title: Evaluation of mutagenic and genotoxic activities of lobeline and its modulation on genomic instability induced by ethanol.
abstract: OBJECTIVE
  Lobeline is a natural alkaloid derived from Lobelia inflata that has been investigated as a clinical candidate for the treatment of alcoholism. In a pre-clinical trial, lobeline decreased the preference for and consumption of ethanol, due to the modulation of the nicotinic acetylcholine receptor. However, the interaction between lobeline and ethanol is poorly known and thus there are safety concerns. The present study was conducted to evaluate the mutagenic and genotoxic effects of lobeline and assess its modulation of ethanol-induced toxicological effects.
  
  
  METHODS
  CF-1 male mice were divided into five groups. Groups received an intraperitoneal injection of saline solution, lobeline (5 or 10mg/kg), ethanol (2.5 g/kg), or lobeline plus ethanol, once a day for three consecutive days. Genotoxicity was evaluated in peripheral blood using the alkaline comet assay. The mutagenicity was evaluated using both Salmonella/microsome assay in TA1535, TA97a, TA98, TA100, and TA102 Salmonella typhimurium strains and the micronucleus test in bone marrow. Possible liver and kidney injuries were evaluated using biochemical analysis.
  
  
  RESULTS
  Lobeline did not show genotoxic or mutagenic effects and did not increase the ethanol-induced genotoxic effects in blood. Lobeline also protected blood cells against oxidative damage induced by hydrogen peroxide. Biochemical parameters were not altered, indicating no liver or kidney injuries or alterations in lipid and carbohydrate metabolisms.
  
  
  CONCLUSIONS
  These findings suggest that lobeline does not induce gene or chromosomal mutations, and that this lack of genetic toxicity is maintained in the presence of ethanol, providing further evidence of the safety of this drug to treat alcohol dependence.
authors.affiliation: Laboratório de Genética Toxicológica, Universidade Luterana do Brasil, Canoas, RS, Brazil.
authors.forename: Liana Dantas
authors.initials: LD
authors.lastname: da Costa E Silva
authors.affiliation: Laboratório de Genética Toxicológica, Universidade Luterana do Brasil, Canoas, RS, Brazil.
authors.forename: Laise Carla Lima Verde
authors.initials: LC
authors.lastname: Rodrigues
authors.affiliation: Laboratório de Genética Toxicológica, Universidade Luterana do Brasil, Canoas, RS, Brazil.
authors.forename: Viviane Ramos
authors.initials: VR
authors.lastname: Dos Santos
authors.affiliation: Laboratório de Patologia Clínica, Hospital Veterinário, Universidade Luterana do Brasil, Canoas, RS, Brazil.
authors.forename: Mariangela
authors.initials: M
authors.lastname: da Costa Allgayer
authors.affiliation: Laboratório de Fitoquímica, Universidade Luterana do Brasil, Canoas, RS, Brazil.
authors.forename: Alexandre
authors.initials: A
authors.lastname: de Barros Falcão Ferraz
authors.affiliation: Bioensaios Análises e Consultoria Ambiental, Viamão, RS, Brazil.
authors.forename: Helena Campos
authors.initials: HC
authors.lastname: Rolla
authors.affiliation: Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Pereira
authors.affiliation: Laboratório de Genética Toxicológica, Universidade Luterana do Brasil, Canoas, RS, Brazil. Electronic address: jnpicada@cpovo.net.
authors.forename: Jaqueline Nascimento
authors.initials: JN
authors.lastname: Picada
mesh_terms: D000437:Alcoholism / Q000175:diagnosis / Q000188:drug therapy; D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods; D000431:Ethanol / Q000633:toxicity*; D042822:Genomic Instability / Q000187:drug effects* / Q000235:genetics*; D008120:Lobeline / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity*; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests / Q000379:methods; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D011897:Random Allocation
chemical_list: D010936:Plant Extracts; D000431:Ethanol; D008120:Lobeline
keywords: (−)-Lobeline hydrochloride (PubChem CID: 45358761); Addiction; Alcoholism; Ames test; Comet assay; Cyclophosphamide monohydrate (PubChem CID: 22420); ETHANOL (PubChem CID: 702); Genomic; Lobeline; Micronucleus test; Mutagenicity