Li Z R, Reiter R J, Fujimori O, Oh C S, Duan Y P
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284-7762, USA.
J Pineal Res. 1997 Apr;22(3):117-23. doi: 10.1111/j.1600-079x.1997.tb00312.x.
The purpose of this study was to examine the influence of exogenously administered melatonin on cataract formation and lipid peroxidation in newborn rats treated with buthionine sulfoximine (BSO), a drug which inhibits the rate-limiting enzyme in glutathione (GSH) synthesis, gamma-glutamylcysteine synthase, thereby depleting animals of their stores of the important intracellular antioxidant, GSH. BSO (3 mmol/kg BW) was given for three consecutive days beginning on postnatal day 2; melatonin (4 mg/kg) was injected daily beginning on postnatal day 2 and continuing until the animals were killed (either day 9 or day 17 after birth). None of the control animals (rats treated with neither BSO nor with melatonin) developed lenticular opacification during the observation period. In the BSO-treated rats, 16 of 18 animals (89%) had observable cataracts when they were examined. In rats that received both BSO and melatonin, the incidence of cataracts was highly significantly decreased, i.e., only 3 of 18 rats (7%) had observable cataracts. In addition to cataracts, the level of lipid peroxidation products (malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA)) was examined in the lens, brain, liver, lung, and kidney of control and experimental animals. In BSO-treated rats, the lens, kidney, and lung exhibited increased levels of MDA plus 4-HDA relative to those measured in the control rats; these increases were reversed in the BSO-treated rats who were injected with melatonin daily. While BSO administration did not increase basal levels of MDA plus 4-HDA in either the brain or liver, melatonin reduced levels of lipid peroxidation products below those measured in the control rats (at 17 days after birth). The changes induced by melatonin are consistent with the free-radical scavenging and antioxidative properties of this indole.
本研究的目的是探讨外源性给予褪黑素对用丁硫氨酸亚砜胺（BSO）处理的新生大鼠白内障形成和脂质过氧化的影响。BSO是一种抑制谷胱甘肽（GSH）合成限速酶γ-谷氨酰半胱氨酸合成酶的药物，从而耗尽动物体内重要的细胞内抗氧化剂GSH的储备。从出生后第2天开始连续3天给予BSO（3 mmol/kg体重）；从出生后第2天开始每天注射褪黑素（4 mg/kg），持续至动物处死（出生后第9天或第17天）。在观察期内，没有一只对照动物（既未用BSO也未用褪黑素处理的大鼠）出现晶状体混浊。在接受BSO处理的大鼠中，检查时18只动物中有16只（89%）出现了可观察到的白内障。在同时接受BSO和褪黑素的大鼠中，白内障的发生率显著降低，即18只大鼠中只有3只（7%）出现了可观察到的白内障。除了白内障外，还在对照和实验动物的晶状体、脑、肝、肺和肾中检测了脂质过氧化产物（丙二醛（MDA）和4-羟基烯醛（4-HDA））的水平。在接受BSO处理的大鼠中，相对于对照大鼠测量的水平，晶状体、肾和肺中MDA加4-HDA的水平升高；在每天注射褪黑素的接受BSO处理的大鼠中，这些升高得到了逆转。虽然给予BSO并未增加脑或肝中MDA加4-HDA的基础水平，但褪黑素使脂质过氧化产物水平低于对照大鼠（出生后第17天）测量的水平。褪黑素诱导的这些变化与该吲哚的自由基清除和抗氧化特性一致。
