Evaluation of Toxicity and Oxidative Stress of 2-Acetylpyridine-N(4)-orthochlorophenyl Thiosemicarbazone.

Thiosemicarbazones are well known for their broad spectrum of action, including antitumoral and antiparasitic activities. Thiosemicarbazones work as chelating binders, reacting with metal ions. The objective of this work was to investigate the in silico, in vitro, and in vivo toxicity and oxidative stress of 2-acetylpyridine-N(4)-orthochlorophenyl thiosemicarbazone (TSC01). The in silico prediction showed good absorption by biological membranes and no theoretical toxicity. Also, the compound did not show cytotoxicity against Hep-G2 and HT-29 cells. In the acute nonclinical toxicological test, the animals treated with TSC01 showed behavioral changes of stimulus of the central nervous system (CNS) at 300 mg/kg. One hour after administration, a dose of 2000 mg/kg caused depressive signs. All changes disappeared after 24 h, with no deaths, which suggest an estimated LD50 of 5000 mg/kg and GSH 5. The group treated with 2000 mg/kg had an increase of water consumption and weight gain in the second week. The biochemical parameters presented no toxicity relevance, and the analysis of oxidative stress in the liver found an increase of lipid peroxidation and nitric oxide. However, histopathological analysis showed organ integrity was maintained without any changes. In conclusion, the results show the low toxicological potential of thiosemicarbazone derivative, indicating future safe use.

Non-clinical acute and chronic toxicity evaluations of Cissus sicyoides L. (Vitaceae) hydroalcoholic leaf extract.

Cissus sicyoides (Cs) has been traditionally used to treat diabetes and belongs to the family Vitaceae, and is known as "vegetable insulin". This study aimed to evaluate the acute and chronic non-clinical toxicity of hydroalcoholic extract from the leaves of Cissus sicyoides (EHA-Cs). The acute test was performed in Wistar rats, administering a single dose of 40.5 mg/kg. Behavioral parameters for pharmacological screening were observed to detect signs of Central Nervous System activity; consumption of daily food and water, and weight evaluation. After day 14, the animals were euthanized and blood samples were collected for laboratory analyses of hematological and biochemical parameters. The chronic tests were administered in doses of 4.5, 13.5 and 40.5 mg/kg. The same parameters were observed together with body temperature, glucose, exploration activity (test on the open field), and motor activity (diagnostic tests on the Rota-rod). For the group given the highest dosage during the study, histopathological examinations of vital organs were performed. For acute toxicity, there were no CNS level effects, changes in water and food consumption, or hematologic parameters. However, there was a significant decrease in weight gain for the treated females. Biochemical analyses of the treated animals presented increased levels of AST (aspartate aminotransferase) in females, uric acid levels in females and males, and amylase in males. In the chronic toxicity tests, water consumption was higher for females (at the dosages of 13.5 and 40.5 mg/kg) and for males (at 40.5 mg/kg). At the dosages of 4.5 and 13.5 mg/kg, feed consumption increased for females, while for males it decreased along with weight gain. Blood analysis presented an increase in albumin and changes in erythrocytes and hemoglobin for males (at the dose of 13.5 mg/kg). Glycemia in females (13.5 mg/kg dose) was significantly less, presenting only slight drops at the other doses. The changes were reversible in the satellite group. EHA-Cs revealed a relatively low toxicity profile (at the popular use dose), and only small changes in hematological and biochemical parameters at the dose of 13.5 mg/kg (3x the popular use dosage). In addition, EHA-Cs did not promote histological changes in vital organs such as the heart, lungs, liver and kidneys.