| Atrazine(ATR) is one of the most extensively used herbicide that eventually leaches into ground water and surface water from agricultural areas.Exposure to ATR do harm to the health of human and animals,especially the heart.However,the adverse of this herbicide on the heart are not fully understood.In total,the quails were divided into four groups,and each group was treated with a specific concentration of ATR(50,250 and 500mg/kg)by oral for 45 ds.Cardiac pathological alteration,inflammation response,NO metabolism,CYP450 contents and CYP450 s activities and gene expression(CYPs,nuclear receptor,regulating key factors of the coupling of ER stress and inflammation)were determined.The results showed that:1.ATR exposure caused massive inflammatory cell infiltration,cardiomyocytes arranged irregularly,myofibril loss and cracks and induced cardiac inflammatory injury.These histopathological changes suggested that ATR exposure induced inflammatory response in quail hearts.2.ATR exposure significantly caused the up-regulation of pro-inflammatory cytokines(TNF-α,IL-6,NF-κB and IL-8),down-regulation of anti-inflammatory cytokines(IL-10)expression levels and increased NO content and iNOS activity.ATR induced cardiac damage via triggering the inflammatory response and disrupting NO metabolism.These results revealed the mechanism of the ATR-induced cardiac inflammatory injury through abnormalities of inflammatory mediators and disorders of NO metabolism.3.Here,we detected CYP450 s activities and the mRNA levels of CYP450 isoforms in quail hearts.The results showed that ATR exposure could affect the CYP450 and Cyt b5 contents,CYP450s(APND,ERND,AH and NCR)activities and the expression of CYP450 isoforms(CYP1B1,CYP2C18,CYP2D6,CYP3A4,CYP3A7 and CYP4B1).ATR could regulated the expressions of nuclear receptors such as CAR,AHR and PXR to induce the expression of CYPs subtype genes.4.The present study provides new insights regarding the mechanism of the ATR-induced cardiotoxicity through up-regulating the expression levels of GRP78 and XBP-1s,triggering ER stress,activating the gene expression of IRE1α/TRAF2/NF-κB signaling pathway related factors(IRE1α,TRAF2,IKK and NF-κB)and inducing inflammatory response in quail hearts.In conclusion,ATR exposure could induce cardiac inflammatory injury via activating nuclear xenobiotic receptors responses,disrupting cytochrome P450 homeostasis and CYP450 isoforms transcription,altering NO metabolism and triggering ER stress and inflammatory response by activating IRE1α/TRAF2/NF-κB signaling pathway. |
