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

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.

Identification of the Anti-Aflatoxinogenic Activity of Micromeria graeca and Elucidation of Its Molecular Mechanism in Aspergillus flavus

“…Recent studies have pointed out the use of physio-chemical approaches to counteract aflatoxin contamination [8,9] while others were based on the detoxification properties or the protective physiological effect of bacterial metabolites or natural extracts used as feed supplements [10,11,12,13]. Although proven to be efficient, these approaches remain strictly restricted to animal feed.…”

Protective effects of curcumin against aflatoxicosis: A comprehensive review

“…Upon administration of AFB1, the mRNA level as well as enzymes activity involved in bioactivation of AFB1 into AFBO (e.g., CYP1A1, CYP1A2, CYP2A6, CYP3A4) were on the considerable rise at week 2. Further analyses highlighted the inhibitory effect of curcumin on such changes (Zhang et al, ). By adopting a completely different animal model, Nile tilapia Oreochromis niloticus , Mahfouz () designed a dietary dose of AFB1 (200 ppb) over 16 weeks in combination with and without curcumin (5 mg/kg diet).…”

“…There have been some studies indicating that AFB1‐elevated CYPs were significantly mitigated by dietary curcumin (Figure , route B) (Diaz, Murcia, & Cepeda, ; Guengerich et al, ). Indeed, CYP1A1, CYP1A2, CYP2A6, and CYP3A4 are considerably elevated in response to AFB1 consumption (Zhang et al, ). CYP2A6 and CYP1A1 are shown to be implicated in the bioactivation of AFB1 into AFBO in the chicken liver while CYP1A2 as well as CYP3A4 are those of high priority in bioactivating AFB1 into AFBO in mammals (Diaz et al, ; Guengerich et al, ).…”

“…Therefore, restriction in activity of these enzymes could decrease formation of AFBO. The AFBO–DNA, known as a main toxic adduct of AFBO (Guengerich et al, ; Yunus, Razzazi‐Fazeli et al, ), was in sharp decline in response to the dietary supplementation of curcumin, suggesting that such inhibitory actions of curcumin is more likely to be mediated via inhibition of CYPs (e.g., CYP1A1, CYP1A2, CYP3A4, CYP2A6 activity), which, in turn, could manifest as decreased formation of AFBO (Firozi, Aboobaker, & Bhattacharya, ; Nayak & Sashidhar, ; Zhang et al, ). The CYPs refer to paramount metabolizing enzymes, most of which are chiefly expressed in the liver.…”

“…From clinical perspective, drug metabolism is contingent on CYPs, the presence of which potentiates the effective clearance of xenobiotics from the body (Anzenbacher & Anzenbacherová, ; Zanger & Schwab, ). However, CYPs are able to bioactivate biologically inert carcinogens as well as toxins, for instance 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (Smith, Stoner, & Yang, ), N‐nitrosonornicotine (Patten et al, ), hexamethylphosphoramide (Su et al, ), benzo(a)pyrene (Garg, Gupta, & Maru, ), AFB1 (Yunus, Razzazi‐Fazeli et al, ), and 2,6‐dichlorobenzonitrile (Xie, D'Agostino, Zhou, & Ding, ) to electrophilic metabolites potent for development of toxicity, cell death, and at times cellular transformation that ends up cancer (Zhang et al, ). Considering that curcumin can strongly inhibit CYPs by stabilizing the membrane, it could function as a potentially antimutagen and anticarcinogen agent for a number of carcinogens as well as toxins in chemopreventive trials.…”