Curcumin Prevents Aflatoxin B₁ Hepatoxicity by Inhibition of Cytochrome P450 Isozymes in Chick Liver

Toxins (Basel). 2016 Nov 10;8(11):327. doi: 10.3390/toxins8110327.

Abstract

This study was designed to establish if Curcumin (CM) alleviates Aflatoxin B₁ (AFB₁)-induced hepatotoxic effects and to determine whether alteration of the expression of cytochrome P450 (CYP450) isozymes is involved in the regulation of these effects in chick liver. One-day-old male broilers (n = 120) were divided into four groups and used in a two by two factorial trial in which the main factors included supplementing AFB₁ (< 5 vs. 100 μg/kg) and CM (0 vs. 150 mg/kg) in a corn/soybean-based diet. Administration of AFB₁ induced liver injury, significantly decreasing albumin and total protein concentrations and increasing alanine aminotransferase and aspartate aminotransferase activities in serum, and induced hepatic histological lesions at week 2. AFB₁ also significantly decreased hepatic glutathione peroxidase, catalase, and glutathione levels, while increasing malondialdehyde, 8-hydroxydeoxyguanosine, and exo-AFB₁-8,9-epoxide (AFBO)-DNA concentrations. In addition, the mRNA and/or activity of enzymes responsible for the bioactivation of AFB₁ into AFBO-including CYP1A1, CYP1A2, CYP2A6, and CYP3A4-were significantly induced in liver microsomes after 2-week exposure to AFB₁. These alterations induced by AFB₁ were prevented by CM supplementation. Conclusively, dietary CM protected chicks from AFB₁-induced liver injury, potentially through the synergistic actions of increased antioxidant capacities and inhibition of the pivotal CYP450 isozyme-mediated activation of AFB₁ to toxic AFBO.

Keywords: AFBO–DNA; CYP450; aflatoxin B1; chicks; curcumin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aflatoxin B1 / toxicity*
  • Animals
  • Carcinogens / toxicity
  • Chemical and Drug Induced Liver Injury / drug therapy
  • Chemical and Drug Induced Liver Injury / metabolism*
  • Chemical and Drug Induced Liver Injury / pathology
  • Chickens
  • Curcumin / pharmacology*
  • Curcumin / therapeutic use
  • Cytochrome P-450 Enzyme Inhibitors / pharmacology*
  • Cytochrome P-450 Enzyme Inhibitors / therapeutic use
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • DNA Adducts
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / metabolism
  • RNA, Messenger / metabolism

Substances

  • Carcinogens
  • Cytochrome P-450 Enzyme Inhibitors
  • DNA Adducts
  • Isoenzymes
  • RNA, Messenger
  • Cytochrome P-450 Enzyme System
  • Aflatoxin B1
  • Curcumin