Atrazine induced oxidative stress and mitochondrial dysfunction in quail (Coturnix C. coturnix) kidney via modulating Nrf2 signaling pathway

• Published in: Chemosphere (Oxford) 2018-12, Vol.212, p.974-982
• Main Authors: Zhang, Cong, Qin, Lei, Dou, Da-Chang, Li, Xue-Nan, Ge, Jing, Li, Jin-Long
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Atrazine; Atrazine - toxicity; Coturnix - metabolism; Dose-Response Relationship, Drug; Herbicides - toxicity; Kidney - cytology; Kidney - drug effects; Kidney - metabolism; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondrial dysfunction; Nephrotoxicity; NF-E2-Related Factor 2 - metabolism; Nrf2 signaling pathway; Oxidative stress; Oxidative Stress - drug effects; Quail; Signal Transduction - drug effects
• ISSN: 0045-6535; 1879-1298
• DOI: 10.1016/j.chemosphere.2018.08.138

Atrazine (ATR) is a most used herbicide which is believed as a pivotal determinant of environmental nephrosis, but potential mechanism is still largely unclear. This study intends to reveal a novel mechanism of ATR-induced nephrotoxicity. Quail were treated with 0, 50, 250 and 500 mg ATR/kg/d by oral gavage for 45 days. Kidney coefficient was decreased, biochemical and morphologic indices reflecting the kidney injury were significantly increased in ATR-exposed quail. ATR exposure upregulated the expression of proapoptotic factors (Bax, Caspase 3 and FasL) and downregulated antiapoptotic factor (Bcl-2). Notably, cristae of mitochondria decreased, mitochondrial malformation and mitochondrial vacuolar degeneration were observed in ATR-exposed quail. ATR induced the disorder of mitochondrial function related factors expressions and promoted oxidative damage. Furthermore, ATR induced toxicities in the expression of Nrf2 and Nrf2-target genes. In conclusion, ATR altered the microstructure and function of quail kidney. ATR induced renal damage via causing mitochondrial dysfunction, influencing mitochondrial function related genes expression, modulating Nrf2 signaling pathway. This study suggested ATR induced the nephrotoxicity via disturbing the transcription of mitochondrial function related factors and Nrf2 signaling pathway. Graphical abstract illustrating the proposed mechanism by ATR-induced nephrotoxicity in quail. Nrf2 signaling pathway was blocked by ATR in kidney of quail. Mitochondria in quail kidney were the target organelles of ATR induced nephrotoxicity. ATR damaged mitochondrial function and morphology. It is deduced that ATR-induced nephrotoxicity is associated with mitochondrial dysfunction and interruption of Nrf2 signaling pathway. [Display omitted] •ATR decreased kidney coefficient, impaired histology and function of kidney.•ATR disturbed mitochondrial structure and function related genes expression.•ATR exposure stimulated apoptosis and oxidative stress.•ATR induced variation of Nrf2 signaling pathway and antioxidant response.