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

摘要: Abstract 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 highly A rats. In the mammalian heme degradation process, is cleaved to by rate-limiting enzyme oxygenase-1 (HO-1). Subsequently, IXα reductase (BVRA) catalyzes reduction bilirubin. biosynthesis, δ-aminolevulinic acid synthetase 1 (ALAS1). The effect TCDD on HO-1, BVRA ALAS1 was studied at levels mRNA (all three enzymes), protein expression (HO-1), enzymatic activity (BVRA, liver only) order determine whether could be due their altered expression. both lines B, 300 μg/kg transiently repressed HO-1 day 2 induced later time-points; however, impact emerged earlier (day 14 vs. 35) spleen, through days 2–35, did affect TCDD-sensitive L-E rats (10 after 100 μg/kg). all rat strains/lines, there a strong repression moderate induction liver, mostly spleen. Hepatic increased 14. At 5 weeks, it still elevated reduced 51% control B. results suggest that rats; this does alone explain Other factors such as late found here possibly oxidative stress may important contributors these