PUBLICATION
Toxicological in vitro and subchronic evaluation of LASSBio-596
- Authors
- Araujo, G.L., Vieira, A.E., Barreiro, E.J., Lima, L.M., Cardoso, C.N., Emiliano, N.F., Martins, M.T., Souza, S.S., De Souza, A.M., Berto, C., Costa, M.L., Campos, L.M., França, F.D., Tagliati, C.A.
- ID
- ZDB-PUB-140821-5
- Date
- 2014
- Source
- Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 73: 148-56 (Review)
- Registered Authors
- Costa, Manoel Luis
- Keywords
- Cardiac damage, Preclinical toxicity, Rat, Zebrafish, in vitro
- MeSH Terms
-
- Animals
- Cell Line
- In Vitro Techniques
- Phthalic Acids/toxicity*
- Sulfonamides/toxicity*
- Toxicity Tests, Subchronic*
- Zebrafish
- PubMed
- 25139121 Full text @ Food Chem. Toxicol.
Citation
Araujo, G.L., Vieira, A.E., Barreiro, E.J., Lima, L.M., Cardoso, C.N., Emiliano, N.F., Martins, M.T., Souza, S.S., De Souza, A.M., Berto, C., Costa, M.L., Campos, L.M., França, F.D., Tagliati, C.A. (2014) Toxicological in vitro and subchronic evaluation of LASSBio-596. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 73:148-56.
Abstract
LASSBio-596, 2-[4-(1,4-tiazinan-4-ylsulfonyl) phenylcarbamoyl] benzoic acid, is an achiral compound containing a subunit carboxylic amide, was capable of preventing induced mechanical and morphological changes in the lungs that commonly caused the onset of asthma. Previous studies to determine the acute toxicity of oral LASSBio-596 at dose of 2000 mg/kg caused no deaths in any of the tested animals. To further evaluate the safety of LASSBio-596, in vitro and in vivo tests were carried out. Regarding to in vitro test were used renal, hepatic, pulmonary, cardiac, neurologic and intestinal cell lines. They were evaluated using neutral red (NR) and [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assays. Micronuclei also was performed. Concerning to in vivo was performed subchronic on Wistar rats at doses of 10, 50, and 250 mg/kg and zebrafish test. The in vitro tests results showed the safety of LASSBio-596. However, subchronic toxicity study results revealed changes in the blood parameters of amylase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose and creatine kinase (CK) which is used for cardiotoxicity evaluation, although, did not identify any histopathological alterations. However, zebrafish test demonstrated cardiac damage. It was impossible to estimate the no-observed-adverse-effect-levels and lowestobserved-adverse-effect level due to the presence of cardiotoxicity in all tested doses.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping