title: Acute and sub chronic toxicity study of aqueous extract from the leaves and branches of Campomanesia velutina (Cambess) O. Berg.
abstract: BACKGROUND
  Campomanesia velutina leaves and branches infusions are used in Brazilian folk medicine to treat diarrhea and to ameliorate intestinal cramps, respectively.
  
  
  OBJECTIVE
  Carry out the acute and sub chronic pre-clinical evaluation and thus assess the safety and toxicological potential of the specie.
  
  
  METHODS
  In vivo toxicity was evaluated by acute and sub chronic toxicity assays conducted according to the guidelines of the Brazilian Agency of National Health Surveillance (Agência Nacional de Vigilância Sanitária - ANVISA). For acute toxicity evaluation, a single dose of aqueous extracts from the leaves (AEL) and branches (AEB) of Campomanesia velutina were orally administered to mice at doses of 300, 600 and 1200mg/kg. Then, the animals were observed for 14 days. In the sub chronic study, the extracts were orally administered to mice for 14 days at doses of 300, 600 and 1200mg/kg. To assess the toxicological effects, animals were closely observed on general behavior, clinical signs of toxicity, body weight, food and water intake. At the end of the experiment, it was performed biochemical and hematological evaluations, as well as histopathological analysis from the following organs: brain, heart, lungs, liver, stomach, small intestine (section) and left kidney. Preliminary phytochemical analysis was performed using thin layer chromatography (TLC) and colorimetric pharmacognostic tests.
  
  
  RESULTS
  In oral acute assay, treatment with AEB at the major dose (1200mg/kg) caused diarrhea, abdominal cramps and tremors in females. These effects were reversed at 4th hour. Normochromic normocytic anemia was observed in males treated with AEL 300mg/kg and AEB 600 and 1200mg/kg as well as in females treated with AEB 300 and 1200mg/kg. The kidney of all treated animals showed moderate inflammation and a few hemorrhagic points. In sub chronic assay, treatment with AEL 600mg/kg, AEL 1200mg/kg and AEB 1200mg/kg caused hyper excitability in females that was not reversed. Treatments also had impact on weight gain and the relative weight of males' brain was increased on group treated with AEL 300mg/kg, AEB 300 and AEB 1200mg/kg. Although changes in hematological parameters were not observed, serum creatinine levels were significantly higher in males treated with AEB 300mg/kg. Besides, the heart of all treated animals showed intense hyperemia. Preliminary phytochemical analysis revealed the presence of flavonoids, tannins and phenolic compounds.
  
  
  CONCLUSIONS
  Toxicity signs were mainly observed after treatment with AEL and AEB at the two highest tested doses (600 and 1200mg/kg), suggesting that the extracts are relatively safe at its effective dose (300mg/kg). However, alterations on hematological and biochemical parameters and on the kidney and heart of the animals were not closely related with the dose, implying caution on its use.
authors.affiliation: Laboratory of Medicinal Plants, School of Pharmacy, Federal University of Ouro Preto,, Minas Gerais state, Brazil.
authors.forename: Marcela Carolina de Paula Michel
authors.initials: MC
authors.lastname: Araújo
authors.affiliation: Laboratory of Experimental Pharmacology, School of Pharmacy, Federal University of Ouro Preto, Minas Gerais state, Brazil.
authors.forename: Neila Márcia Silva
authors.initials: NM
authors.lastname: Barcellos
authors.affiliation: Laboratory of Morfopathology, Department of Biological Sciences, Federal University of Ouro Preto, Minas Gerais state, Brazil.
authors.forename: Paula Melo de Abreu
authors.initials: PM
authors.lastname: Vieira
authors.affiliation: Laboratory of Medicinal Plants, School of Pharmacy, Federal University of Ouro Preto,, Minas Gerais state, Brazil.
authors.forename: Thiago Magalhães
authors.initials: TM
authors.lastname: Gouveia
authors.affiliation: Centro de Biologia da Reprodução. Universidade Federal de Juiz de Fora, Minas Gerais state, Brazil.
authors.forename: Martha Oliveira
authors.initials: MO
authors.lastname: Guerra
authors.affiliation: Centro de Biologia da Reprodução. Universidade Federal de Juiz de Fora, Minas Gerais state, Brazil.
authors.forename: Vera Maria
authors.initials: VM
authors.lastname: Peters
authors.affiliation: Laboratory of Medicinal Plants, School of Pharmacy, Federal University of Ouro Preto,, Minas Gerais state, Brazil. Electronic address: saudeguima@gmail.com.
authors.forename: Dênia Antunes
authors.initials: DA
authors.lastname: Saúde-Guimarães
mesh_terms: D000818:Animals; D005260:Female; D006321:Heart / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D027822:Myrtaceae; D010936:Plant Extracts / Q000633:toxicity*; D018515:Plant Leaves; D018547:Plant Stems; D023382:Toxicity Tests, Acute; D059550:Toxicity Tests, Subchronic
chemical_list: D010936:Plant Extracts
keywords: Campomanesia velutina; in vivo acute toxicity; in vivo sub chronic toxicity