title: High-dose thiamine therapy counters dyslipidemia and advanced glycation of plasma protein in streptozotocin-induced diabetic rats.
abstract: 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.
authors.affiliation: Department of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, Essex CO4 3SQ, UK.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Karachalias
authors.forename: Roya
authors.initials: R
authors.lastname: Babaei-Jadidi
authors.forename: Christian
authors.initials: C
authors.lastname: Kupich
authors.forename: Naila
authors.initials: N
authors.lastname: Ahmed
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Thornalley
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism*; D048909:Diabetes Complications / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D017127:Glycation End Products, Advanced / Q000097:blood*; D006031:Glycosylation; D006949:Hyperlipidemias / Q000517:prevention & control*; D051381:Rats; D013831:Thiamine / Q000031:analogs & derivatives / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D001798:Blood Proteins; D017127:Glycation End Products, Advanced; D013831:Thiamine; C013835:benphothiamine