Hepatic, renal, and pancreatic damage associated with chronic exposure to oral and inhaled 2,4-dichlorophenoxy acetic ac

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ORIGINAL ARTICLE

Hepatic, renal, and pancreatic damage associated with chronic exposure to oral and inhaled 2,4-dichlorophenoxy acetic acid (2,4-d): an environmental exposure model in rats Daniel José Pimentel Bonfim 1 & Letícia Rocha Magalhães 2 & Pedro Henrique Nahas Chagas 2 Fernanda de Maria Serra 3 & Liliane Aparecida Tanus Benatti 4 & Gisele Alborghetti Nai 5,6

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Received: 7 January 2020 / Accepted: 1 August 2020 / Published online: 12 August 2020 # Springer-Verlag London Ltd., part of Springer Nature 2020

Abstract 2,4-Diclophenoxyacetic acid (2,4-D) is one of the most widely used herbicides in the world. The aim of this study was to evaluate the possible toxic effect of chronic exposure to oral and inhaled 2,4-D herbicide on the liver, kidney, and pancreas by simulating environmental exposure. Eighty male albino adult Wistar rats divided into eight groups were exposed for 6 months to inhaled and oral (contaminated feed) three different doses of 2,4-D [3.71 × 10−3 g of active ingredient per hectare (g a.i./ha), 6.19 × 10−3 g a.i./ ha and 9.28 × 10−3 g a.i./ha]. Blood, liver, kidney, spleen, and pancreas samples were collected for analysis. There was a difference in ALT (alanine aminotransferase) levels between groups exposed to 2,4-D. The groups exposed to oral 2,4-D had a higher incidence of steatosis, and exposed to high doses had increased liver inflammation. All animals in the groups exposed to high 2,4-D concentrations showed renal tubular hydropic degeneration. Atrophy of Langerhans islets was observed in animals exposed to 2,4-D. The simulation of chronic environmental exposure to the 2,4-D herbicide resulted in hepatic changes that were both dose-dependent and exposure-dependent and renal and pancreatic changes that were dose-dependent. Keywords Agrochemical . Occupational exposure . Dietary exposure . Pre-diabetic status . Animal models

Introduction 2,4-Diclophenoxyacetic acid (2,4-D) is one of the most widely used herbicides in the world due to its wide application in many types of crops, forests and lawns, and its low cost (Liu et al. 2013). Humans may be exposed to products that contain 2,4-D, both occupationally and

* Gisele Alborghetti Nai [email protected] Daniel José Pimentel Bonfim [email protected]

nonoccupationally, by inhalation, dermal absorption or ingestion, by direct contact, or with wastes found in water, air, soil, and food (International Agency for Research on Cancer (IARC) 2015). 2,4-D may be present in water due to its direct use in water or for agricultural or forest applications (International Agency for Research on Cancer (IARC) 2015). This can lead to the

1

Graduate Program in Animal Science, Universidade do Oeste Paulista (UNOESTE), Presidente Prudente, SP 19050-680, Brazil

2

Medical College, Universidade do Oeste Paulista (UNOESTE), Presidente Prudente, SP 19050-680, Brazil

3

Faculty of Biomedicine, Universidade do Oeste Paulista (UNOESTE), Presidente Prudente, SP 19050-680, Brazil

4

Universidade do Oeste Paulista (UNOESTE), Presidente Prudente, SP 190