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High‐Dose Thiamine Therapy Counters Dyslipidemia and Advanced Glycation of Plasma Protein in Streptozotocin‐Induced Diabetic Rats
Author(s) -
KARACHALIAS NIKOLAOS,
BABAEIJADIDI ROYA,
KUPICH CHRISTIAN,
AHMED NAILA,
THORNALLEY PAUL J.
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1333.090
Subject(s) - thiamine , methylglyoxal , glycation , chemistry , endocrinology , streptozotocin , medicine , diabetes mellitus , dyslipidemia , glyoxal , pyridoxamine , pharmacology , vitamin , biochemistry , vitamin b6 , enzyme , organic chemistry
A bstract : The streptozotocin‐induced (STZ) diabetic rat experimental model of diabetes on insulin maintenance therapy exhibits dyslipidemia, mild thiamine deficiency, and increased plasma protein advanced glycation end products (AGEs). The reversal of thiamine deficiency by high‐dose thiamine and S‐benzoylthiamine monophosphate (benfotiamine) prevented the development of incipient nephropathy. Recently, we reported that high‐dose thiamine (but not benfotiamine) countered diabetic dyslipidemia. To understand further the differences between the effects of thiamine and benfotiamine therapy, we quantified the levels of the AGEs in plasma protein. We found hydroimidazolone AGE residues derived from glyoxal and methylglyoxal, G‐H1 and MG‐H1, were increased 115% and 68% in STZ diabetic rats, with respect to normal controls, and were normalized by both thiamine and benfotiamine; whereas N‐carboxymethyl‐lysine (CML) and N‐carboxyethyl‐lysine (CEL) residues were increased 74% and 118% in STZ diabetic rats and were normalized by thiamine only. The lack of effect of benfotiamine on plasma CML and CEL residue concentrations suggests there may be important precursors of plasma protein CML and CEL residues other than glyoxal and methylglyoxal. These are probably lipid‐derived aldehydes.