Zasada Krzysztof, Karbownik-Lewinska Malgorzata
Department of Oncological Endocrinology, Medical University of Lodz, Lodz, Poland Polish Mother's Memorial Hospital, Research Institute, Lodz, Poland.
Department of Oncological Endocrinology, Medical University of Lodz, Lodz, Poland Polish Mother's Memorial Hospital, Research Institute, Lodz, Poland
Toxicol Ind Health. 2015 Dec;31(12):1195-201. doi: 10.1177/0748233713491799. Epub 2013 May 30.
Nitrobenzene is a carcinogen, which induces-among others-thyroid tumors. Melatonin is an effective antioxidant, whereas some antioxidative effects of propylthiouracil (PTU; an antithyroid medication used for the treatment of thyrotoxicosis) were also found. The aim of the study was to compare protective effects of melatonin and PTU against lipid peroxidation in homogenates of porcine thyroids, incubated in the presence of nitrobenzene.
Homogenates of porcine thyroids were incubated for 30 min in the presence of nitrobenzene (0.001, 0.01, 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, 7.5, and 10.0 mM). The level of lipid peroxidation products (malondialdehyde + 4-hydroxyalkenals) was measured spectrophotometrically. Nitrobenzene (7.5 and 10.0 mM) increased lipid peroxidation in the homogenates of porcine thyroids. Subsequently, homogenates of porcine thyroids were incubated for 30 min in the presence of nitrobenzene (7.5 mM) plus one of the antioxidants: melatonin (0.000001, 0.00001, 0.0001, 0.001, 0.01, 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, and 7.5 mM) or PTU (0.01, 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, and 7.5 mM).
Lipid peroxidation caused by nitrobenzene was effectively prevented by melatonin, with the lowest effective concentration of 0.0001 mM, being only two orders of magnitude higher than physiological blood concentration in humans. At the same time, PTU revealed protective effects only in the highest used concentration (7.5 mM), which is practically never reached during pharmacological treatment in patients with thyrotoxicosis.
Melatonin can serve as an effective agent in protection against nitrobenzene-induced lipid peroxidation in porcine thyroid.
硝基苯是一种致癌物,可诱发甲状腺肿瘤等疾病。褪黑素是一种有效的抗氧化剂,同时也发现丙硫氧嘧啶(PTU,一种用于治疗甲状腺毒症的抗甲状腺药物)具有一些抗氧化作用。本研究的目的是比较褪黑素和PTU对在硝基苯存在下孵育的猪甲状腺匀浆中脂质过氧化的保护作用。
将猪甲状腺匀浆在硝基苯(0.001、0.01、0.1、0.25、0.5、1.0、2.5、5.0、7.5和10.0 mM)存在下孵育30分钟。通过分光光度法测量脂质过氧化产物(丙二醛+4-羟基烯醛)的水平。硝基苯(7.5和10.0 mM)增加了猪甲状腺匀浆中的脂质过氧化。随后,将猪甲状腺匀浆在硝基苯(7.5 mM)加一种抗氧化剂的存在下孵育30分钟:褪黑素(0.000001、0.00001、0.0001、0.001、0.01、0.1、0.25、0.5、1.0、2.5、5.0和7.5 mM)或PTU(0.01、0.1、0.25、0.5、1.0、2.5、5.0和7.5 mM)。
褪黑素有效预防了硝基苯引起的脂质过氧化,最低有效浓度为0.0001 mM,仅比人类生理血药浓度高两个数量级。同时,PTU仅在最高使用浓度(7.5 mM)时显示出保护作用,而在甲状腺毒症患者的药物治疗过程中几乎从未达到该浓度。
褪黑素可作为预防硝基苯诱导的猪甲状腺脂质过氧化的有效药物。