title: High-dose sodium selenite toxicity cannot be prevented by the co-administration of pharmacological levels of epigallocatechin-3-gallate which in turn aggravates the toxicity.
abstract: Selenium, an essential trace element, can also be toxic at higher levels of exposure. Several lines of evidence show epigallocatechin-3-gallate (EGCG), a predominant component of green tea catechins with numerous health benefits, can ameliorate the toxicity of many agents. A proof-in-principle experiment was conducted to determine if EGCG would ameliorate sodium selenite-induced growth suppression. Mice were intraperitioneally injected with selenite once daily for five days at a dose of 3 mg Se/kg, which fully suppressed animal growth but did not cause death. Surprisingly the co-administration of the selenite and nontoxic doses of EGCG (10, 20 and 40 mg/kg, intraperitioneally) resulted in the mortality of treated mice in a dose and time-dependent manner (33.3%, 100% and 100%, respectively). EGCG-selenite induced lethality did not result from enhanced selenium accumulation but appeared to involve the suppression of a selenite-induced adaptive response as evidenced by hepatic glutathione S-transferase activity. While EGCG has been reported to ameliorate the toxicity of some agents, the induction of mortality by combined treatment with pharmacological doses of selenium and EGCG is a previously unrecognized synergism that must be considered not only in the remediation of high environmental selenium exposures but also in the development of pharmaceuticals and nutriceuticals.
authors.affiliation: Key Laboratory of Tea Biochemistry & Biotechnology, School of Tea and Food Science, Anhui Agricultural University, Hefei 230036, Anhui, PR China.
authors.forename: Kang
authors.initials: K
authors.lastname: Sun
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wu
authors.forename: Yijun
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Wan
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Thompson
authors.forename: Jinsong
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions / Q000401:mortality; D005982:Glutathione Transferase / Q000378:metabolism; D006130:Growth Disorders / Q000139:chemically induced; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology; D012643:Selenium / Q000493:pharmacokinetics; D018038:Sodium Selenite / Q000008:administration & dosage / Q000633:toxicity*; D014018:Tissue Distribution
chemical_list: D020011:Protective Agents; D002392:Catechin; C045651:epigallocatechin gallate; D005982:Glutathione Transferase; D012643:Selenium; D018038:Sodium Selenite