  Pricila Pflüger 1 , Gabriela Gregory Regner 1 , Vanessa Rodrigues Coelho 1 , Lucas Lima da Silva 1 , Leopoldo Nascimento 2 , Cassiana Macagnan Viau 3 , Régis Adriel Zanette 1 , Cleonice Hoffmann 3 , Jaqueline Nascimento Picada 3 , Jenifer Saffi 2 and Patrícia Pereira 1,* 1 Laboratory of Neuropharmacology and Preclinical Toxicology, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil; 2 Department of Basic Health Sciences, Laboratory of Genetic Toxicology, UFCSPA, Porto Alegre, RS, Bra- zil and 3 Laboratory of Genetic Toxicology, Lutheran University of Brazil, Canoas, RS, Brazil Abstract: Background and Objective: Gamma-decanolactone (GD) is a monoterpene effective against seizures induced by pentylenetetrazole. The mechanism of action of GD is likely to be via glu- tamate antagonism. GD also inhibits intracellular reactive oxygen species (ROS) generation and the lipopolysaccharide-induced expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-α) in vitro. Considering the neuropharmacological profile of GD studied so far, we investigated the effect of intraperitoneal administration of GD 100 and 300 mg/kg on pilocarpine (PIL)-induced status epilepticus (SE) in mice. Methods: GD was administered 30 min before PIL. Behavioral (latency to first seizure and the per- centage of clonic forelimb seizures), biochemical, and oxidative stress parameters were evaluated. DNA damage in the cerebral cortex of mice was assessed using the comet assay and mutagenic activi- ty of GD was evaluated using Salmonella/microsome assay in TA100, TA98, TA97a, TA102, and TA1535 strains, with and without metabolic activation (S9 mix). Results: The behavioral results showed that only the latency to the first clonic seizure increased in the groups treated with GD 300 mg/kg, but not when the animals received GD 100 mg/kg. Both GD dos- es were able to increase superoxide dismutase and catalase activities, inducing a decrease in ROS and nitrite production and in DNA damage in the cerebral cortex. GD was not able to induce base pair substitution and frameshift mutations in the absence or in the presence of metabolic activation. Conclusion: These findings demonstrate that GD does not improve behavioral parameters in the PIL model, but it was able to protect seizure-related oxidative stress and DNA damage in mice, without inducing gene mutations. A R T I C L E H I S T O R Y Received: July 07, 2017 Revised: September 09, 2017 Accepted: September 18, 2017 DOI: 10.2174/1874467210666171002114954 Keywords: Gamma-decanolactone, genotoxicity, mutagenicity, oxidative stress, pilocarpine, status epilepticus. 1. INTRODUCTION Epilepsy is a brain function disorder characterized by un- predictable and recurrent seizures. Its prevalence in the gen- eral population is approximately 1% [1, 2] affecting at least 70 million people worldwide [2, 3]. Importantly, temporal dysfunction of neurons culminates in clinical manifestations such as epileptic seizures [4]. *Address correspondence to this author at the Laboratory of Neuropharma- cology and Preclinical Toxicology, Department of Pharmacology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Sarmen- to Leite 500/305, 90050-170 Porto Alegre, Brazil; Tel/Fax: +55 51 33083121; E-mail: patriciapereira@ufrgs.br Approximately, 30% of epileptic patients have temporal lobe epilepsy (TLE), which manifests as the progressive de- velopment of complex partial seizures, hippocampal neuro- degeneration, and co-morbidities such as cognitive and mood impairments [5, 6]. The therapeutic strategies used to treat epilepsy actually only treat the symptoms, and have often proven ineffective [7]. Although there are more than 20 an- tiepileptic drugs (AEDs) currently available, about one-third of patients present drug resistance or adverse effects, and are more likely to become refractory to pharmacological treat- ment [8]. Oxidative stress is described as an imbalance between generation and elimination of reactive oxygen species (ROS) and reactive nitrogen species (RNS) [9]. Excess of free radi- Send Orders for Reprints to reprints@benthamscience.ae 162 Current Molecular Pharmacology, 2018, 11, 162-169 RESEARCH ARTICLE Gamma-Decanolactone Improves Biochemical Parameters Associated with Pilocarpine-Induced Seizures in Male Mice 1874-4702/18 $58.00+.00 © 2018 Bentham Science Publishers Current Molecular Pharmacology