The organotellurium compound ammonium trichloro(dioxoethylene-o,o')tellurate reacts with homocysteine to form homocystine and decreases homocysteine levels in hyperhomocysteinemic mice.
Ammonium trichloro(dioxoethylene-o,o')tellurate (AS101) is an organotellurium compound with pleiotropic functions that has been associated with antitumoral, immunomodulatory and antineurodegenerative activities. Tellurium compounds with a +4 oxidation state, such as AS101, react uniquely with thiols, forming disulfide molecules. In light of this, we tested whether AS101 can react with the amino acid homocysteine both in vitro and in vivo. AS101 conferred protection against homocysteine-induced apoptosis of HL-60 cells. The protective mechanism of AS101 against homocysteine toxicity was directly mediated by its chemical reactivity, whereby AS101 reacted with homocysteine to form homocystine, the less toxic disulfide form of homocysteine. Moreover, AS101 was shown here to reduce the levels of total homocysteine in an in vivo model of hyperhomocysteinemia. As a result, AS101 also prevented sperm cells from undergoing homocysteine-induced DNA fragmentation. Taken together, our results suggest that the organotellurium compound AS101 may be of clinical value in reducing total circulatory homocysteine levels.
Okun
Eitan
E
CAIR Institute, The Safdié AIDS and Immunology Research Center, Bar-Ilan University, Ramat-Gan, Israel.
Dikshtein
Yahav
Y
Carmely
Alon
A
Saida
Hagar
H
Frei
Gabi
G
Sela
Ben-Ami
BA
Varshavsky
Lydia
L
Ofir
Asher
A
Levy
Esthy
E
Albeck
Michael
M
Sredni
Benjamin
B
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D005030:Ethylenes / Q000494:pharmacology* / Q000627:therapeutic use; D018922:HL-60 Cells; D006710:Homocysteine / Q000378:metabolism*; D006711:Homocystine / Q000378:metabolism*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013094:Spermatozoa / Q000473:pathology
D005030:Ethylenes; D006710:Homocysteine; D006711:Homocystine; C054105:ammonium trichloro(dioxoethylene-O,O'-)tellurate