A "chemical" concept for the therapy of glyoxylate-induced oxalurias (1).
Glyoxylic acid is the toxic principle of acquired and inherited oxalurias. A "chemical", not enzyme-mediated detoxication concept for the trapping of this aldehyde is described, based on a spontaneous formation of alkaloid-type heterocycles by reaction with biogenic amines or amino acids. 5,5-Dimethylthiazolidine-2(R,S)-4(S)-dicarboxylic acid, prepared by the condensation of D(-)-penicillamine with glyoxylic acid, was found to be formed quickly in vitro, to be stable in vivo and of good physiological compatibility. Renal elimination of the unchanged thiazolidine occurs mainly within 24 h, after administration of its calcium salt to NMRI-mice. Recovery up to 85% of the applied dose was quantitatively monitored by HPLC after derivatization to the corresponding fluorescent dansyl compound, which was unequivocally identified by MS analysis after isolation from mice urine.
Bringmann
G
G
Institute of Organic Chemistry, University of Würzburg, Am Hubland, Germany.
Feineis
D
D
Hesselmann
C
C
Schneider
S
S
Koob
M
M
Henschler
D
D
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003619:Dansyl Compounds / Q000737:chemistry; D005260:Female; D006038:Glyoxylates / Q000633:toxicity*; D006863:Hydrogen-Ion Concentration; D006959:Hyperoxaluria / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism; D013058:Mass Spectrometry; D051379:Mice; D010396:Penicillamine / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013237:Stereoisomerism; D013844:Thiazoles / Q000378:metabolism
D003619:Dansyl Compounds; D006038:Glyoxylates; D013844:Thiazoles; C074389:5,5-dimethylthiazolidine-2,4-dicarboxylic acid; D010396:Penicillamine; C031150:glyoxylic acid