未观察到肾小管抗IGF-1染色。总之，长期给予褪黑素可减轻STZ诱导的糖尿病大鼠的肾损伤，因此它可能为人类提供一种有用的治疗选择，以减轻糖尿病患者的氧化应激及相关肾损伤。
