Avaliação dos efeitos toxicológicos do composto salicilaldeído-4-feniltiossemicarbazona (SPTS)

Abstract

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.