Cataractogenesis and lipid peroxidation in newborn rats treated with buthionine sulfoximine: preventive actions of melatonin.
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.
Li
Z R
ZR
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284-7762, USA.
Reiter
R J
RJ
Fujimori
O
O
Oh
C S
CS
Duan
Y P
YP
D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019328:Buthionine Sulfoximine / Q000633:toxicity*; D002386:Cataract / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000633:toxicity; D016166:Free Radical Scavengers / Q000494:pharmacology; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors
D000975:Antioxidants; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D008315:Malondialdehyde; D019328:Buthionine Sulfoximine; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D008550:Melatonin