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.

Oscar Samuel Ávila-Rosales,Jesús Javier Espinosa-Aguirre,José Pedraza-Chaverri,Rafael Camacho-Carranza,Jorge Omar García-Rebollar,Elvia Coballase-Urrutia,Mauricio Díaz-Muñoz

doi:10.3390/toxics9060130

Oscar Samuel Ávila-Rosales, Jesús Javier Espinosa-Aguirre + Show 5 more

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https://doi.org/10.3390/toxics9060130

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Journal: Toxics	Publication Date: Jun 4, 2021
Citations: 3	License type: CC BY 4.0

Affiliation: Universidad Nacional Autónoma de México

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.

Highlights

Polycyclic aromatic hydrocarbons (PAHs) are hydrophobic compounds formed and released during incomplete combustion, volcanic eruptions, and diagenesis [1]
Under ad libitum feeding rats (ALF), Aryl hydrocarbon receptor (AhR), AhR nuclear translocator (ARNT), and CYP1A1 mRNA oscillate throughout the 24 h period, showing maximum expression at the interval ZT14 to ZT17 during the dark phase (Figure 1, Table 2)
It seems that the ARNT expression in the animals under Daytime restricted feeding (DRF) is constant throughout the 24 h period, with an expression peak at ZT5 (Figure 1B, Table 2)

Summary

Introduction

Polycyclic aromatic hydrocarbons (PAHs) are hydrophobic compounds formed and released during incomplete combustion, volcanic eruptions, and diagenesis [1]. The use of petroleum products has increased the concentration of PAHs in the environment [2], and the main sources of exposure to PAHs in humans are cigarette smoke and grilled food [3]. Benzo[a]pyrene (BaP) is considered the prototypical PAH due to its widely studied cytotoxic, mutagenic, and carcinogenic properties [4]. Aryl hydrocarbon receptor (AhR) is a receptor/transcription factor that recognizes. BaP, heterodimerizes with AhR nuclear translocator (ARNT), and regulates multiple genes, including members of the cytochrome P450 (CYP) family, such as CYP1A1 [5]. CYP1A1 metabolizes BaP into hydrophilic compounds such as 7,8-diol-BaP [6]. 7,8-diolBaP can be metabolized again by CYP1A1 to yield the highly electrophilic metabolite 7,8-

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