Role Of Nuclear Receptor Responses On Atrazine Induced Mitochondrial Dysfunction In Quail Cerebrum

Atrazine(ATR)has become one of the most commonly used broad-spectrum herbicides worldwide.Due to its chemical stability and long residual persistence,ATR can frequently be detected in rivers and soil,leading to potential ecological hazard.ATR caused extensive toxicity in humans and animals via oxidative stress.However,the neurotoxicity of ATR remains unclear.To evaluate the mechanism of the ATR-induced cerebrum toxicity,male quails were treated by with 0,50,250 and 500 mg/kg ATR for 45 days.Histologic and morphometric features in cerebrum were observed,and the expression of nuclear xenobiotic receptor and CYP450 s,oxidative stress,mitochondrial function and mitophagy related genes were detected.The results indicated that:1.ATR can induce the histopathological and ultrastructural changes in quail cerebrum,the results showed ATR can cause cerebrum damage.2.250 mg/kg and 500 mg/kg ATR can interfere the expression of mitochondrial function related genes,increase the levels of mitophagy related genes(Pink1,Parkin).The results indicated ATR could cause mitochondrial dysfunction and mitophagy.3.ATR can increase H2O2 and MDA content and inhibit the activities of T-AOC,T-SOD,GST,CAT,reduce the content of T-AOC,these results showed oxidative stress is one of the mechanisms of ATR induced mitochondrial damage.4.ATR can activate NXRs(AHR,CAR and PXR)response and increased the CYP450 s genes expression.Nevertheless,ATR would interfere CYP450 s homeostasis(increase CYP450 and Cyt b5 content and the activities of AH and NCR;decrease the activities of ERND and APND).The results showed that AHR\CAR\PXR mediated NXRs responses and CYP450 s homeostasis regulation is one of the important mechanisms on ATR induced neurotoxicity in quails.