Periodate-oxidized adenosine inhibits the formation of dimethylselenide and trimethylselenonium ion in mice treated with selenite.
The metabolic detoxification of selenite and many other selenium compounds involves a series of S-adenosylmethionine-dependent methylations yielding dimethylselenide (DMSe), which is exhaled, and trimethylselenonium ion (TMSe), which is excreted in the urine. This paper shows that periodate-oxidized adenosine (Adox) inhibits these methylation reactions in vivo and increases the toxicity of selenite. When Adox was injected in mice at 100 mumol/kg 30 min before injection of [75Se]selenite at 0.4 mg Se/kg the appearances of [75Se]DMSe in the breath and [75Se]TMSe in the liver were completely inhibited for 90 min. This was mediated by accumulation of S-adenosylhomocysteine, the methyltransferase inhibitor, in the livers of Adox-treated mice due to inhibition of its hydrolase enzyme. During 24 h, Adox-treated mice excreted no detectable urinary [75Se]TMSe and exhaled only 20% as much [75Se]DMSe as controls. The urine of Adox-treated mice also contained S-adenosylhomocysteine at a level (ca. 4 mM), 200 times that of untreated mice, which provided a convenient index of methylation potential in the intact animal. When three groups of three mice each were injected with 100 mumol Adox/kg, selenite at 4 mg Se/kg, or a combination of the two, the mice receiving the combination were dead within 2 days, while the mice in the other two groups all survived at least 4 days. These results verify the enzymatic nature of selenium methylation in vivo, support its importance in detoxification, and indicate the value of Adox in further studies of selenium metabolism.
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D008658:Inactivation, Metabolic; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008745:Methylation; D051379:Mice; D009942:Organometallic Compounds / Q000378:metabolism* / Q000652:urine; D016566:Organoselenium Compounds; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism; D020887:Selenious Acid; D012643:Selenium / Q000378:metabolism* / Q000633:toxicity / Q000652:urine; D018036:Selenium Compounds
D009942:Organometallic Compounds; D016566:Organoselenium Compounds; D018036:Selenium Compounds; C027579:periodate-oxidized adenosine; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D020887:Selenious Acid; D012643:Selenium; D000241:Adenosine; C003717:trimethylselenonium; C013503:dimethylselenide