Copper (I)-Nicotinate Promotes Gene Expression of CYPs that Produce M1 and Q1 in Aflatoxicosed Rats

Mohammed Salah,Ahmed R Shatat,Ahmed Y Nassar,Obeid Shanab,Tahia H Saleem,Enas A Noseer,Laila Mostafa,Muammar Y Nassar

doi:10.3844/ajbbsp.2020.40.50

Abstract

Aflatoxin-contaminated food poses a serious risk to both human and animal health. Copper (1)-nicotinate (Cu+-nicotinate) complex potentiated the prophylactic effect against chronic aflatoxicosis in the experimental animals through the synthesis of less toxic metabolites M1 and Q1 which are easily excreted in urine. To investigate the action of the safety Cu+-nicotinate complex on gene expression of Cytochrome 450 (CYP450) system, the liver tissue samples of orally administered rats for 3 weeks with aflatoxin B1 (AFB1; 30 μg/kg body weight), with and without association of the copper complex (400 μg/kg body weight) were assayed for their gene expression of CYP450 families including 1A2, 3A2 and 2C11 as well as histopathological examination of the hepatic tissue samples was performed. The obtained data denoted that the Cu+-nicotinate complex significantly reduced gene expression of CYP2C11 and CYP3A2 that enhancing the most toxic epoxide metabolite. On the contrary, this complex enhanced the expression of CYP1A2 that synthesize the less toxic metabolite M1 and Q1. The histopathological examination mostly confirmed such observation as the signs of aflatoxicosis were absent in Cu+-nicotinate-treated group. Consequently, it could be predicted that the Cu+-nicotinate complex may be medically used as an inhibitory food additive agent against exposure of aflatoxicosis in the intact animals since the complex contains the copper and nicotinic acid, the two daily required biochemical elements for sustaining live in healthy conditions.

Highlights

Aflatoxins are a group of naturally occurring secondary fungal metabolites secreted mainly by Aspergillus flavus and Aspergillus parasitcus (Luttfullah and Hussain, 2011)
The acute form is characterized by severe liver damage ended by death and chronic form is manifested by reduced production, feed intake, weight gain as well as immunosuppression in animals, while in humans is manifested by Hepatocellular Carcinoma (HCC) (Balina et al, 2018)
We found that the gene expression of Cytochrome P450 (CYP450) families 3A2 and 2C11 which convert Aflatoxin B1 (AFB1) to the highly toxic metabolite was significantly increased in aflatoxicated rats (p≤0.01) while rats which treated with Cu+-nicotinate concomitant with aflatoxin showed a significant reduction in the gene expression of these two families (p≤0.01) (Fig. 3 and 4) showing no significant variance to the reference control group

Summary

Introduction

Aflatoxins are a group of naturally occurring secondary fungal metabolites secreted mainly by Aspergillus flavus and Aspergillus parasitcus (Luttfullah and Hussain, 2011). They are common contaminants of many staple foods especially maize, groundnuts and subsistence farming communities in developing countries located in tropical and sub-tropical regions (Kew, 2013; Mulenga and Siziya, 2019). The acute form is characterized by severe liver damage ended by death and chronic form is manifested by reduced production, feed intake, weight gain as well as immunosuppression in animals, while in humans is manifested by Hepatocellular Carcinoma (HCC) (Balina et al, 2018). AFB1 causes severe liver damage and has been embroiled in expanding the incidence of HCC (Rotimi et al, 2019)

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