The effect of (L)-cysteine and (L)-2-oxothiazolidine-4-carboxylic acid (OTZ) on urinary oxalate excretion: studies using a hyperoxaluric rat model.
OBJECTIVE
To determine the efficacy of (L)-cysteine and (L)-2-oxothiazolidine-4-carboxylic acid (OTZ) in reducing urinary oxalate excretion under hyperoxaluric conditions and to determine whether by inclusion of glycolate in a standard diet, cysteine:glyoxylate adduct can be detected in hyperoxaluric rats given either compound.


METHODS
Hyperoxaluria (200% above basal) was induced 2 days prior to commencement of the studies and maintained throughout. After a 3 days baseline, animals were randomly allocated to a control or treatment group. Standard diet containing either (L)-cysteine or OTZ was then fed to the treatment groups for 5 days while standard diet alone was fed to the control groups. Urinary oxalate excretion was subsequently monitored and average daily rates were then compared with basal values. Plasma and urine were analyzed for adduct.


RESULTS
Both (L)-cysteine and OTZ significantly reduced urinary oxalate excretion relative to the basal hyperoxaluric level (28.6 +/- 1.5 micromol./day). While (L)-cysteine reduced oxalate excretion over the 5 day treatment period by only 7.82 +/- 1.39 micromol./day (27%), OTZ reduced it by 12.34 +/- 1.58 micromol./day (43%). Adduct could not be detected in plasma or urine in this study.


CONCLUSIONS
This study confirms that both (L)-cysteine and OTZ are effective in reducing urinary oxalate excretion under hyperoxaluric conditions, with OTZ being more effective than (L)-cysteine. These compounds were shown to be 3- to 4-fold more effective in reducing urinary oxalate excretion under hyperoxaluric conditions when compared with the results from previous studies under normooxaluric conditions.
Baker
P W
PW
Division of Clinical Biochemistry, Institute of Medical and Veterinary Science, Adelaide, Australia.
Rofe
A M
AM
Bais
R
R
D000818:Animals; D003545:Cysteine / Q000494:pharmacology*; D004195:Disease Models, Animal; D008297:Male; D010070:Oxalates / Q000652:urine*; D011761:Pyrrolidonecarboxylic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines; D014545:Urinary Calculi / Q000378:metabolism
D010070:Oxalates; D013844:Thiazoles; D053778:Thiazolidines; D003545:Cysteine; D011761:Pyrrolidonecarboxylic Acid; C029536:2-oxothiazolidine-4-carboxylic acid