کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2597180 1562405 2008 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on heme oxygenase-1, biliverdin IXα reductase and δ-aminolevulinic acid synthetase 1 in rats with wild-type or variant AH receptor
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on heme oxygenase-1, biliverdin IXα reductase and δ-aminolevulinic acid synthetase 1 in rats with wild-type or variant AH receptor
چکیده انگلیسی

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes hepatic accumulation of biliverdin and its monoglucuronide in moderately TCDD-resistant line B rats, but not in highly TCDD-resistant line A rats. In the mammalian heme degradation process, heme is cleaved to biliverdin by the rate-limiting enzyme heme oxygenase-1 (HO-1). Subsequently, biliverdin IXα reductase (BVRA) catalyzes the reduction of biliverdin to bilirubin. In heme biosynthesis, the rate-limiting enzyme is δ-aminolevulinic acid synthetase 1 (ALAS1). The effect of TCDD on HO-1, BVRA and ALAS1 was studied at the levels of mRNA (all three enzymes), protein expression (HO-1), and enzymatic activity (BVRA, liver only) in order to determine whether the accumulation of biliverdin could be due to their altered expression. In both lines A and B, 300 μg/kg TCDD transiently repressed hepatic HO-1 mRNA on day 2 but induced HO-1 protein expression at later time-points; however, the impact emerged earlier (day 14 vs. day 35) in line B rats. In spleen, TCDD repressed HO-1 mRNA and protein expression in lines A and B through days 2–35, but did not affect its mRNA levels in TCDD-sensitive L-E rats (10 days after 100 μg/kg). In all rat strains/lines, there was a strong repression of ALAS1 and a moderate induction of BVRA mRNA in liver, but mostly not in spleen. Hepatic BVRA activity was increased in lines A and B on day 14. At 5 weeks, it was still elevated in line A but reduced to 51% of control in line B. The results suggest that hepatic heme degradation is induced by TCDD in rats; however, this does not alone explain the accumulation of biliverdin in line B rats. Other factors such as the late repression of BVRA found here and possibly oxidative stress may be important contributors to biliverdin accumulation in these rats.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 250, Issues 2–3, 4 September 2008, Pages 132–142
نویسندگان
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