Hyperglycemia-induced membrane lipid peroxidation and elevated homocysteine levels are poorly attenuated by exogenous folate in embryonic chick brains

Abstract

Injection of L-glucose (9.29 micromol/kg egg) into the air sac of fertile chicken eggs during the first 3 days of embryonic development (E(0-2)) has been reported to cause hyperglycemia and membrane lipid peroxidation in embryonic chick hepatic membranes. These observations have now been extended into embryonic chick brains at 11 days of development (theoretical stage 37). L-glucose caused a 1.7-fold increase in serum D-glucose levels (p< or =0.05), a 1.4-fold decrease in the % living embryos (p< or =0.05), a 1.1-fold decrease in embryonic masses (p< or =0.05), and a 1.4-fold decrease in embryonic brain masses (p< or =0.05) as compared to controls. L-glucose also caused a 3.8-fold increase in brain lipid hydroperoxide (LPO) levels (p< or =0.05) and complex changes in the relative fatty acid composition of brain membranes. Consistent with the hypothesis of hyperglycemia-induced increases in lipid peroxidation were decreased docosahexaenoic acid (DHA: 22: 6, n-3) levels as compared to controls (p< or =0.05). However, hyperglycemia-induced increased docosapentaenoic acid (DPA: 22:5, n-6) levels, decreased arachidonic acid (20; 4, n-6) levels, decreased linoleic acid (18:2, n-6) levels, and increased levels of several saturated short-chain membrane fatty acids were also observed as compared to controls (p< or =0.05). l-glucose caused a 12-fold increase in brain homocysteine levels, a 2.5-fold decrease in S-adenosylmethionine levels, and a 2-fold increase in S-adenosylhomocysteine levels as compared to controls (p< or =0.05). These hyperglycemia-induced alterations were poorly attenuated by exogenous folic acid (181.2 micromol/kg egg).