DNA damage and oxidative stress induced by seizures are decreased by anticonvulsant and neuroprotective effects of lobeline, a candidate to treat alcoholism.

The alkaloid lobeline (Lob) has been studied due to its potential use in treatment of drug abuse. This study evaluates the possible anticonvulsant and neuroprotective activities of Lob to obtain new information on its properties that could confirm it as a candidate in the treatment of alcohol addiction. The anticonvulsant effect of Lob was evaluated using a pilocarpine-induced seizure model. In addition, possible neuroprotective effects were investigated measuring DNA damage using the comet assay, assessing free radical levels by dichlorofluorescein diacetate (DCF) oxidation, and measuring the antioxidant potential using the α, α-diphenyl-ß-picrylhydrazyl (DPPH) scavenging assay, besides measuring superoxide dismutase (SOD) and catalase (CAT) enzyme activities in brain tissues. Lobeline increased the latency to the first seizure and decreased the percentage of seizures in a similar way as diazepam, used as control. DNA damage induced by Pil and hydrogen peroxide were decreased in hippocampus and cerebral cortex from mice treated with Lob. The levels of free radicals and CAT activity increased in cortex and hippocampus, respectively, in mice treated with Pil. Lobeline decreased CAT in hippocampus, leading to similar values as in the saline negative control. In conclusion, Lob has anticonvulsant and neuroprotective actions that may be mediated by antioxidant-like mechanisms, indicating its potential as candidate drug in alcoholism therapy.

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

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.