Kim S J, Reiter R J, Rouvier Garay M V, Qi W, El-Sokkary G H, Tan D X
Department of Cellular and Structural Biology, The University of Texas Health Science Center, San Antonio 78284-7762, USA.
Toxicology. 1998 Sep 15;130(2-3):183-90. doi: 10.1016/s0300-483x(98)00111-5.
The degree of lipid peroxidation (LPO) as indicated by the levels of thiobarbituric acid reactive substances, malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA), and the activity of sorbitol dehydrogenase (SDH) in serum as parameters of hepatotoxicity were studied in rats treated with a single intraperitoneal (i.p.) injection of the hepatocarcinogen 2-nitropropane (2-NP). Since melatonin, the main secretory product of the pineal gland, has been shown to protect against a number of toxic agents, it was given 30 min before 2-NP to test its protective effect against 2-NP toxicity. Significant increases in LPO in liver (P<0.0001), lung (P<0.05) and kidney (P<0.0001) were observed 24 h after 4 mmol/kg 2-NP while serum SDH activity was increased 470-fold. All parameters showed time (0, 4, 8, 24 h) and dose (0, 1, 2, 3, 4 mmol/kg) dependency. The induction of LPO by 2-NP was significantly reduced in lung and kidney when melatonin (2.5, 5 or 10 mg/kg) was given prior to 2-NP administration. The elevation in serum SDH caused by 2-NP was also reduced when melatonin was given. These findings show that 2-NP induces LPO and that pharmacological levels of melatonin can reduce the toxicity of this hepatocarcinogen.
以硫代巴比妥酸反应性物质、丙二醛（MDA）和4-羟基烯醛（4-HDA）水平表示的脂质过氧化（LPO）程度，以及血清中山梨醇脱氢酶（SDH）的活性作为肝毒性参数，在单次腹腔注射肝癌致癌物2-硝基丙烷（2-NP）的大鼠中进行了研究。由于松果体的主要分泌产物褪黑素已被证明可抵御多种有毒物质，在注射2-NP前30分钟给予褪黑素，以测试其对2-NP毒性的保护作用。在给予4 mmol/kg 2-NP后24小时，观察到肝脏（P<0.0001）、肺（P<0.05）和肾脏（P<0.0001）中的LPO显著增加，而血清SDH活性增加了470倍。所有参数均显示出时间（0、4、8、24小时）和剂量（0、1、2、3、4 mmol/kg）依赖性。在给予2-NP之前给予褪黑素（2.5、5或10 mg/kg）时，2-NP诱导的肺和肾脏LPO显著降低。给予褪黑素时，2-NP引起的血清SDH升高也有所降低。这些发现表明，2-NP诱导LPO，而药理学水平的褪黑素可降低这种肝癌致癌物的毒性。
