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

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.

Oxidative stress in triazine pesticide toxicity: a review of the main biomarker findings

“…The latter two were also low in the kidney tissue (66). Similar effects were noticed in mice receiving 100, 200, or 400 mg kg -1 bw of atrazine by gavage every day for 21 days (67).…”

<p>Downregulation of miR-200a Protects Mouse Leydig Cells Against Triptolide by Triggering Autophagy</p>

“… 21 Excessive amounts of ROS can result in lasting oxidative stress and can induce cell apoptosis. 22 , 23 In addition, oxidative stress could affect normal spermatozoa production by impairing the steroidogenic capacity of the testis. 22 As we know, MDA is used as an important biomarker for examining oxidative stress, while SOD and GSH are important antioxidants.…”

Exposure to Atrazine Induces Lung Inflammation through Nrf2-HO1 andBeclin 1/LC3 Pathways

“…Additionally, the mice were weighted and observed for any clinical symptoms, and the information was recorded by the animal care staff. Seven days after the aerosol exposure, the mice were sacrificed and lung tissue, bronchoalveolar lavage fluid (BALF), and blood samples were collected for histology and biochemical analysis, as previously described [40,42,43,[47][48][49]. The ATR dosage was chosen based on other previous studies, but for the first time, ATR was not administered by oral gavage but instead by aerosol, because there is still limited knowledge of the effects of ATR on the lungs [50][51][52].…”

“…However, until today, few reports have explored the molecular mechanisms underlying ATR induction of lung problems. Some of the most accredited hypothesis that could explain the mechanism of toxicity induced by ATR is the production of reactive oxygen species (ROS) [22,[39][40][41][42][43]. In particular, some of the study results that prompted us to investigate the ways by which ATR exerts its lung toxicity were the discovery by Zhao and colleagues that ATR could induce a response activated by nuclear factor erythroid 2-related factors 2 (Nrf2); the increase in the malondialdehyde levels as well as in the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) found by Batti et al; and finally the results by Song et al that demonstrated that ATR enhanced the apoptotic and autophagic processes [22,39,44].…”