title: The effects of coenzyme Q10 on seizures in mice: the involvement of nitric oxide.
abstract: Coenzyme Q10 is a potent antioxidant in both mitochondria and lipid membranes. It has also been recognized to have an effect on gene expression. This study was designed to investigate whether acute or subchronic treatment with coenzyme Q10 altered the seizures induced by pentylenetetrazole or electroshock in mice. We also evaluated the involvement of nitric oxide in the effects of coenzyme Q10 in pentylenetetrazole-induced seizure models. Acute oral treatment with different doses of coenzyme Q10 did not affect the seizure in intraperitoneal pentylenetetrazole, intravenous pentylenetetrazole, and electroshock models in mice. Subchronic oral administration of coenzyme Q10 (100 mg/kg or more) increased time latencies to the onset of myoclonic jerks and clonic seizures induced by intraperitoneal pentylenetetrazole and at the doses of 25 mg/kg or more increased the seizure threshold induced by intravenous infusion of pentylenetetrazole. Subchronic doses of coenzyme Q10 (50 mg/kg or more) also decreased the incidence of tonic seizures in the electroshock-induced seizure model. Moreover, acute treatment with the precursor of nitric oxide synthesis, L-arginine (60 mg/kg), led to a significant potentiation of the antiseizure effects of subchronic administration of coenzyme Q10 (400 mg/kg in intraperitoneal and 6.25 mg/kg in intravenous pentylenetetrazole tests). Acute treatment with l-NAME (5 mg/kg), a nonspecific nitric oxide synthase inhibitor, significantly attenuated the antiseizure effects of subchronic doses of coenzyme Q10 in both seizure models induced by pentylenetetrazole. On the other hand, acute administration of aminoguanidine (100 mg/kg), a specific inducible nitric oxide synthase inhibitor, did not affect the seizures in mice treated with subchronic doses of coenzyme Q10 in both intraperitoneal and intravenous pentylenetetrazole tests. In conclusion, only subchronic and not acute administration of coenzyme Q10 attenuated seizures induced by pentylenetetrazole or electroshock. We also demonstrated, for the first time, the interaction between nitric oxide and coenzyme Q10 in antiseizure activity probably through the induction of constitutive nitric oxide synthase.
authors: Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
authors: Elahe
authors: E
authors: Sattarinezhad
authors: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran.
authors: Hamed
authors: H
authors: Shafaroodi
authors: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran.
authors: Kiandokht
authors: K
authors: Sheikhnouri
authors: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran.
authors: Zahra
authors: Z
authors: Mousavi
authors: Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: moezile@yahoo.com.
authors: Leila
authors: L
authors: Moezi
mesh_terms: D000818:Animals; D001120:Arginine / Q000008:administration & dosage; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D004597:Electroshock / Q000009:adverse effects; D004830:Epilepsy, Tonic-Clonic / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D006146:Guanidines / Q000008:administration & dosage; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology / Q000627:therapeutic use; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000008:administration & dosage; D010433:Pentylenetetrazole / Q000009:adverse effects / Q000633:toxicity; D012640:Seizures / Q000188:drug therapy; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D006146:Guanidines; D014451:Ubiquinone; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; C024989:coenzyme Q10; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester; D010433:Pentylenetetrazole
keywords: Coenzyme Q10; Electroshock; Mice; Nitric oxide; Pentylenetetrazole; Seizure