Modulation of cortical nitric oxide synthase, glutamate, and redox state by nifedipine and taurine in PTZ-kindled mice.
OBJECTIVE
Correlation between pentylenetetrazol (PTZ)-induced kindling and the cortical nitric oxide synthase (NOS), intracellular calcium [Ca2+]i, glutamate, and free radicals was studied in mice, as well as the modulatory action of nifedipine and taurine on these parameters.


METHODS
Male Swiss albino mice were used. Mice in one group received a single convulsive dose of PTZ (50 mg/kg, i.p), and were killed 24 h later. To induce kindling, PTZ was injected in a subconvulsive dose (40 mg/kg, i.p.) every other day for 3 weeks. One kindled group was used as control, whereas two other groups were injected 30 min before PTZ with either nifedipine (30 mg/kg, i.p) or taurine (100 mg/kg, i.p). All three kindled groups were killed 24 h after the last injection.


RESULTS
Compared with normal control group, PTZ-kindled mice had significantly higher levels of [Ca2+]i, malonaldehyde (MDA), NOS, and lactate dehydrogenase (LDH) but had lower levels of superoxide dismutase (SOD) and reduced glutathione (GSH). Acute seizures of the same intensity did not induce these alterations, indicating their link to the kindling phenomenon and not to seizure activity. The effect of taurine, known as an antioxidant, was more pronounced than that of the Ca2+-channel blocker, nifedipine. The first drug reversed the PTZ-kindled action on [Ca2+]i, NOS, LDH, GSH, and SOD, whereas nifedipine restored only LDH and GSH levels. However, both drugs did not restore the elevated MDA level.


CONCLUSIONS
This study suggests that free radicals, as well as NOS, are implicated in PTZ-induced kindling, and that antioxidants could play a role in controlling the accompanying changes.
El-Abhar
Hanan S
HS
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt. Hanabhar@yahoo.com
El Gawad
Hanan M Abd
HM
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000139:chemically induced* / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism; D005971:Glutamates / Q000187:drug effects / Q000378:metabolism; D007696:Kindling, Neurologic / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D009543:Nifedipine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010433:Pentylenetetrazole; D013654:Taurine / Q000494:pharmacology*
D000927:Anticonvulsants; D000975:Antioxidants; D002121:Calcium Channel Blockers; D005609:Free Radicals; D005971:Glutamates; D013654:Taurine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D009543:Nifedipine; D002118:Calcium; D010433:Pentylenetetrazole