Gamma-Decanolactone Improves Biochemical Parameters Associated with Pilocarpine-Induced Seizures in Male Mice

Title:Gamma-Decanolactone Improves Biochemical Parameters Associated with Pilocarpine-Induced Seizures in Male Mice

Volume: 11

Author(s): Pricila Pfluger, Gabriela Gregory Regner, Vanessa Rodrigues Coelho, Lucas Lima da Silva, Leopoldo Nascimento, Cassiana Macagnan Viau, Regis Adriel Zanette, Cleonice Hoffmann, Jaqueline Nascimento Picada, Jenifer Saffi and Patricia Pereira*

Affiliation:

• Laboratory of Neuropharmacology and Preclinical Toxicology, Federal University of Rio Grande do Sul, Porto Alegre, RS,Brazil

Keywords: Gamma-decanolactone, genotoxicity, mutagenicity, oxidative stress, pilocarpine, status epilepticus.

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 glutamate 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 percentage 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 activity 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 doses 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.

Cite this article as:

Pfluger Pricila , Regner Gregory Gabriela, Coelho Rodrigues Vanessa, da Silva Lima Lucas, Nascimento Leopoldo , Viau Macagnan Cassiana, Zanette Adriel Regis , Hoffmann Cleonice , Picada Nascimento Jaqueline, Saffi Jenifer and Pereira Patricia*, Gamma-Decanolactone Improves Biochemical Parameters Associated with Pilocarpine-Induced Seizures in Male Mice, Current Molecular Pharmacology 2018; 11 (2) . https://dx.doi.org/10.2174/1874467210666171002114954