Acute aflatoxin B1 - Induced hepatotoxicity alters gene expression and disrupts lipid and lipoprotein metabolism in rats

急性黄曲霉毒素 B1 诱发的肝毒性会改变大鼠的基因表达并破坏脂质和脂蛋白代谢

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作者:Oluwakemi Anuoluwapo Rotimi, Solomon Oladapo Rotimi, Chibueze Uchechukwu Duru, Ogheneworo Joel Ebebeinwe, Anthonia Obhio Abiodun, Boluwaji Oluwamayowa Oyeniyi, Francis Adedayo Faduyile

Abstract

In this study, alterations in lipid metabolism associated with acute aflatoxin B1 (AFB1) induced hepatotoxicity and gene expression changes underlying these effects were investigated. Rats were orally administered three doses (0.25 mg/kg, 0.5 mg/kg and 1.0 mg/kg) of AFB1 for seven days; after which blood was collected and liver excised. Lipid profiles of plasma and liver were determined spectrophotometrically while the expression of genes associated with lipid and lipoprotein metabolism was assayed by reverse transcriptase polymerase chain reaction. Acute exposure to AFB1 increased the levels of plasma and liver cholesterol, triglycerides and phospholipids. AFB1 at 0.5 mg/kg and 1.0 mg/kg resulted in a dose-dependent (1.2 and 1.5 fold, respectively) downregulation of hepatic Cpt1a with a concomitant 1.2 and 1.5 fold increase in the level of plasma FFA, respectively. A similar observation of 1.2 and 1.3 fold increase was also observed in plasma triglyceride concentration, at both respective doses. AFB1 also decreased the relative expression of Ahr, Lipc and Lcat whereas, it upregulated Scarb1 in a dose dependent manner. AFB1-induced dysregulation of the expression of lipid and lipoprotein metabolizing genes may be one mechanism linking AFB1 to altered lipid metabolism and ultimately risk for coronary heart disease.

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