Sener Göksel, Sehirli A Ozer, Ayanoglu-Dülger Gül
Marmara University, School of Pharmacy, Department of Pharmacology, Istanbul, Turkey.
Pharmacol Toxicol. 2003 Dec;93(6):290-6. doi: 10.1111/j.1600-0773.2003.pto930607.x.
Mercury exerts a variety of toxic effects in the body. Lipid peroxidation, DNA damage and depletion of reduced glutathione by Hg(II) suggest an oxidative stress-like mechanism for Hg(II) toxicity. Melatonin, the main secretory product of the pineal gland, was recently found to be a potent free radical scavenger and antioxidant. N-Acetylcysteine, a precursor of reduced glutathione and an antioxidant, is used in the therapy of acute heavy metal poisoning. In this study the protective effects of melatonin in comparison to that of N-acetylcysteine against Hg-induced oxidative damage in the kidney, liver, lung and brain tissues were investigated. Wistar albino rats of either sex (200-250 g) were divided into six groups, each consisting of 8 animals. Rats were intraperitoneally injected with 1) 0.9% NaCl, control (C) group; 2) a single dose of 5 mg/kg mercuric chloride (HgCl2), Hg group; 3) melatonin in a dose of 10 mg/kg, 1 hr after HgCl2 injection, Hg-melatonin group; 4) melatonin in a dose of 10 mg/kg one day before and 1 hr after HgCl2 injection, melatonin-Hg-melatonin group; 5) N-acetylcysteine in a dose of 150 mg/kg, 1 hr after HgCl2 injection, Hg-N-acetylcysteine group, and 6) N-acetylcysteine in a dose of 150 mg/kg one day before and 1 hr after HgCl2 injection, N-acetylcysteine-Hg-N-acetylcysteine group. Animals were killed by decapitation 24 hr after the injection of HgCl2. Tissue samples were taken for determination of malondialdehyde, an end-product of lipid peroxidation; glutathione (GSH), a key antioxidant, and myeloperoxidase activity, an index of neutrophil infiltration. The results revealed that HgCl2 induced oxidative tissue damage, as evidenced by increases in malondialdehyde levels. Myeloperoxidase activity was also increased, and GSH levels were decreased in the liver, kidney and the lungs. All of these effects were reversed by melatonin or N-acetylcysteine treatment. Since melatonin or N-acetylcysteine administration reversed these responses, it seems likely that melatonin or N-acetylcysteine can protect all these tissues against HgCl2-induced oxidative damage.
汞在体内会产生多种毒性作用。汞离子（Hg(II)）引发的脂质过氧化、DNA损伤以及还原型谷胱甘肽的消耗表明其毒性存在类似氧化应激的机制。褪黑素是松果体的主要分泌产物，最近被发现是一种有效的自由基清除剂和抗氧化剂。N-乙酰半胱氨酸是还原型谷胱甘肽的前体且是一种抗氧化剂，用于急性重金属中毒的治疗。在本研究中，对比了褪黑素与N-乙酰半胱氨酸对汞诱导的肾、肝、肺和脑组织氧化损伤的保护作用。将体重200 - 250克的Wistar白化大鼠（雌雄不限）分为六组，每组8只动物。大鼠腹腔注射：1）0.9%氯化钠，对照组（C组）；2）单剂量5毫克/千克氯化汞（HgCl2），汞组；3）在注射HgCl2后1小时注射10毫克/千克褪黑素，汞 - 褪黑素组；4）在注射HgCl2前一天及注射后1小时注射10毫克/千克褪黑素，褪黑素 - 汞 - 褪黑素组；5）在注射HgCl2后1小时注射150毫克/千克N-乙酰半胱氨酸，汞 - N-乙酰半胱氨酸组；6）在注射HgCl2前一天及注射后1小时注射150毫克/千克N-乙酰半胱氨酸，N-乙酰半胱氨酸 - 汞 - N-乙酰半胱氨酸组。在注射HgCl2后24小时断头处死动物。采集组织样本用于测定脂质过氧化终产物丙二醛、关键抗氧化剂谷胱甘肽（GSH）以及作为中性粒细胞浸润指标的髓过氧化物酶活性。结果显示，HgCl2诱导了组织氧化损伤，丙二醛水平升高即为证据。肝、肾和肺中的髓过氧化物酶活性也升高，GSH水平降低。褪黑素或N-乙酰半胱氨酸处理可逆转所有这些效应。由于给予褪黑素或N-乙酰半胱氨酸可逆转这些反应，褪黑素或N-乙酰半胱氨酸似乎能够保护所有这些组织免受HgCl2诱导的氧化损伤。
