Evaluation of Wistar rat cardiotoxicity caused by subchronic oral exposure to the pyrethroid cypermethrin

• Grant number: 24/10785-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2024
• End date: July 31, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Diego Jose Orts y Belato
• Grantee: Gabriel Mariano de Sousa
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 21/05584-7 - Assessment of acute and chronic toxicity of the heart and brain exposed to pesticides found in potable water in Brazil, AP.JP2

Abstract

Brazil is currently one of the largest consumers of pesticides in the world. The use of these chemical compounds causes environmental contamination and problems for human health. Direct or indirect exposure to different pesticides can cause various pathologies, representing a great cost to public health. Cypermethrin is a pyrethroid class insecticide used on a large scale on agricultural and residential environments. Its mechanism of action on insects is due to the delay in the inactivation mechanism of voltage-dependent sodium channels. In cases of human exposure, although the main target is the nervous system, studies have reported that exposure to cypermethrin may be linked to cardiovascular, reproductive, hepatic and immunological toxicity through an inflammatory process and oxidative stress. In toxicity studies involving pesticides, an important parameter is the No Observed Adverse Effect Level (NOAEL). This parameter can be defined as the highest level of exposure to a pesticide without adverse effects. For cypermethrin, several studies have already been carried out with rat that were exposed acutely, subchronically and chronically. NOAEL values vary between 2 and 100 mg/kg/day depending on the type and duration of exposure, as well as the physiological system studied and animal model. The assessment of the NOAEL of a pesticide on the cardiovascular system is not mandatory for its approval for a commercial use by a regulatory agencies and, thus it is not known if the stablished NOAEL values does not cause adverse effects on the cardiovascular system. Therefore, in the present work we decide to evaluate whether cypermethrin (1 mg/kg/day) administered to Wistar rats for 28 days causes cardiotoxicity. To this end, in vivo electrocardiographic analysis as well cardiac injury markers, biochemical and morphological experiments will be performed