Effect of melatonin on biochemical variables induced by phenytoin in organs of mothers, foetuses and offsprings of rats.
The present pre- and postnatal study was carried out to investigate the effect of melatonin (MEL), a potent antioxidant, on biochemical variables in the in vivo model of intrauterine hypoxia in rats. Chronic hypoxia was induced pharmacologically by the administration of the anticonvulsant phenytoin (PHT) during pregnancy. Rats were orally treated by PHT (150 mg/kg) from day 7 to 18 of gestation. MEL in drinking water (40 microg/ml) was administered from day 0 to 19 of gestation. The activity of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase (NAGA) and the level of glutathione (GSH) were used as markers of tissue damage. In the prenatal study PHT-induced toxic damage was associated with an increase in NAGA activity and decrease of GSH level in placenta and in maternal serum and heart. MEL partially inhibited the changes of NAGA activity given above. MEL was able to increase only the decreased level of GSH in maternal heart. PHT decreased the level of GSH and increased the activity of NAGA in foetal organs, the improvement occurred in the liver and lungs, but not in foetal brain. In the postnatal study a significant increase of liver GSH level was found in all (control, MEL, PHT, MEL+PHT) groups of 1-day-old pups, while the activity of NAGA remained unchanged. We did not observe any significant differences in NAGA activity in the lungs and heart of pups. MEL increased the GSH level in lungs and heart. We concluded that administration of MEL during pregnancy partially inhibited the biochemical changes induced by PHT.
Navarová
J
J
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Slovak Republic. Jana.Navarova@savba.sk
Ujházy
E
E
Dubovický
M
M
Mach
M
M
D000118:Acetylglucosaminidase / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000633:toxicity*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D000860:Hypoxia / Q000139:chemically induced; D008550:Melatonin / Q000494:pharmacology*; D018384:Oxidative Stress; D010672:Phenytoin / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D000927:Anticonvulsants; D010672:Phenytoin; D000118:Acetylglucosaminidase; D005978:Glutathione; D008550:Melatonin