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Inhibition of human and rat CYP1A1 enzyme by grapefruit juice compounds

Rebeca Santes-Palacios1, Antonio Romo-Mancillas2, Rafael Camacho-Carranza1

  • 1Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Cd. de México, México.

Toxicology Letters
|July 23, 2016
PubMed

Insights

Grapefruit compounds naringenin and 6

Area of Science:

  • Biochemistry
  • Pharmacology
  • Toxicology

Background:

  • Cytochrome P4501A1 (CYP1A1) metabolizes polycyclic aromatic hydrocarbons, influencing carcinogenesis.
  • Human and rat CYP1A1 exhibit significant amino acid sequence differences, impacting interspecies extrapolation of research findings.

Purpose of the Study:

  • To investigate the inhibitory effects of naringenin and 6',7'-dihydroxybergamottin from grapefruit juice on human and rat CYP1A1 activity.
  • To elucidate the mechanisms of inhibition and explore potential differences between human and rat CYP1A1.

Main Methods:

  • Enzyme kinetics studies to determine inhibition types and constants.
  • Computational simulations, including molecular docking, to visualize inhibitor binding to the CYP1A1 active site.

Main Results:

  • Naringenin and 6',7'-dihydroxybergamottin were identified as competitive inhibitors of both human and rat CYP1A1.
  • Naringenin demonstrated a mixed-type inhibition on rat CYP1A1.
  • Computational docking suggested that these compounds may inhibit 7-ethoxyresorufin oxidation by binding to the CYP1A1 active site.

Conclusions:

  • Naringenin and 6',7'-dihydroxybergamottin inhibit human and rat CYP1A1 through competitive mechanisms.
  • Species-specific differences exist in the inhibitory mechanisms of these grapefruit compounds on CYP1A1.
  • These findings highlight the importance of considering interspecies variations when assessing drug-metabolizing enzyme inhibition.
Keywords:
CYP1A1 inhibitorDihydroxybergamottinMolecular modelingNaringenin

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