Ávila-Rosales Oscar Samuel, Díaz-Muñoz Mauricio, Camacho-Carranza Rafael, Coballase-Urrutia Elvia, Pedraza-Chaverri José, García-Rebollar Jorge Omar, Espinosa-Aguirre Jesús Javier
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico.
Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro 76230, Mexico.
Toxics. 2021 Jun 4;9(6):130. doi: 10.3390/toxics9060130.
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that heterodimerizes with the AhR nuclear translocator (ARNT) to modulate expression, a gene involved in the biotransformation of benzo[a]pyrene (BaP). The AhR pathway shows daily variations under the control of the circadian timing system. Daytime restricted feeding (DRF) entrains the expression of genes involved in the processing of nutrients and xenobiotics to food availability. Therefore, we evaluate if temporal , and expression in rats are due to light/dark cycles or fasting/feeding cycles promoted by DRF. Our results show that oscillates throughout the 24 h period in DRF and ad libitum feeding rats (ALF), showing maximum expression at the same time points. DRF modified the peak of expression at ZT5; meanwhile, ALF animals showed a peak of maximum expression at ZT17. An increased expression of was linked to the meal time in both groups of animals. Although a high expression has been previously associated with BaP genotoxicity, our results show that, compared with the ALF group, DRF attenuated the BaP-CYP1A1 induction potency, the liver DNA-BaP adducts, the liver concentration of unmetabolized BaP, and the blood aspartate aminotransferase and alanine aminotransferase activities when BaP is administered prior to the acrophase of expression. These results demonstrate that DRF modifies the and expression and protects from BaP toxicity.
芳烃受体（AhR）是一种配体激活的转录因子，它与AhR核转运蛋白（ARNT）异二聚化以调节基因表达，该基因参与苯并[a]芘（BaP）的生物转化。AhR途径在昼夜节律系统的控制下呈现出每日变化。限时进食（DRF）使参与营养物质和外源性物质处理的基因表达与食物供应同步。因此，我们评估大鼠中基因的时间表达以及表达是否归因于DRF促进的光/暗周期或禁食/进食周期。我们的结果表明，在DRF和随意进食大鼠（ALF）中，基因在整个24小时周期内振荡，在相同时间点显示出最大表达。DRF改变了基因在ZT5时的表达峰值；与此同时，ALF动物在ZT17时显示出最大表达峰值。两组动物中基因表达的增加都与进食时间有关。尽管先前已将高基因表达与BaP遗传毒性相关联，但我们的结果表明，与ALF组相比，当在基因表达高峰期之前给予BaP时，DRF减弱了BaP-CYP1A1诱导效力、肝脏DNA-BaP加合物、未代谢BaP的肝脏浓度以及血液中天冬氨酸转氨酶和丙氨酸转氨酶的活性。这些结果表明，DRF改变了基因和基因的表达，并保护机体免受BaP毒性的影响。
