Oral Exposure to Atrazine Induces Oxidative Stress and Calcium Homeostasis Disruption in Spleen of Mice.

Shuying Gao,Yang Zhang,Liming Jia,Chonghua Zhang,Zhichun Wang

doi:10.1155/2016/7978219

Shuying Gao, Yang Zhang + Show 3 more

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https://doi.org/10.1155/2016/7978219

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Abstract

The widely used herbicide atrazine (ATR) can cause many adverse effects including immunotoxicity, but the underlying mechanisms are not fully understood. The current study investigated the role of oxidative stress and calcium homeostasis in ATR-induced immunotoxicity in mice. ATR at doses of 0, 100, 200, or 400 mg/kg body weight was administered to Balb/c mice daily for 21 days by oral gavage. The studies performed 24 hr after the final exposure showed that ATR could induce the generation of reactive oxygen species in the spleen of the mice, increase the level of advanced oxidation protein product (AOPP) in the host serum, and cause the depletion of reduced glutathione in the serum, each in a dose-related manner. In addition, DNA damage was observed in isolated splenocytes as evidenced by increase in DNA comet tail formation. ATR exposure also caused increases in intracellular Ca2+ within splenocytes. Moreover, ATR treatment led to increased expression of genes for some antioxidant enzymes, such as HO-1 and Gpx1, as well as increased expression of NF-κB and Ref-1 proteins in the spleen. In conclusion, it appears that oxidative stress and disruptions in calcium homeostasis might play an important role in the induction of immunotoxicity in mice by ATR.

Highlights

Atrazine (ATR, 2-chloro-4-ethylamino-6-isopropylamino-striazine), a widely used broad spectrum herbicide, belongs to chloro-s-triazine family
The current study investigated the role of oxidative stress and calcium homeostasis in ATR-induced immunotoxicity in mice
The mean fluorescence intensity of DCF in ATR treatment groups increased 1.34, 1.66, and 2.10-fold compared to the untreated group

Summary

Introduction

Atrazine (ATR, 2-chloro-4-ethylamino-6-isopropylamino-striazine), a widely used broad spectrum herbicide, belongs to chloro-s-triazine family. The primary mode of action of ATR in plants is to inhibit selectively the photosynthesis by specific binding to photosystem II, interrupting acyclic electron transport, decreasing CO2 assimilation. The chemical characteristics of ATR include lipophilicity, low water solubility, slow hydrolysis, and high solubility in organic solvents [2]. ATR and/or its metabolites, such as deethylatrazine (DEA), deisopropylatrazine (DIA), and 2-hydroxyatrazine, are frequently detected in the environment, including in samples of soil, air, and water, and have even been measured in bodily excretions [3,4,5]. ATR is considered a low toxicity herbicide, still, a number of toxicologic/epidemiologic studies have suggested that ATR could produce toxic consequences such as endocrine and reproductive alterations and behavioral and immunological dysfunction in animals and humans [7,8,9,10]

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