Abstract
Purpose: The pleiotropic effects of statins (antioxidant and
anti-inflammation) have been reported by previous studies. Therefore, we aimed
to determine whether pitavastatin has protective effects against
pentylenetetrazol (PTZ)-induced kindling in mice and also whether pitavastatin
improves the brain antioxidant capacity and attenuates the oxidative injuries
in kindled mice.
Methods: Twenty-four mice were randomly divided into four
groups (each group n=6); control, PTZ-kindling and PTZ-kindled rats treated
with pitavastatin (1&4 mg/kg). PTZ kindling seizures were induced by
repetitive intraperitoneal injections of PTZ (65 mg/kg) every 48 hours till day
twenty-one. Animals received daily oral pitavastatin for twenty-one days.
Latency, score and duration of the seizures were recorded. The activities of
catalase (CAT) ad superoxide dismutase (SOD), and likewise the contents of
malondialdehyde (MDA) and nitrate were assessed in the brains of all rats.
Results: There was a progressive reduction in latency of the
kindled rats in the next injections of PTZ. Pitavastatin reduced this value
(latency) particularly at higher dose. Seizures duration and score also
decreased in treatment groups. SOD and CAT activities significantly decreased
in PTZ-kindling group by 62% and 64%, respectively, but pitavastatin did not
significantly change the SOD and CAT activities. Brain MDA and nitrate
significantly increased in PTZ-kindling group by 53% and 30%, respectively.
Pitavastatin at higher dose significantly decreased the MDA and nitrate
contents of PTZ-kindling rats by 45% and 32%, respectively.
Conclusion: Our findings revealed that pitavastatin can improve
the behavioral expression of the PTZ-kindling rats and attenuate the
seizure-induced oxidative/nitrosative damage.