title: 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 asHO-1andGpx1, 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.
authors.affiliation: Department of Toxicological Science, School of Public Health, Harbin Medical University, Harbin, Heilongjiang Province 150081, China.
authors.forename: Shuying
authors.identifier: 0000-0003-2616-767X
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Toxicological Science, School of Public Health, Harbin Medical University, Harbin, Heilongjiang Province 150081, China.
authors.forename: Zhichun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Harbin Center for Disease Control and Prevention, Harbin, Heilongjiang Province 150056, China.
authors.forename: Chonghua
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Environmental Monitoring Centre of Heilongjiang Province, Harbin, Heilongjiang Province 150056, China.
authors.forename: Liming
authors.initials: L
authors.lastname: Jia
authors.affiliation: Department of Toxicological Science, School of Public Health, Harbin Medical University, Harbin, Heilongjiang Province 150081, China.
authors.forename: Yang
authors.identifier: 0000-0002-1887-6786
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D062107:Advanced Oxidation Protein Products / Q000097:blood; D000818:Animals; D001280:Atrazine / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism*; D004249:DNA Damage; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects*; D042541:Intracellular Space / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000473:pathology*
chemical_list: D062107:Advanced Oxidation Protein Products; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase; D051547:Heme Oxygenase-1; C486216:Apex1 protein, mouse; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D005978:Glutathione; D001280:Atrazine; D002118:Calcium