Hacettepe University, Faculty of Pharmacy, Department of Toxicology, Ankara 06100, Turkey.
J Trace Elem Med Biol. 2012 Jan;26(1):36-41. doi: 10.1016/j.jtemb.2011.12.002. Epub 2012 Feb 25.
The objective of this study was to investigate the effects of iodine (I(2)) and/or selenium (Se) deficiency on thyroid hormones and hepatic xenobiotic metabolizing enzyme systems using a triple animal model. Three-week-old male Wistar rats were fed for seven weeks. Se deficiency was introduced by a diet containing <0.005 mg/kg Se, and I(2) deficiency was produced by sodium perchlorate containing drinking water. The levels of plasma thyroid hormones [total T(4) (TT(4)), total T(3) (TT(3))], thyroid stimulating hormone (TSH); total microsomal cytochrome P450 (CYP450) and cytochrome b5 (CYP b5) levels; activities of microsomal NADPH-cytochrome P450 reductase (P450R), microsomal aniline hydroxylase (CYP2E1), microsomal 7-ethoxyresorufin O-deethylase (EROD), microsomal 7-pentoxyresorufin O-depentylase (PROD) and cytosolic glutathione S-transferase (GST) were determined. In I(2) deficiency total CYP450 levels, activities of CYP2E1, EROD and GST decreased, and CYP b5 content increased significantly. In Se-deficient rats, total CYP450 level and CYP2E1 activity increased, and EROD and GST activities and CYP b5 level decreased significantly. In combined I(2) and Se deficiency, except for CYP450 content and CYP2E1 activity, all enzyme activities and CYP b5 content decreased significantly compared to control group. Overall results of this study have suggested that metabolism of xenobiotics as well as endogenous compounds is affected by Se and I(2) status.
本研究旨在采用三重动物模型研究碘(I(2))和/或硒(Se)缺乏对甲状腺激素和肝外源性化合物代谢酶系统的影响。3 周龄雄性 Wistar 大鼠喂养 7 周。通过含硒量<0.005mg/kg 的饮食引入 Se 缺乏,通过含高氯酸钠的饮用水产生 I(2)缺乏。测定血浆甲状腺激素[总 T(4)(TT(4)),总 T(3)(TT(3))]、促甲状腺激素(TSH);总微粒体细胞色素 P450(CYP450)和细胞色素 b5(CYP b5)水平;微粒体 NADPH-细胞色素 P450 还原酶(P450R)、微粒体苯胺羟化酶(CYP2E1)、微粒体 7-乙氧基荧蒽 O-脱乙基酶(EROD)、微粒体 7-戊氧基荧蒽 O-脱戊基酶(PROD)和胞质谷胱甘肽 S-转移酶(GST)的活性。在 I(2)缺乏时,总 CYP450 水平、CYP2E1、EROD 和 GST 活性降低,CYP b5 含量显著增加。在 Se 缺乏的大鼠中,总 CYP450 水平和 CYP2E1 活性增加,而 EROD 和 GST 活性以及 CYP b5 水平显著降低。在 I(2)和 Se 联合缺乏时,除了 CYP450 含量和 CYP2E1 活性外,所有酶活性和 CYP b5 含量与对照组相比均显著降低。本研究的总体结果表明,外源性化合物和内源性化合物的代谢受 Se 和 I(2)状态的影响。