The protective effect of auraptene against oxidative stress and pentylenetetrazol-induced chemical kindling in mice

Document Type: Research article

Authors

1 Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

2 Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

3 Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

4 Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

5 Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Abstract

It is believed that some pitfalls in the treatment of epilepsy including serious side effects of medications and drug resistance may be resolved by natural compounds. Auraptene is a natural coumarin that is found in many plants, particularly citrus peel. We hypothesized that auraptene might have anticonvulsant properties. Kindling was induced by repeated intraperitoneal (IP) injections of pentylenetetrazol (PTZ, 35 mg/kg) with two-day intervals for 24 days in male mice. Three groups received IP injections of auraptene (12.5, 25, and 50 mg/kg). Three control groups received vehicle, diazepam (3 mg/kg, IP), and vitamin E (150 mg/kg, IP). Seizure-related behaviors were recorded for 30 min after PTZ injection. Moreover, malondialdehyde and reduced glutathione (GSH) were measured in the brain. The results indicated that auraptene at the dose of 12.5 mg/kg and vitamin E prolonged the latency to stage 2 of seizures (P< 0.01). Auraptene at the doses of 25 mg/kg and 50 mg/kg, prolonged the latency to stage 4 (P< 0.01) and reduced stage 5 duration of seizures (P< 0.01). All doses of auraptene reduced median of seizure scores (P< 0.01). The kindled control group had MDA levels similar to intact animals but had a lower concentration of GSH (P< 0.001). None of the tested compounds changed the malondialdehyde concentration significantly. However, auraptene at the dose of 50 mg/kg and vitamin E increased GSH levels (P< 0.05). The results suggested that auraptene had anticonvulsant effects in PTZ-induced chemical kindling that was mediated by mechanisms other than the antioxidant effect of auraptene.

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