Abstract

It is well understood that liver cytochrome p450 enzymes are responsible for AFB1 bioactivation, while phase-II enzymes regulated by the transcription factor nuclear factor-erythroid-2-related factor 2 (Nrf2) are involved in detoxification of AFB1. In this study, we explored the potential of curcumin to prevent AFB1-induced liver injury by modulating liver phase-I and phase-II enzymes along with Nrf2 involved in AFB1 bioactivation and detoxification. Arbor Acres broiler were divided into four groups including control group (G1; fed only basal feed), curcumin alone-treated group (G2; 450 mg/kg feed), AFB1-fed group (G3; 5 mg/kg feed), and curcumin plus AFB1 group (G4; 5 mg AFB1+450 mg curcumin/kg feed). After 28 days, liver and blood samples were collected for different analyses. Histological and phenotypic results revealed that AFB1-induced liver injury was partially ameliorated by curcumin supplementation. Compared to AFB1 alone-treated group, serum biochemical parameters and liver antioxidant status showed that curcumin supplementation significantly prevented AFB1-induced liver injury. RT-PCR and western blot results revealed that curcumin inhibited CYP enzymes-mediated bioactivation of AFB1 at mRNA and protein level. Transcription factor Nrf2, its downstream genes such as GSTA3, and GSTM2 mRNA, and protein expression level significantly upregulated via dietary curcumin. In addition, GSTs enzyme activity was enhanced with dietary curcumin which plays a crucial role in AFB1-detoxification. Conclusively, the study provided a scientific basis for the use of curcumin in broiler’s diet and contributed to explore the multi-target preventive actions of curcumin against AFB1-induced liver injury through the modulation of phase-I and phase-II enzymes, and its potent anti-oxidative effects.

Highlights

  • Several reports demonstrated that aflatoxin B1 (AFB1) is probably the most common researched mycotoxin in the world (Liu and Wu, 2010; Abrar et al, 2013)

  • The supplementation of curcumin in the diet partially ameliorated AFB1-induced hepatic lesions (Figure 1; G4). These results confirmed the preventive effects of curcumin against AFB1-induced liver injury

  • glutathione S-transferases (GST) activity was markedly (p < 0.05) elevated in curcumin+AFB1-fed group (Figure 6B; G4) relative to AFB1fed group (Figure 6B; G3). These findings showed that curcumin actively increased GST enzyme activity to catalyze the harmful metabolites of AFB1

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Summary

Introduction

Several reports demonstrated that aflatoxin B1 (AFB1) is probably the most common researched mycotoxin in the world (Liu and Wu, 2010; Abrar et al, 2013). AFB1 causes many adverse effects such as mutagenicity, carcinogenicity, hepatotoxicity, and immunotoxicity in humans, poultry and in many other animal species (Stettler and Sengstag, 2001; Kalpana et al, 2012). AFB1 has the ability to affect more than one system at a time and cause serious alterations in the normal homeostasis of the affected organism (Ferencík and Ebringer, 2003; Herzallah, 2013). It has been placed in Group-1 human carcinogen by the International Agency for Research on Cancer (IARC) (Zuckerman, 2006). AFB1 causes liver toxicity including infiltration of mononuclear and heterophilic cells and proliferation of bile duct along with changes in liver morphology, such as increase in liver weight, enlargement, congestion, necrosis, and pallor discoloration (Newberne and Butler, 1969; Hussain and Anwar, 2008), but the susceptibility of a species to AFB1 depends on various factors such as type of breed, immunity and nutritional status, age, sex, dose, length of exposure to AFB1, and managemental conditions (Richard, 2007)

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