Evaluation of Toxicity and Oxidative Stress of 2-Acetylpyridine- N (4)-orthochlorophenyl Thiosemicarbazone.
Andressa Brito LiraGabrieli Lessa ParrilhaGabriela Tafaela DiasFernanda Samara de Sousa SaraivaGabriel Corrêa VeríssimoRayane Siqueira de SousaTania Maria Sarmento SilvaAbrahão Alves de Oliveira FilhoAdriano Francisco AlvesElaine Maria de Souza-FagundesHeloisa BeraldoMaria Aparecida GomesMargareth de Fatima Formiga Melo DinizPublished in: Oxidative medicine and cellular longevity (2022)
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.
Keyphrases
- oxidative stress
- induced apoptosis
- weight gain
- nitric oxide
- diabetic rats
- ischemia reperfusion injury
- dna damage
- body mass index
- oxide nanoparticles
- molecular docking
- liver failure
- blood pressure
- birth weight
- blood brain barrier
- weight loss
- clinical trial
- endoplasmic reticulum stress
- hydrogen peroxide
- bipolar disorder
- fatty acid
- signaling pathway
- stress induced
- heat shock
- acute respiratory distress syndrome
- gestational age