Bisphenol A enhances cadmium toxicity through estrogen receptor.
To clarify the action of estrogenic endocrine disruptors on cadmium (Cd)-induced metallothionein (MT) synthesis in the liver, we investigated the effects of bisphenol A (BPA) on hepatic MT-I mRNA expression and MT contents after Cd injection. Liver damage after Cd injection was assessed by measuring glutamic-pyruvic transaminase (GPT) and glutamic-oxaloacetic transaminase (GOT) activities in the serum. It was found that BPA reduced the Cd-induced expression of MT-I mRNA and MT protein in the liver. The administration of tamoxifen, an estrogen receptor antagonist, prevented the reduction of hepatic MT content by PA. Moreover both the GPT and GOT activities of the BPA-treated groups were higher than those of the control groups. These findings suggest that BPA reduced hepatic MT synthesis after Cd injection via the estrogen receptor which resulted in increased damage to the liver.
Sogawa
N
N
Department of Dental Pharmacology, Okayama University Graduate School of Medicine and Dentistry, Japan. sogawa@md.okayama-u.ac.jp
Onodera
K
K
Sogawa
C A
CA
Mukubo
Y
Y
Fukuoka
H
H
Oda
N
N
Furuta
H
H
D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood / Q000187:drug effects; D001559:Benzhydryl Compounds; D019256:Cadmium Chloride / Q000819:agonists / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004965:Estrogen Antagonists / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage; D005786:Gene Expression Regulation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D010636:Phenols / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000187:drug effects*; D013629:Tamoxifen / Q000494:pharmacology; D000098826:Bisphenol A Compounds
D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D001559:Benzhydryl Compounds; D019256:Cadmium Chloride; D004965:Estrogen Antagonists; D000431:Ethanol; D008668:Metallothionein; D010636:Phenols; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013629:Tamoxifen; C006780:bisphenol A; D000098826:Bisphenol A Compounds