title: Effects of Ziram on Rat and Human 11β-Hydroxysteroid Dehydrogenase Isoforms.
abstract: Ziram is a widely used fungicide for crops. Its endocrine disrupting action is largely unknown. 11β-Hydroxysteroid dehydrogenases, isoforms 1 (HSD11B1) and 2 (HSD11B2), have been demonstrated to be the regulators of the local levels of active glucocorticoids, which have broad physiological actions. In the present study, the potency of ziram was tested for its inhibition of rat and human HSD11B1 and HSD11B2. Ziram showed the inhibition of rat HSD11B1 reductase with IC50 of 87.07 μM but no inhibition of human enzyme at 100 μM. Ziram showed the inhibition of both rat and human HSD11B2 with IC50 of 90.26 and 34.93 μM, respectively. Ziram exerted competitive inhibition of rat HSD11B1 when 11-dehydrocorticosterone was used and mixed inhibition when NADPH was supplied. Ziram exerted a noncompetitive inhibition of both rat and human HSD11B2 when steroid substrates were used and an uncompetitive inhibition when NAD(+) was supplied. Increased DTT concentrations antagonized rat and human HSD11B2 activities, suggesting that the cysteine residues are associated with the inhibition of ziram. In conclusion, for humans, ziram is a selective inhibitor of HSD11B2, implying that this agent may cause excessive glucocorticoid action in local tissues such as the kidney, brain, and placenta.
authors: Center of Scientific Research, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University , Wenzhou, Zhejiang 325027, China.
authors: Xiaoheng
authors: X
authors: Li
authors: Department of Anesthesiology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University , Wenzhou, Zhejiang 325027, China.
authors: Baiping
authors: B
authors: Mao
authors: Center of Scientific Research, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University , Wenzhou, Zhejiang 325027, China.
authors: Yaoyao
authors: Y
authors: Dong
authors: Department of Pediatric Pulmonology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University , Wenzhou, Zhejiang 325027, China.
authors: Yuan
authors: Y
authors: Li
authors: Department of Pediatric Pulmonology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University , Wenzhou, Zhejiang 325027, China.
authors: Meizheng
authors: M
authors: Zhan
authors: Center of Scientific Research, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University , Wenzhou, Zhejiang 325027, China.
authors: Yanfang
authors: Y
authors: Bai
authors: Department of Anesthesiology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University , Wenzhou, Zhejiang 325027, China.
authors: Qingquan
authors: Q
authors: Lian
authors: Department of Anesthesiology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University , Wenzhou, Zhejiang 325027, China.
authors: Ren-Shan
authors: RS
authors: Ge
authors: Department of Pediatric Pulmonology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University , Wenzhou, Zhejiang 325027, China.
authors: Leping
authors: L
authors: Ye
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D015039:Ziram / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D007527:Isoenzymes; D015039:Ziram; D042842:11-beta-Hydroxysteroid Dehydrogenases