title: Behavioral and genotoxic evaluation of rosmarinic and caffeic acid in acute seizure models induced by pentylenetetrazole and pilocarpine in mice.
abstract: The goal of this study was to investigate the effects of rosmarinic acid (RA) and caffeic acid (CA) in the acute pentylenetetrazole (PTZ) and pilocarpine (PIL) seizure models. We also evaluated the effect of RA and CA on the diazepam (DZP)-induced sleeping time test and its possible neuroprotective effect against the genotoxic damage induced by PTZ and PIL. Mice were treated intraperitoneally (i.p.) with saline, RA (2 or 4 mg/kg), or CA (4 or 8 mg/kg) alone or associated to low-dose DZP. After, mice received a single dose of PTZ (88 mg/kg) or PIL (250 mg/kg) and were monitored for the percentage of seizures and the latency to first seizure (LFS) >3 s. Vigabatrin and DZP were used as positive controls. In the DZP-induced sleeping time test, mice were treated with RA and CA and 30 min after receiving DZP (25 mg/kg, i.p.). The alkaline comet assay was performed after acute seizure tests to evaluate the antigenotoxic profiles of RA and CA. The doses of RA and CA tested alone did not reduce the occurrence of seizures induced by PTZ or PIL. The association of 4 mg/kg RA + low-dose DZP was shown to increase LFS in the PTZ model, compared to the group that received only the DZP. In the DZP-induced sleeping time test, the latency to sleep was reduced by 4 mg/kg RA and 8 mg/kg CA. The PTZ-induced genotoxic damage was not prevented by RA or CA, but the PIL-induced genotoxic damage was decreased by pretreatment with 4 mg/kg RA (in cortex) and 4 mg/kg CA (in hippocampus). In conclusion, RA and CA presented neuroprotective effect against PIL-induced genotoxic damage and reduced the latency to DZP-induced sleep. Of the rosmarinic acid, 4 mg/kg enhanced the DZP effect in the increase of latency to clonic PTZ-induced seizures.
authors.affiliation: Laboratory of Neuropharmacology and Preclinical Toxicology, Department of Pharmacology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Sarmento Leite 500/305, Porto Alegre, RS, CEP 90050-170, Brazil.
authors.forename: Vanessa Rodrigues
authors.initials: VR
authors.lastname: Coelho
authors.affiliation: Laboratory of Neuropharmacology and Preclinical Toxicology, Department of Pharmacology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Sarmento Leite 500/305, Porto Alegre, RS, CEP 90050-170, Brazil.
authors.forename: Caroline Gonçalves
authors.initials: CG
authors.lastname: Vieira
authors.affiliation: Laboratory of Neuropharmacology and Preclinical Toxicology, Department of Pharmacology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Sarmento Leite 500/305, Porto Alegre, RS, CEP 90050-170, Brazil.
authors.forename: Luana Pereira
authors.initials: LP
authors.lastname: de Souza
authors.affiliation: Laboratory of Neuropharmacology and Preclinical Toxicology, Department of Pharmacology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Sarmento Leite 500/305, Porto Alegre, RS, CEP 90050-170, Brazil.
authors.forename: Lucas Lima
authors.initials: LL
authors.lastname: da Silva
authors.affiliation: Laboratory of Neuropharmacology and Preclinical Toxicology, Department of Pharmacology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Sarmento Leite 500/305, Porto Alegre, RS, CEP 90050-170, Brazil.
authors.forename: Pricila
authors.initials: P
authors.lastname: Pflüger
authors.affiliation: Laboratory of Neuropharmacology and Preclinical Toxicology, Department of Pharmacology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Sarmento Leite 500/305, Porto Alegre, RS, CEP 90050-170, Brazil.
authors.forename: Gabriela Gregory
authors.initials: GG
authors.lastname: Regner
authors.affiliation: Laboratory of Genetic Toxicology, Lutheran University of Brazil, Av. Farroupilha 8001, Canoas, RS, CEP 92425-900, Brazil.
authors.forename: Débora Kuck Mausolff
authors.initials: DK
authors.lastname: Papke
authors.affiliation: Laboratory of Genetic Toxicology, Lutheran University of Brazil, Av. Farroupilha 8001, Canoas, RS, CEP 92425-900, Brazil.
authors.forename: Jaqueline Nascimento
authors.initials: JN
authors.lastname: Picada
authors.affiliation: Laboratory of Neuropharmacology and Preclinical Toxicology, Department of Pharmacology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Sarmento Leite 500/305, Porto Alegre, RS, CEP 90050-170, Brazil. patipere@yahoo.com.br.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Pereira
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D002109:Caffeic Acids / Q000494:pharmacology*; D002934:Cinnamates / Q000494:pharmacology*; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D053630:Depsides / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010433:Pentylenetetrazole; D010862:Pilocarpine; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control* / Q000523:psychology; D012890:Sleep / Q000187:drug effects*; D013997:Time Factors; D000097123:Rosmarinic Acid
chemical_list: D000927:Anticonvulsants; D002109:Caffeic Acids; D002934:Cinnamates; D053630:Depsides; D003975:Diazepam; D018696:Neuroprotective Agents; D010433:Pentylenetetrazole; D010862:Pilocarpine; D000097123:Rosmarinic Acid; C040048:caffeic acid
keywords: Caffeic acid; Comet assay; Genotoxicity; Pentylenetetrazole; Pilocarpine; Rosmarinic acid