title: Acute toxicity and long-term safety evaluation of the crude extract from rhizomes of Limonium brasiliense in mice and rats.
abstract: BACKGROUND
  Limonium brasiliense (Boiss.) Kuntze, Plumbaginaceae, popularly known as baicuru, has been used in folk medicine to treat menstrual cramps and to regulate menstrual periods. However, little is known about its safety. This study evaluated the safety through in vivo tests of the acute, long-term, and liver toxicity, and the mutagenicity of the crude extract (CE) from rhizomes of L. brasiliense.
  
  
  METHODS
  The acute toxicity was assessed in Swiss mice, and the chronic toxicity in Wistar rats. Male and female mice received the CE orally in single doses of 1.0, 2.0, 3.0, 4.0, or 5.0 g/kg. Clinical changes and mortality rate were used as parameters to assess the acute toxicity. In the long-term evaluation, male and female Wistar rats were treated orally with daily doses of the CE (50, 100, or 200 mg/kg) for 90 days. Assessments of weight, behavior and food intake, urinalysis, biochemical and hematological analyses, as well as macro- and microscopic observations of several organs were performed. The redox state of the liver was evaluated as a means of investigating the liver toxicity, and the micronucleus test to assess mutagenicity was also performed.
  
  
  RESULTS
  Evaluation of acute toxicity indicated no apparent clinical change in the animals; the LD50 was 4.8 g/kg. Evaluation after 90 days administration showed that the CE, even in higher doses than are considered therapeutic, appeared to be safe. The micronucleus test demonstrated a low mutagenic potential for the CE.
  
  
  CONCLUSIONS
  Our results showed that treatment with the CE from L. brasiliense caused low or no toxicity, as assessed using these doses and evaluation methods.
authors: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Maringá, PR, Brazil.
authors: Tânia M
authors: TM
authors: Antonelli-Ushirobira
authors: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Maringá, PR, Brazil.
authors: Andressa
authors: A
authors: Blainski
authors: Departamento de Medicina, Universidade Estadual de Maringá, Maringá, Brazil.
authors: Henrique G
authors: HG
authors: Fernandes
authors: Departamento de Farmácia, Universidade Estadual de Maringá, Avenida Colombo, 5790, BR-87020-900, Maringá, PR, Brazil.
authors: Gislaine F
authors: GF
authors: Moura-Costa
authors: Departamento de Farmácia, Universidade Estadual de Maringá, Avenida Colombo, 5790, BR-87020-900, Maringá, PR, Brazil.
authors: Marco A
authors: MA
authors: Costa
authors: Departamento de Ciências Fisiológicas, Universidade Estadual de Maringá, PR, Brazil.
authors: Lilian B
authors: LB
authors: Campos-Shimada
authors: Departamento de Ciências Fisiológicas, Universidade Estadual de Maringá, PR, Brazil.
authors: Clairce L
authors: CL
authors: Salgueiro-Pagadigorria
authors: Departamento de Medicina, Universidade Estadual de Maringá, Maringá, Brazil.
authors: Edilson N
authors: EN
authors: Kaneshima
authors: Departamento de Análises Clínicas e Biomedicina, Universidade Estadual de Maringá, Maringá, PR, Brazil.
authors: Tânia C A
authors: TC
authors: Becker
authors: Departamento de Ciências Morfológicas, Universidade Estadual de Maringá, Maringá, PR, Brazil.
authors: Eneri V S
authors: EV
authors: Leite-Mello
authors: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Maringá, PR, Brazil; Departamento de Farmácia, Universidade Estadual de Maringá, Avenida Colombo, 5790, BR-87020-900, Maringá, PR, Brazil. Electronic address: mello@uem.br.
authors: João C P de
authors: JC
authors: Mello
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000302:isolation & purification / Q000633:toxicity*; D029606:Plumbaginaceae; D051381:Rats; D017208:Rats, Wistar; D027343:Rhizome / Q000633:toxicity*; D023382:Toxicity Tests, Acute / Q000379:methods*; D036401:Toxicity Tests, Chronic / Q000379:methods*
chemical_list: D010936:Plant Extracts
keywords: Limonium brasiliense; Mutagenicity; Plumbaginaceae; Preclinical toxicity; Redox state of the liver