Zonisamide reduces the increase in 8-hydroxy-2'-deoxyguanosine levels formed during iron-induced epileptogenesis in the brains of rats.
OBJECTIVE
To examine the change of 8-hydroxy-2'deoxyguanosine (8-OHdG) levels, which are used as a marker for oxidative DNA damage, in iron-induced epileptogenic foci of the rat cerebrum.


METHODS
Male Wistar rats were given a cortical injection of ferric chloride, and their 8-OHdG levels were determined over time. Additional animals were pretreated with the antiepileptic drug zonisamide (ZNS) before the ferric chloride injection, and their 8-OHdG levels were compared with the nonpretreated rats.


RESULTS
Fifteen minutes after ferric chloride solution injection, the level of 8-OHdG increased, reaching a maximum 30 minutes after injection. Sixty minutes after injection, the levels coincided with those of controls. ZNS, in concentrations of 50 and 100 mg/kg body weight, prevented the increase of 8-OHdG levels within the cerebrum 30 minutes after iron solution injection.


CONCLUSIONS
These results indicate that the formation of iron-induced epileptogenic foci in rats is related to DNA-damage-induced reactive oxygen species and that the inhibition of 8-OHdG formation by ZNS after iron injection may be due to the drug's antioxidant activity. The data suggest that free radical species known to be formed during iron salts-induced focal epileptogenesis cause damage to isocortical DNA. Furthermore, ZNS appears to inhibit the focal injuring response to DNA that occurs following iron salts-induced acute epileptogenesis.
Komatsu
M
M
Institute for Life Support Technology, Yamagata Technopolis Foundation, Matsuei, Japan.
Hiramatsu
M
M
Willmore
L J
LJ
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D001923:Brain Chemistry / Q000187:drug effects; D002540:Cerebral Cortex / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D002712:Chlorides; D004249:DNA Damage / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D004827:Epilepsy / Q000139:chemically induced* / Q000378:metabolism*; D005290:Ferric Compounds / Q000008:administration & dosage; D007555:Isoxazoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D000078305:Zonisamide
D000927:Anticonvulsants; D002712:Chlorides; D005290:Ferric Compounds; D007555:Isoxazoles; D017382:Reactive Oxygen Species; D000078305:Zonisamide; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; C024555:ferric chloride