Mechanisms of toxicity of the inseticide imidacloprid and its metabolites desnitro-imidacloprid and imidacloprid-olefin on mitochondria and primary hepatocytes isolated from rat and HepG2 cells

• Grant number: 15/19549-8
• Support Opportunities: Regular Research Grants
• Duration: March 01, 2016 - May 31, 2018
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Fábio Erminio Mingatto
• Grantee: Fábio Erminio Mingatto
• Host Institution: Faculdade de Ciências Agrárias e Tecnológicas. Universidade Estadual Paulista (UNESP). Campus de Dracena. Dracena , SP, Brazil

Abstract

The imidacloprid is an insecticide extensively used for pest control in crops, animals and rural facilities. Recent data show that it is the third insecticide more used in Brazil and is between the most used worldwide. There are several reports in the literature of poisoning caused by the compound and the liver is one of the affected organs. The liver plays central role in metabolism, because it receives nutrients and xenobiotics that are absorbed by it, processed, stored and released into the blood and produce and store bile. The activities of biotransformation of xenobiotics are performed mainly by the liver by cytochrome P450. Most of these are associated with detoxification reactions, but they may represent a major problem because the metabolites produced may be highly reactive and more toxic than the parent compound. Mitochondria are responsible for the synthesis of almost all the ATP required for maintenance of cell structure and function. The parenchymal cells (hepatocyte) is the main functional unit of the liver and has been used extensively to study the metabolism and toxicity of a great variety of chemicals, since it provides adequate characteristics to the study of damage to these substances and their metabolites can cause. HepG2 cells are a line originated from a human hepatoblastoma and have been used as model for investigation of the effects of xenobiotics in the liver, since they have characteristics similar to cells of a normal liver, and make possible cultivation for long periods of time. Thus, we hope provide relevant information regarding the mechanism(s) of hepatotoxicity of the insecticide imidacloprid and its metabolites desnitro-imidacloprid and imidacloprid-olefin to help in the treatment in cases of intoxication by animals and humans. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BIZERRA, V, PAULO F.; GUIMARAES, ANILDA R. J. S.; MIRANDA, CAMILA A.; CONSTANTIN, RODRIGO P.; UTSUNOMIYA, KARINA S.; GILGLIONI, EDUARDO H.; CONSTANTIN, JORGETE; ISHII-IWAMOTO, EMY L.; MAIOLI, MARCOS A.; MINGATTO, FABIO E.. Enhanced cytotoxicity of imidacloprid by biotransformation in isolated hepatocytes and perfused rat liver. PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY, v. 164, p. 183-190, MAR 2020. (15/19549-8)

BIZERRA, PAULO F. V.; GUIMARAES, ANILDA R. J. S.; MAIOLI, MARCOS A.; MINGATTO, FABIO E.. Imidacloprid affects rat liver mitochondrial bioenergetics by inhibiting FoF1-ATP synthase activity. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES, v. 81, n. 8, p. 229-239, 2018. (15/19549-8)

DE JESUS SANTOS GUIMARAES, ANILDA RUFINO; VEIGA BIZERRA, PAULO FRANCISCO; MIRANDA, CAMILA ARAUJO; MINGATTO, FABIO ERMINIO. Effects of imidacloprid on viability and increase of reactive oxygen and nitrogen species in HepG2 cell line. TOXICOLOGY MECHANISMS AND METHODS, OCT 2021. (15/19549-8)