Abe M, Reiter R J, Orhii P B, Hara M, Poeggeler B
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78240-7762.
J Pineal Res. 1994 Sep;17(2):94-100. doi: 10.1111/j.1600-079x.1994.tb00119.x.
We evaluated the inhibitory effect of melatonin, a recently discovered scavenger of free radicals, on cataract formation in the newborn rat. The glutathione synthesis inhibitor, buthionine sulfoximine (BSO) (3 mmol/kg), was intraperitoneally injected into newborn rats for 3 consecutive days starting on day 2 after birth. These glutathione depleted rats develop cataracts. Melatonin (4 mg/kg) was injected intraperitoneally into half of the rats once a day beginning at day 2 after birth; the other half of the animals received solvent daily. The incidence of cataract was observed on day 16, after the eyes of the newborn animals had opened. Both reduced glutathione (GSH) and oxidized glutathione (GSSG) levels were measured. Cataracts were observed in all animals (18/18) treated with BSO plus solvent. The incidence of the cataract in the animals cotreated with melatonin was only 6.2% (1/15). Total lenticular glutathione (GSH + GSSG) levels in BSO only treated rats were reduced by 97%. The total glutathione in the lens of the BSO plus melatonin group was significantly higher (by 3%) than that of the BSO only group. The percentage of the total glutathione as GSSG for the BSO plus solvent group was higher than the control value. Cotreatment of BSO injected rats with melatonin (4 mg/kg/day) clearly reduced cataract formation proving that it is directly or indirectly protective against oxidative stress which accompanies glutathione deficiency. The inhibitory effects of melatonin on cataract formation in this study could be due to melatonin's free radical scavenging activity or due to its stimulatory effect on glutathione production.
我们评估了褪黑素（一种最近发现的自由基清除剂）对新生大鼠白内障形成的抑制作用。谷胱甘肽合成抑制剂丁硫氨酸亚砜胺（BSO）（3 mmol/kg）于新生大鼠出生后第2天开始连续3天腹腔注射。这些谷胱甘肽耗竭的大鼠会发展为白内障。从出生后第2天开始，每天一次对一半的大鼠腹腔注射褪黑素（4 mg/kg）；另一半动物每天接受溶剂注射。在新生动物睁眼后的第16天观察白内障的发生率。同时测量还原型谷胱甘肽（GSH）和氧化型谷胱甘肽（GSSG）的水平。接受BSO加溶剂处理的所有动物（18/18）均出现白内障。与褪黑素联合处理的动物中白内障的发生率仅为6.2%（1/15）。仅用BSO处理的大鼠晶状体总谷胱甘肽（GSH + GSSG）水平降低了97%。BSO加褪黑素组晶状体中的总谷胱甘肽明显高于仅用BSO处理的组（高3%）。BSO加溶剂组中作为GSSG的总谷胱甘肽百分比高于对照值。用褪黑素（4 mg/kg/天）对注射BSO的大鼠进行联合处理明显减少了白内障的形成，证明其对伴随谷胱甘肽缺乏的氧化应激具有直接或间接的保护作用。本研究中褪黑素对白内障形成的抑制作用可能是由于褪黑素的自由基清除活性或其对谷胱甘肽产生的刺激作用。
