HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/6/E1492    most recent 00255.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Blaise, S. A. Articles by Daval, J.-L. Search for Related Content PubMed PubMed Citation Articles by Blaise, S. A. Articles by Daval, J.-L.

Influence of preconditioning-like hypoxia on the liver of developing methyl-deficient rats

¹INSERM U724, Vandoeuvre-lès-Nancy; ²Université Henri Poincaré, Faculté de Médecine, Vandoeuvre-lès-Nancy, France; and ³IRCCS, Oasi Maria SS, Institute for Research on Mental Retardation and Brain Aging, Troina, Italy

Submitted 24 April 2007 ; accepted in final form 27 August 2007

Deficiency in nutritional determinants of homocysteine (HCY) metabolism, such as vitamin B₁₂ and folate, during pregnancy is known to influence HCY levels in the progeny, which in turn may exert adverse effects during development, including liver defects. Since short hypoxia has been shown to induce tolerance to subsequent stress in various cells including hepatocytes, and as vitamins B deficiency and hypoxic episodes may simultaneously occur in neonates, we aimed to investigate the influence of brief postnatal hypoxia (100% N₂ for 5 min) on the liver of rat pups born from dams fed a deficient regimen, i.e., depleted in vitamins B₁₂, B₂, folate, and choline. Four experimental groups were studied: control, hypoxia, deficiency, and hypoxia + deficiency. Although hypoxia transiently stimulated HCY catabolic pathways, it was associated with a progressive increase of hyperhomocysteinemia in deficient pups, with a fall of cystathionine β-synthase activity at 21 days. At this stage, inducible NO synthase activity was dramatically increased and glutathione reductase decreased, specifically in the group combining hypoxia and deficiency. Also, hypoxia enhanced the deficiency-induced drop of the S-adenosylmethionine/S-adenosylhomocysteine ratio. In parallel, early exposure to the methyl-deficient regimen induced oxidative stress and led to hepatic steatosis, which was found to be more severe in pups additionally exposed to hypoxia. In conclusion, brief neonatal hypoxia may accentuate the long-term adverse effects of impaired HCY metabolism in the liver resulting from an inadequate nutritional regimen during pregnancy, and our data emphasize the importance of early factors on adult disease.

homocysteine; B vitamins; steatosis; oxidative stress

This article has been cited by other articles:

				S. Verbruggen, J. Sy, W. E. Gordon, J. Hsu, M. Wu, S. Chacko, D. Zurakowski, D. Burrin, and L. Castillo Ontogeny of methionine utilization and splanchnic uptake in critically ill children Am J Physiol Endocrinol Metab, November 1, 2009; 297(5): E1046 - E1055. [Abstract] [Full Text] [PDF]