Adedara I A, Owumi S E, Uwaifo A O, Farombi E O
Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Nigeria.
Toxicol Ind Health. 2010 Nov;26(10):717-24. doi: 10.1177/0748233710377772. Epub 2010 Sep 13.
The present study investigated the effects of aflatoxin B₁ (AFB₁) and ethanol co-exposure on biomarkers of hepatic damage in mice. Four groups of adult male mice were treated for 7 consecutive days. Control mice received corn oil alone at a dose of 2 mL/kg bw. One group was treated with ethanol at a dose of 500 µL/kg bw and another group administered 9 mg/kg bw of AFB₁ dissolved in corn oil. The fourth group was co-administered with ethanol and AFB₁. The body and liver weights of treated mice decreased significantly when compared with corresponding control. Alone, ethanol and AFB(1) treatment separately increased serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT) and alkaline phosphatase (ALP). Alcohol dehydrogenase (ALD) activity was markedly elevated in ethanol-treated mice but was unaffected by AFB₁ treatment. Co-exposure of AFB₁ and ethanol escalated the activities of these serum enzymes. Administration of ethanol and AFB₁ separately resulted in significant decrease in both non-enzymatic antioxidant glutathione (GSH) level and enzymatic antioxidant catalase (CAT) and glutathione-S-transferase (GST) activities, whereas lipid peroxidation was markedly elevated. Superoxide dismutase activity and vitamin C level remained unaffected in all treatment groups. Co-exposure of animals to ethanol and AFB₁ showed additive effects on the activities of GST and CAT as well as on the GSH level. Histopathological study revealed that these compounds interact together to exacerbate their individual effects on the liver. In summary, the data presented showed that AFB₁ and ethanol co-exposure induced severe oxidative damage to the liver of mice and as such humans consuming excessive amount of ethanol and diets contaminated with AFB₁ simultaneously may be at greater risk of the hepatotoxic effects of these compounds.
本研究调查了黄曲霉毒素B₁（AFB₁）与乙醇共同暴露对小鼠肝脏损伤生物标志物的影响。将四组成年雄性小鼠连续处理7天。对照小鼠单独接受剂量为2 mL/kg体重的玉米油。一组用剂量为500 µL/kg体重的乙醇处理，另一组给予溶解于玉米油中的9 mg/kg体重的AFB₁。第四组同时给予乙醇和AFB₁。与相应对照组相比，处理后小鼠的体重和肝脏重量显著下降。单独使用乙醇和AFB₁处理分别增加了天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、γ-谷氨酰转移酶（GGT）和碱性磷酸酶（ALP）的血清活性。乙醇处理的小鼠中酒精脱氢酶（ALD）活性显著升高，但不受AFB₁处理的影响。AFB₁与乙醇共同暴露使这些血清酶的活性升高。单独给予乙醇和AFB₁导致非酶抗氧化剂谷胱甘肽（GSH）水平以及酶抗氧化剂过氧化氢酶（CAT）和谷胱甘肽-S-转移酶（GST）活性均显著降低，而脂质过氧化显著升高。所有处理组中超氧化物歧化酶活性和维生素C水平均未受影响。动物同时暴露于乙醇和AFB₁对GST和CAT的活性以及GSH水平显示出相加作用。组织病理学研究表明，这些化合物相互作用会加剧它们对肝脏的个体影响。总之，所呈现的数据表明，AFB₁与乙醇共同暴露会对小鼠肝脏造成严重的氧化损伤，因此，同时摄入过量乙醇和受AFB₁污染饮食 的人类可能面临这些化合物肝毒性作用的更大风险。
