Role of biotransformation in the diazinon-induced toxicity in HepG2 cells and antioxidant protection by tetrahydrocurcumin

Camila Araújo Miranda; Eduardo Morais Beretta; Layra Araújo Ferreira; Emmily Sousa da Silva; Beatriz Zimermano Coimbra; Priscila Tartari Pereira; Raul Ghiraldelli Miranda; Daniel Junqueira Dorta; Flávia Thomaz Verechia Rodrigues; Fábio Erminio Mingatto

doi:10.1016/j.toxrep.2022.12.005

Role of biotransformation in the diazinon-induced toxicity in HepG2 cells and antioxidant protection by tetrahydrocurcumin

Toxicol Rep. 2022 Dec 12:10:32-39. doi: 10.1016/j.toxrep.2022.12.005. eCollection 2023.

Affiliations

¹ Department of Animal Science, College of Agricultural and Technological Sciences, São Paulo State University (Unesp), Dracena, SP, Brazil.
² Medical School, Unifadra, Faculdades de Dracena, Dracena, SP, Brazil.
³ Department of Chemistry, Faculty of Philosophy, Sciences and Letters of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.

Abstract

Diazinon (DZN) is an insecticide extensively used to control pests in crops and animals. However, its indicriminated use may lead to liver damage in animals and humans. This study aimed to evaluate the toxicity of DZN (25-150 µM) on human hepatoblastoma (HepG2) cells after 24 and 48 h of exposure and the role of its biotransformation on the toxicological potential. We also tested the protective effect of tetrahydrocurcumin (THC), an antioxidant agent, in the DZN-induced citotoxicity. DZN caused cytotoxicity in the HepG2 cells, inhibiting cell proliferation and reducing cell viability in a dose- and time-dependent manner. The pre-incubation of HepG2 cells with chemical inducers of cytochrome P450 monooxygenase 3-methylcholanthrene and phenobarbital resulted in a further decrease of cell viability associated with DZN exposure. In addition, the metabolite diazoxon was more toxic than DZN. Our results also revealed that THC alleviated DZN-induced cytotoxicity and reactive oxygen and nitrogen species (RONS) generation in HepG2 cells. In conclusion, our data provide novel insights into the involvement of biotransformation in the mechanisms of DZN-induced cytotoxicity and suggest that amelioration of RONS accumulation might be involved in the protective effect of THC on DZN-induced liver injury.

Keywords: Antioxidants; HepG2 cell line; Organophosphorus insecticides; RONS; Toxicity.