Pharmacokinetics of 2-Oxothiazolidine-4-Carboxylate, a Cysteine Prodrug, and Cysteine

1998 ◽  
Vol 38 (10) ◽  
pp. 945-950 ◽  
Author(s):  
Peter R. Gwilt ◽  
Lorraine E. Radick ◽  
Xiao-Yan Li ◽  
John J. Whalen ◽  
Cynthia D. Leaf
Keyword(s):  
Cysteine Prodrug

scholarly journals Elevation of whole-blood glutathione in peritoneal dialysis patients by L-2-oxothiazolidine-4-carboxylate, a cysteine prodrug (Procysteine).

1998 ◽  
Vol 9 (6) ◽  
pp. 1093-1099 ◽  
Author(s):  
J B Moberly ◽  
J Logan ◽  
P R Borum ◽  
K O Story ◽  
L E Webb ◽  
...  
Keyword(s):  
Renal Failure ◽  
Peritoneal Dialysis ◽  
Whole Blood ◽  
Oxidant Stress ◽  
Cellular Damage ◽  
Controlled Study ◽  
Dialysis Patients ◽  
Protein Thiols ◽  
Cysteine Prodrug

Glutathione is a major cellular antioxidant that protects protein thiols and inhibits cellular damage due to oxygen free radicals. It has been reported previously that patients undergoing dialysis have low levels of blood glutathione, which may lead to increased susceptibility to oxidant stress. L-2-oxothiazolidine-4-carboxylic acid (OTZ) is a cysteine prodrug that raises cellular glutathione levels by increasing delivery of cysteine, the rate-limiting substrate for glutathione synthesis. This study investigates the effect of OTZ on blood glutathione in a blinded, placebo-controlled study of patients with chronic renal failure treated by peritoneal dialysis. Twenty patients were randomly selected to receive OTZ (0.5 g three times a day orally with meals) or placebo for 14 d. Patients visited the clinic for predose blood collection and safety evaluation at baseline (days 3, 7, and 14 and again at 14 d from the last dose [follow-up]). Glutathione concentrations were determined in whole blood by HPLC. OTZ resulted in a significant rise in whole-blood glutathione at days 7 (594 +/- 129 mumol/L) and 14 (620 +/- 108 mumol/L) compared with baseline (544 +/- 139 mumol/L) (P < 0.01 and P < 0.05, respectively). Glutathione was also significantly increased at days 7 and 14 when normalized by hematocrit (Hct) or hemoglobin to correct for anemic status (e.g., 20.7 +/- 5.7 mumol/L per % Hct [day 7] and 20.9 +/- 4.0 mumol/L per % Hct [day 14] versus 18.0 +/- 4.2 mumol/L per % Hct [baseline]; P < 0.05). Glutathione levels did not change in the placebo group at any patient visit, and levels in the OTZ-treated group returned to baseline at follow-up. There were no serious adverse events attributable to OTZ, and the drug appeared to be well tolerated by patients with renal failure treated by continuous ambulatory peritoneal dialysis. Our results show that OTZ increases blood glutathione levels, which may improve antioxidant status in dialysis patients.

scholarly journals Biological Activities and Potential Oral Applications of N-Acetylcysteine: Progress and Prospects

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Yanping Pei ◽  
Huan Liu ◽  
Yi Yang ◽  
Yanwei Yang ◽  
Yang Jiao ◽  
...  
Keyword(s):  
Health Care ◽  
Biological Activities ◽  
Antimicrobial Property ◽  
Treatment Modalities ◽  
Oral Medicine ◽  
Pharmacological Activities ◽  
Therapeutic Activities ◽  
Cysteine Prodrug ◽  
Mucolytic Agent ◽  
Biological And Pharmacological Activities

N-Acetylcysteine (NAC), a cysteine prodrug and glutathione (GSH) precursor, has been used for several decades in clinical therapeutic practices as a mucolytic agent and for the treatment of disorders associated with GSH deficiency. Other therapeutic activities of NAC include inhibition of inflammation/NF-κB signaling and expression of proinflammatory cytokines. N-Acetylcysteine is also a nonantibiotic compound possessing antimicrobial property and exerts anticarcinogenic and antimutagenic effects against certain types of cancer. Recently, studies describing potentially important biological and pharmacological activities of NAC have stimulated interests in using NAC-based therapeutics for oral health care. The present review focused on the biological activities of NAC and its potential oral applications. The potential side effects of NAC and formulations for drug delivery were also discussed, with the intent of advancing NAC-associated treatment modalities in oral medicine.

Influence of a cysteine prodrug, L-2-oxothiazolidine-4-carboxylic acid, on the urinary elimination of mercapturic acids of ethylene oxide, dibromoethane, and acrylonitrile: a dose–effect study

1989 ◽  
Vol 67 (3) ◽  
pp. 207-212 ◽  
Author(s):  
R. Goyal ◽  
R. Tardif ◽  
J. Brodeur
Keyword(s):  
Carboxylic Acid ◽  
Ethylene Oxide ◽  
Urinary Metabolites ◽  
Effect Study ◽  
Dose Effect ◽  
Mercapturic Acids ◽  
Glutathione Pathway ◽  
The Relationship ◽  
Higher Doses ◽  
Cysteine Prodrug

Metabolic disposition of ethylene oxide, dibromoethane, and acrylonitrile in rats after acute exposure was studied by examining the relationship between dose and urinary metabolites, and by establishing the influence of a glutathione precursor, L-2-oxothiazolidine-4-carboxylic acid (OTCA), on the above relationship. Respective urinary metabolites, hydroxyethylmercapturic acid, cyanoethylmercapturic acid, thiocyanate, and ethylene glycol, were quantified to estimate the extent to which each compound was metabolized. The animals were given either ethylene oxide (0.34, 0.68, or 1.36 mmol/kg), dibromoethane (0.2, 0.4, or 0.6 mmol/kg), or acrylonitrile (0.10, 0.38, or 0.76 mmol/kg). Urine samples were collected at 24 h. The metabolic biotransformation of all three chemicals to their respective mercapturic acids was strongly indicative of saturable metabolism. Administration of OTCA (4–5 mmol/kg) enhanced gluthathione availability and increased excretion of urinary mercapturic acids at the higher doses of the chemicals. This study indicates that OTCA increases the capacity for detoxification via the glutathione pathway thereby partially correcting the nonlinearity between the administered dose of ethylene oxide, dibromoethane, and acrylonitrile and the amount of certain urinary metabolites.Key words: ethylene oxide metabolism, dibromoethane metabolism, acrylonitrile metabolism, mercapturic acids, glutathione, cysteine prodrugs, L-2-oxothiazolidine-4-carboxylic acid.

L-Cysteine prodrug protects against cyclophosphamide urotoxicity without compromising therapeutic activity

1991 ◽  
Vol 28 (3) ◽  
pp. 166-170 ◽  
Author(s):  
Jeanette C. Roberts ◽  
David J. Francetic ◽  
Richard T. Zera
Keyword(s):  
Therapeutic Activity ◽  
Cysteine Prodrug
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