Dissertação
Avaliação dos efeitos toxicológicos do composto salicilaldeído-4-feniltiossemicarbazona (SPTS)
Fecha
2015-03-11Autor
Teixeira, Taiane Piccini
Institución
Resumen
The thiosemicarbazone compounds are of considerable scientific interest because of their important
biological and chemical properties, such as antitumor, antibacterial, antiviral, antiprotozoal, cytotoxic,
among others. The compound salicylaldehyde-4-phenylthiosemicarbazone (SPTS), of the class of
thiosemicarbazone, has promising pharmacological activities such as antioxidant and antitumor,
thereby previous studies are needed to evaluate its toxicity. Thus, this study aimed to evaluate the
toxicity in vitroof SPTS compound, through bioassay of Artemia salina in order to determine the
median lethal concentration (LC50), activity of δ-aminolevulinate dehydratase (δ-ALA-D), thiol
oxidase activity and assays of cell viability and genotoxicity. Acute and subacute toxicity tests of
SPTS compound were also performed, using as methodology the Organization's guidelines for
Coordination and Economic Development (OECD guidelines 423 and 407). In the analysis of acute
toxicity, a single dose of 300 and, thereafter, 50 mg/kg SPTS was administered subcutaneously in rats,
to evaluate the estimated mean lethal dose (LD50). In the study of subacute toxicity, SPTS compound
was administered subcutaneously in animals at doses of 5, 10 and 20 mg/kg/day for 14 days.
Biochemical, hematological and oxidative stress parameters were examined in the studies of acute and
sub-acute toxicity, using samples of blood, kidney, liver and brain. Behavioral changes were analyzed
in the subacute toxicity. In the results obtained inin vitroexperiments, was verified a LC50of
69,11μg/ml, being considered a compound active biologically, but there was no thiol oxidase effect or
inhibition of δ-ALA-D. With respect to cell viability and genotoxicity assays, it was found that the
concentration of 100μM significantly decreased cell viability and showed genotoxicity effects against
cell culture. With regard to acute toxicity, the estimated LD50 was of 50-300 mg/kg. Moreover, acute
exposure to 50 mg/kg of SPTS did not cause changes in biochemical and hematological parameters,
but caused an increase in hepatic levels of ascorbic acid. In the assessment of subacute toxicity,
however, numerous changes were observed as an increase in lipid peroxidation and in vitamin C and
non-protein thiols levels in different tissues, as well as changes in glutathione S-transferase and
catalase activities. We also observed behavioral changes in the open field test, decrease in body weight
gain and increased levels of triglycerides. Thus, we conclude that the compound SPTS provided
particularly subacute toxicity, since presented behavioural alterations, as well as changes in oxidative
stress parameters and in the lipid profile.