Zonisamide Reduces the Increase in 8‐Hydroxy‐2′‐Deoxyguanosine Levels Formed During Iron‐Induced Epileptogenesis in the Brains of Rats

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Abstract
Summary: Purpose: 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. Method: 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.