Thiol compounds metabolism in mice, rats and humans: comparative study and potential explanation of rodents protection against vascular diseases.
BACKGROUND
Rodents are often used as animal models to dissect mechanisms underlying hyperhomocysteinemia atherogenicity in humans. However, neither wild-type rodents nor cystathionine beta-synthase deficient mice develop spontaneous atherosclerosis. We investigated whether species-specific differences in thiols metabolism may explain the respective sensitivity of rodents and humans to hyperhomocysteinemia.


METHODS
Thiols and vitamins B levels were determined in normohomocysteinemic humans and rodents, and in hyperhomocysteinemic mice.


RESULTS
In basal status, although plasma homocysteine, cysteine and cysteinylglycine levels were lower, glutathione levels were higher in mice than in humans (4.0+/-1.6 vs. 7.9+/-2.2, P<0.0005; 147.4+/-40.3 vs. 278.5+/-50.0, P<0.0001; 2.3+/-0.7 vs. 36.6+/-7.3, P<0.0001; and 70.9+/-20.1 vs. 4.6+/-1.6, P<0.0001). Serum vitamin B12 and folate levels were 2.5- and 7.7-fold higher in rats than in humans. In wild-type mice, the increase in plasma Hcy levels induced by methionine-enriched diet was accompanied by a proportional increase in GSH levels.


CONCLUSIONS
GSH levels are enough to modulate Hcy effects in normo- and hyperhomocysteinemic mice but not in humans. This rodents characteristic, likely supported by species differences in the relative contribution of remethylation and transsulfuration pathways, may partly explain their protection against atherosclerosis.
Likogianni
Vasiliki
V
Assistance Publique-Hôpitaux de Paris, Service de Biochimie, Hôpital Européen Georges Pompidou, Paris, France.
Janel
Nathalie
N
Ledru
Aurélie
A
Beaune
Philippe
P
Paul
Jean Louis
JL
Demuth
Karine
K
D000818:Animals; D006801:Humans; D051379:Mice; D051381:Rats; D013045:Species Specificity; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D014652:Vascular Diseases / Q000517:prevention & control*; D014803:Vitamin B Complex / Q000097:blood
D013438:Sulfhydryl Compounds; D014803:Vitamin B Complex