Daytime Restricted Feeding Modifies the Temporal Expression of CYP1A1 and Attenuated Damage Induced by Benzo[a]pyrene in Rat Liver When Administered before CYP1A1 Acrophase

Abstract

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that heterodimerizes with the AhR nuclear translocator (ARNT) to modulate CYP1A1 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 AhR, ARNT, and CYP1A1 hepatic expression in rats are due to light/dark cycles or fasting/feeding cycles promoted by DRF. Our results show that AhR 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 ARNT expression at ZT5; meanwhile, ALF animals showed a peak of maximum expression at ZT17. An increased expression of CYP1A1 was linked to the meal time in both groups of animals. Although a high CYP1A1 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 CYP1A1 expression. These results demonstrate that DRF modifies the ARNT and CYP1A1 expression and protects from BaP toxicity.