Tas Ufuk, Ogeturk Murat, Meydan Sedat, Kus Ilter, Kuloglu Tuncay, Ilhan Necip, Kose Evren, Sarsilmaz Mustafa
Department of Anatomy, Faculty of Medicine, Gaziosmanpaşa University, Tokat, Turkey.
Toxicol Ind Health. 2011 Jun;27(5):465-73. doi: 10.1177/0748233710389853. Epub 2011 Feb 22.
This study was designed to investigate the harmful effects of toluene inhalation in the liver of rats and possible protective effects of melatonin on these detrimental effects. For this purpose, 21 adult male Wistar-albino rats were randomly divided into three equal groups. Animals in group I were used as control. The rats in group II were exposed to toluene (3000 ppm/1 hour/day) for 4 weeks, while the rats in group III were treated with melatonin (10 mg/kg/day, intraperitoneally [ip]) plus toluene inhalation. At the end of the experimental period, liver and blood samples were taken from the decapitated animals. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin and albumin levels were determined. Liver tissue sections were stained with routine histological methods and examined under the light microscope. In addition, the sections were immunohistochemically stained using avidin-biotin-peroxidase method for determination of apoptosis. The liver tissue activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and malondialdehyde (MDA) levels were also measured. Toluene inhalation significantly increased serum ALT, AST and tissue MDA, and decreased serum albumin, but did not affect serum ALP, total bilirubin levels and tissue SOD, GSH-Px and CAT activity when compared with controls. The increases in tissue MDA and serum ALT and AST levels induced by toluene inhalation were significantly inhibited by melatonin treatment. In light microscopic observations of tissues from toluene-inhaled rats, massive hepatocyte degeneration, ballooning degeneration and mild pericentral fibrosis were observed. Bax immune reactivity was also increased significantly. Melatonin treatment decreased the balloon degeneration, fibrosis and Bax immune reactivity in the liver of toluene-inhaled rats. In view of the present findings, it is suggested that melatonin has hepatoprotective effects against toluene toxicity via primarily antioxidative properties.
本研究旨在探讨吸入甲苯对大鼠肝脏的有害影响以及褪黑素对这些有害影响可能的保护作用。为此，将21只成年雄性Wistar白化大鼠随机分为三组，每组数量相等。第一组动物作为对照。第二组大鼠暴露于甲苯（3000 ppm/1小时/天）中4周，而第三组大鼠则接受褪黑素（10 mg/kg/天，腹腔注射[ip]）并同时吸入甲苯。在实验期结束时，从断头处死的动物身上采集肝脏和血液样本。测定血清天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、碱性磷酸酶（ALP）、总胆红素和白蛋白水平。肝脏组织切片采用常规组织学方法染色，并在光学显微镜下检查。此外，采用抗生物素蛋白-生物素-过氧化物酶法对切片进行免疫组织化学染色以测定细胞凋亡。还测量了肝脏组织中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、过氧化氢酶（CAT）的活性以及丙二醛（MDA）水平。与对照组相比，吸入甲苯显著升高了血清ALT、AST和组织MDA水平，降低了血清白蛋白水平，但对血清ALP、总胆红素水平以及组织SOD、GSH-Px和CAT活性没有影响。褪黑素治疗显著抑制了吸入甲苯诱导的组织MDA以及血清ALT和AST水平的升高。在对吸入甲苯大鼠的组织进行光学显微镜观察时，发现大量肝细胞变性、气球样变性和轻度中央周围纤维化。Bax免疫反应性也显著增加。褪黑素治疗降低了吸入甲苯大鼠肝脏中的气球样变性、纤维化和Bax免疫反应性。鉴于目前的研究结果，提示褪黑素主要通过抗氧化特性对甲苯毒性具有肝脏保护作用。
