Citotoxicity of the inseticide Diazinon in HepG2 cells: mitochondrial activity and role of biotransformation

• Grant number: 19/12497-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): August 01, 2019
• Effective date (End): November 30, 2021
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Fábio Erminio Mingatto
• Grantee: Camila Araújo Miranda
• Host Institution: Faculdade de Ciências Agrárias e Tecnológicas. Universidade Estadual Paulista (UNESP). Campus de Dracena. Dracena , SP, Brazil

Abstract

Organophosphate pesticides were developed in the 1940s and completely replaced the compounds of the group of organochlorines, which were already resistant to insects. Diazinon is an organophosphate insecticide widely used in agriculture for pest control, veterinary medicine as antiparasitic, mainly in production animals, and in the control of domestic pests. It is applied as a systemic insecticide that kills insects via ingestion or contact, interfering with the control of the nervous system by inhibiting cholinesterase enzymes, causing an accumulation of acetylcholine in the nerve synapses, triggering a greater stimulation of the cholinergic synapses in the Central Nervous System (CNS), parasympathetic nerves and glands. Diazinon does not present a toxic effect only in the CNS, but also in the reproductive, respiratory and cardiovascular systems, thus presenting high toxicity for pets, cattle and humans that, when intoxicated, can die. There are also several reports in the literature of intoxication caused by the substance in the liver. For the accomplishment of the present study, the cell line derived from human hepatocarcinoma HepG2 was selected, being a model widely used in the scientific literature in studies of hepatic toxicity and the metabolism of xenobiotics, since these cells maintain many of the specialized functions of human normal hepatocytes. Thus, it is expected to provide relevant information on the mechanisms of hepatotoxicity of diazinon, for help in the treatment in case of intoxication by animals and humans.