title: Antiepileptogenic, antioxidant and genotoxic evaluation of rosmarinic acid and its metabolite caffeic acid in mice.
abstract: OBJECTIVE
  Antioxidant compounds have been extensively investigated as a pharmacological alternatives to prevent epileptogenesis. Rosmarinic acid (RA) and caffeic acid (CA) are compounds with antioxidant properties, and RA has been shown to inhibit GABA transaminase activity (in vitro). Our aim was to evaluate the effect of RA and CA on seizures induced by pentylenotetrazole (PTZ) using the kindling model in mice.
  
  
  METHODS
  Male CF-1 mice were treated once every three days during 16days with RA (1, 2 or 4mg/kg; i.p.), or CA (1, 4 or 8mg/kg; i.p.), or positive controls diazepam (1mg/kg; i.p.) or vigabatrin (600mg/kg; p.o.), 30min before PTZ administration (50mg/kg; s.c.). After the last treatment, animals were sacrificed and the cortex was collected to evaluate free radicals (determined by 2',7'-dichlorofluorescein diacetate probe), superoxide dismutase (SOD) and genotoxic activity (Alkaline Comet Assay).
  
  
  RESULTS
  Rosmarinic acid 2mg/kg increased latency and decreased percentage of seizures, only on the 4th day of observation. The other tested doses of RA and CA did not show any effect. Rosmarinic acid 1mg/kg, CA 4mg/kg and CA 8mg/kg decreased free radicals, but no dose altered the levels of enzyme SOD. In the comet assay, RA 4mg/kg and CA 4mg/kg reduced the DNA damage index.
  
  
  CONCLUSIONS
  Some doses of rosmarinic acid and CA tested showed neuroprotective action against oxidative and DNA damage produced in the kindling epilepsy model, although they did not produce antiepileptogenic effect in vivo.
authors.affiliation: Laboratório de Neurofarmacologia e Toxicologia Pré-Clínica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Vanessa Rodrigues
authors.initials: VR
authors.lastname: Coelho
authors.affiliation: Laboratório de Neurofarmacologia e Toxicologia Pré-Clínica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Caroline Gonçalves
authors.initials: CG
authors.lastname: Vieira
authors.affiliation: Laboratório de Neurofarmacologia e Toxicologia Pré-Clínica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Luana Pereira
authors.initials: LP
authors.lastname: de Souza
authors.affiliation: Laboratório de Neuropsicofarmacologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Felipe
authors.initials: F
authors.lastname: Moysés
authors.affiliation: Laboratório de Neuropsicofarmacologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Carla
authors.initials: C
authors.lastname: Basso
authors.affiliation: Laboratório de Genética Toxicológica, Universidade Luterana do Brasil, Canoas, RS, Brazil.
authors.forename: Débora Kuck Mausolff
authors.initials: DK
authors.lastname: Papke
authors.affiliation: Laboratório de Genética Toxicológica, Universidade Luterana do Brasil, Canoas, RS, Brazil.
authors.forename: Thienne Rocha
authors.initials: TR
authors.lastname: Pires
authors.affiliation: Laboratório de Neuropsicofarmacologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Ionara Rodrigues
authors.initials: IR
authors.lastname: Siqueira
authors.affiliation: Laboratório de Genética Toxicológica, Universidade Luterana do Brasil, Canoas, RS, Brazil.
authors.forename: Jaqueline Nascimento
authors.initials: JN
authors.lastname: Picada
authors.affiliation: Laboratório de Neurofarmacologia e Toxicologia Pré-Clínica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: patipere@yahoo.com.br.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Pereira
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D002109:Caffeic Acids / Q000494:pharmacology*; D002478:Cells, Cultured; D002934:Cinnamates / Q000494:pharmacology*; D020552:Comet Assay; D003292:Convulsants / Q000633:toxicity; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics*; D053630:Depsides / Q000494:pharmacology*; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D010433:Pentylenetetrazole / Q000633:toxicity; D013482:Superoxide Dismutase / Q000378:metabolism; D000097123:Rosmarinic Acid
chemical_list: D000927:Anticonvulsants; D000975:Antioxidants; D002109:Caffeic Acids; D002934:Cinnamates; D003292:Convulsants; D053630:Depsides; D010433:Pentylenetetrazole; D013482:Superoxide Dismutase; D000097123:Rosmarinic Acid; C040048:caffeic acid
keywords: Caffeic acid; Comet assay; Kindling; Oxidative stress; Pentylenetetrazole; Rosmarinic acid