title: Thiol compounds metabolism in mice, rats and humans: comparative study and potential explanation of rodents protection against vascular diseases.
abstract: 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.
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Service de Biochimie, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Likogianni
authors.forename: Nathalie
authors.initials: N
authors.lastname: Janel
authors.forename: Aurélie
authors.initials: A
authors.lastname: Ledru
authors.forename: Philippe
authors.initials: P
authors.lastname: Beaune
authors.forename: Jean Louis
authors.initials: JL
authors.lastname: Paul
authors.forename: Karine
authors.initials: K
authors.lastname: Demuth
mesh_terms: 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
chemical_list: D013438:Sulfhydryl Compounds; D014803:Vitamin B Complex