Araujo G.L.,Instituto Nacional Of Ciencia E Tecnologia Of Farmacos E Medicamentos Inct Inofar |
Vieira A.E.D.,Instituto Nacional Of Ciencia E Tecnologia Of Farmacos E Medicamentos Inct Inofar |
Barreiro E.J.,Instituto Nacional Of Ciencia E Tecnologia Of Farmacos E Medicamentos Inct Inofar |
Lima L.M.,Instituto Nacional Of Ciencia E Tecnologia Of Farmacos E Medicamentos Inct Inofar |
And 10 more authors.
Food and Chemical Toxicology | Year: 2014
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 lowest observed-adverse-effect level due to the presence of cardiotoxicity in all tested doses. © 2014 Elsevier Ltd.