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Oxidative Medicine and Cellular... 2016Iron and copper release participates in the myocardial injury under ischemic conditions and hence protection might be achieved by iron chelators. Data on copper...
Iron and copper release participates in the myocardial injury under ischemic conditions and hence protection might be achieved by iron chelators. Data on copper chelation are, however, sparse. The effect of the clinically used copper chelator D-penicillamine in the catecholamine model of acute myocardial injury was tested in cardiomyoblast cell line H9c2 and in Wistar Han rats. D-Penicillamine had a protective effect against catecholamine-induced injury both in vitro and in vivo. It protected H9c2 cells against the catecholamine-induced viability loss in a dose-dependent manner. In animals, both intravenous D-penicillamine doses of 11 (low) and 44 mg/kg (high) decreased the mortality caused by s.c. isoprenaline (100 mg/kg) from 36% to 14% and 22%, respectively. However, whereas the low D-penicillamine dose decreased the release of cardiac troponin T (specific marker of myocardial injury), the high dose resulted in an increase. Interestingly, the high dose led to a marked elevation in plasma vitamin C. This might be related to potentiation of oxidative stress, as suggested by additional in vitro experiments with D-penicillamine (iron reduction and the Fenton reaction). In conclusion, D-penicillamine has protective potential against catecholamine-induced cardiotoxicity; however the optimal dose selection seems to be crucial for further application.
Topics: Animals; Cardiotonic Agents; Catecholamines; Cell Line; Cell Survival; Deferoxamine; Hydrogen-Ion Concentration; Ions; Iron; Iron Chelating Agents; Male; Myocardium; Penicillamine; Rats, Wistar; Troponin T
PubMed: 26788248
DOI: 10.1155/2016/5213532 -
Inorganic Chemistry Jul 2009The complex formation between cadmium(II) and the ligands cysteine (H(2)Cys) and penicillamine (H(2)Pen = 3,3'-dimethylcysteine) in aqueous solutions, having C(Cd(II))...
The complex formation between cadmium(II) and the ligands cysteine (H(2)Cys) and penicillamine (H(2)Pen = 3,3'-dimethylcysteine) in aqueous solutions, having C(Cd(II)) approximately 0.1 mol dm(-3) and C(H(2)L) = 0.2-2 mol dm(-3), was studied at pH = 7.5 and 11.0 by means of (113)Cd NMR and Cd K- and L(3)-edge X-ray absorption spectroscopy. For all cadmium(II)-cysteine molar ratios, the mean Cd-S and Cd-(N/O) bond distances were found in the ranges 2.52-2.54 and 2.27-2.35 A, respectively. The corresponding cadmium(II)-penicillamine complexes showed slightly shorter Cd-S bonds, 2.50-2.53 A, but with the Cd-(N/O) bond distances in a similar wide range, 2.28-2.33 A. For the molar ratio C(H(2)L)/C(Cd(II)) = 2, the (113)Cd chemical shifts, in the range 509-527 ppm at both pH values, indicated complexes with distorted tetrahedral CdS(2)N(N/O) coordination geometry. With a large excess of cysteine (molar ratios C(H(2)Cys)/C(Cd(II)) >or= 10), complexes with CdS(4) coordination geometry dominate, consistent with the (113)Cd NMR chemical shifts, delta approximately 680 ppm at pH 7.5 and 636-658 ppm at pH 11.0, and their mean Cd-S distances were 2.53 +/- 0.02 A. At pH 7.5, the complexes are almost exclusively sulfur-coordinated as [Cd(S-cysteinate)(4)](n-), while at higher pH, the deprotonation of the amine groups promotes chelate formation. At pH 11.0, a minor amount of the [Cd(Cys)(3)](4-) complex with CdS(3)N coordination is formed. For the corresponding penicillamine solutions with molar ratios C(H(2)Pen)/C(Cd(II)) >or= 10, the (113)Cd NMR chemical shifts, delta approximately 600 ppm at pH 7.5 and 578 ppm at pH 11.0, together with the average bond distances, Cd-S 2.53 +/- 0.02 A and Cd-(N/O) 2.30-2.33 A, indicate that [Cd(penicillaminate)(3)](n-) complexes with chelating CdS(3)(N/O) coordination dominate already at pH 7.5 and become mixed with CdS(2)N(N/O) complexes at pH 11.0. The present study reveals differences between cysteine and penicillamine as ligands to the cadmium(II) ion that can explain why cysteine-rich metallothionines are capable of capturing cadmium(II) ions, while penicillamine, clinically useful for treating the toxic effects of mercury(II) and lead(II) exposure, is not efficient against cadmium(II) poisoning.
Topics: Cadmium; Cysteine; Magnetic Resonance Spectroscopy; Penicillamine; Spectrum Analysis; X-Rays
PubMed: 19469490
DOI: 10.1021/ic802278r -
The Cochrane Database of Systematic... Sep 2013The rate of retinopathy of prematurity (ROP) in moderately premature infants has decreased dramatically with improved care in the neonatal intensive care unit. A low... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The rate of retinopathy of prematurity (ROP) in moderately premature infants has decreased dramatically with improved care in the neonatal intensive care unit. A low rate of this disorder was unexpectedly observed among infants treated with intravenous D-penicillamine to prevent hyperbilirubinaemia. This observation led to the investigation of its use, both enterally as well as intravenously, to prevent ROP.
OBJECTIVES
To determine the effect of prophylactic administration of D-penicillamine on the incidence of acute ROP or severe ROP and other morbidities in preterm infants.
SEARCH METHODS
We used the Cochrane Neonatal Review Group search strategy. Two review authors independently searched multiple electronic databases, previous reviews including cross references, abstracts, conference/symposia proceedings, and expert informants. We updated the search on November 27, 2012.
SELECTION CRITERIA
We included randomised or quasi-randomised controlled trials if they administered D-penicillamine and compared it with no treatment or placebo to premature infants and reported on the outcome of ROP.
DATA COLLECTION AND ANALYSIS
We used the criteria and standard methods of the Cochrane Neonatal Review Group to assess the methodological quality of the included trials. One review author examined trials for validity. A second review author checked validity and they reached consensus on the final data before entry into this review. We used the standards of the Neonatal Cochrane Review Group to analyse data.
MAIN RESULTS
Three randomised trials met the inclusion criteria. The meta-analysis showed no significant differences in the risk of any stage ROP (typical risk ratio (RR) 0.32, 95% confidence interval (CI) 0.03 to 3.70), severe ROP (typical RR 0.38, 95% CI 0.03 to 4.26) or death (typical RR 0.95, 95% CI 0.68 to 1.32) in all treated infants. When the subgroup of infants under 1500 g birth weight was examined, the results were similar. No side effects were reported, and follow-up at one year revealed no significant differences in spasticity or developmental delay.
AUTHORS' CONCLUSIONS
Administration of prophylactic D-penicillamine in preterm infants does not prevent acute or severe ROP, death or neurodevelopmental delay. D-penicillamine cannot be recommended for the prevention of ROP based on the available evidence.
Topics: Chelating Agents; Humans; Infant, Newborn; Infant, Premature; Penicillamine; Randomized Controlled Trials as Topic; Retinopathy of Prematurity
PubMed: 24002688
DOI: 10.1002/14651858.CD001073.pub2 -
The Cochrane Database of Systematic... Jan 2006Primary sclerosing cholangitis is a cholestatic disease. D-penicillamine is suggested as a treatment option due to its copper reducing and immunomodulatory potential. (Review)
Review
BACKGROUND
Primary sclerosing cholangitis is a cholestatic disease. D-penicillamine is suggested as a treatment option due to its copper reducing and immunomodulatory potential.
OBJECTIVES
To evaluate the beneficial and harmful effects of D-penicillamine for patients with primary sclerosing cholangitis.
SEARCH STRATEGY
Eligible trials were identified through searches of The Cochrane Hepato-Biliary Group Controlled Trials Register (August 2005), The Cochrane Central Register of Controlled Trials in The Cochrane Library (Issue 3, 2005), MEDLINE (1950 to August 2005), EMBASE (1980 to August 2005), Science Citation Index EXPANDED (1945 to August 2005), and reference lists of relevant articles. Authors of trials and pharmaceutical companies known to produce D-penicillamine were also contacted.
SELECTION CRITERIA
Randomised clinical trials comparing D-penicillamine in any dose, duration, and route of administration versus placebo, no intervention, or other intervention(s). Trials were included irrespective of publication status, year of publication, language, or blinding.
DATA COLLECTION AND ANALYSIS
Both authors selected the trials, extracted data, and evaluated the methodological quality of the trials with respect to the generation of allocation sequence, allocation concealment, blinding, and follow-up. The results were reported by intention-to-treat analysis. The outcomes were presented as relative risk (RR) or weighted mean difference (WMD), both with 95% confidence intervals (CI).
MAIN RESULTS
One randomised trial was identified and included in the review. It was of low methodological quality. The trial compared D-penicillamine versus placebo in 70 patients with primary sclerosing cholangitis. Compared with placebo, D-penicillamine therapy had no significant effect on mortality (RR 1.14, 95% CI 0.49 to 2.64), liver transplantation (RR 1.11, 95% CI 0.39 to 3.17), hepatic histologic progression (RR 1.17, 95% CI 0.79 to 1.74), or cholangiographic deterioration (RR 0.87, 95% CI 0.43 to 1.79). D-penicillamine led to a significant improvement in the serum aspartate aminotransferase (WMD -23.00 U/L; 95% CI -30.66 to -15.34), but not in serum bilirubin level (WMD 0.40 mg/L; 95% CI -0.19 to 0.99) and serum alkaline phosphatases activity (WMD 44.00 U/L; 95% CI -37.89 to 125.89). There were significantly more adverse events in patients receiving D-penicillamine (P = 0.013).
AUTHORS' CONCLUSIONS
There is not sufficient evidence to support or refute the use of D-penicillamine for patients with primary sclerosing cholangitis. We do not recommend the use of D-penicillamine for patients with primary sclerosing cholangitis outside randomised trials.
Topics: Cholangitis, Sclerosing; Humans; Penicillamine; Randomized Controlled Trials as Topic
PubMed: 16437475
DOI: 10.1002/14651858.CD004182.pub3 -
British Journal of Clinical Pharmacology Oct 19901. The plasma pharmacokinetics of D-penicillamine (D-pen) and D-penicillamine-albumin disulphide (D-pen-alb) were examined over a dosage interval in six patients with...
1. The plasma pharmacokinetics of D-penicillamine (D-pen) and D-penicillamine-albumin disulphide (D-pen-alb) were examined over a dosage interval in six patients with rheumatoid arthritis. In two of these, 24 h synovial fluid profiles of D-pen and D-pen-alb were also obtained. 2. D-pen was undetectable in plasma at the beginning of the study. The peak concentration (5.4 +/- 1.2 microM) occurred at between 45 min and 2 h and the mean elimination half-life was 0.6 h. D-pen-alb, however, was present at a mean plasma concentration of 19.1 microM prior to dosage, peaked at 26.2 microM and was eliminated with a half-life of 40 h. 3. D-pen concentrations in synovial fluid rose more slowly and peaked lower than in plasma. D-pen-alb was present in synovial fluid of the patients at 50.1% and 83.6%, respectively, of the simultaneous plasma concentration prior to dosage. Concentrations varied during the study interval, corresponding to changes in plasma concentrations. 4. These results demonstrate that D-pen forms stable conjugates with protein in treated patients. The presence of D-pen-alb in relatively high concentrations throughout the dosage interval contrasts with the low concentrations and rapid elimination of D-pen. Both D-pen and D-pen-alb were also shown to be present at the putative site of drug action (the inflamed synovial joint) in concentrations lower than those in plasma.
Topics: Adult; Aged; Arthritis, Rheumatoid; Chromatography, High Pressure Liquid; Electrochemistry; Humans; Middle Aged; Penicillamine; Protein Binding; Serum Albumin; Serum Albumin, Human; Synovial Fluid
PubMed: 2291865
DOI: 10.1111/j.1365-2125.1990.tb03808.x -
Basic & Clinical Pharmacology &... May 2012Previous studies on animals have revealed that garlic (Allium sativum) is effective in reducing blood and tissue lead concentrations. The aim of this study was to... (Comparative Study)
Comparative Study Randomized Controlled Trial
Previous studies on animals have revealed that garlic (Allium sativum) is effective in reducing blood and tissue lead concentrations. The aim of this study was to investigate therapeutic effects of garlic and compare it with d-penicillamine in patients with chronic lead poisoning. After coordination and obtaining informed consent, clinical examinations and blood lead concentration (BLC) of 117 workers at a car battery industry were investigated. BLC was determined by heated graphite atomization technique of an atomic absorption spectrometer. The workers were randomly assigned into two groups of garlic (1200 μg allicin, three times daily) and d-penicillamine (250 mg, three times daily) and treated for 4 weeks. BLC was determined again 10days post-treatment. Clinical signs and symptoms of lead poisoning were also investigated and compared with the initial findings. Clinical improvement was significant in a number of clinical manifestations including irritability (p = 0.031), headache (p = 0.028), decreased deep tendon reflex (p=0.019) and mean systolic blood pressure (0.021) after treatment with garlic, but not d-penicillamine. BLCs were reduced significantly (p=0.002 and p=0.025) from 426.32±185.128 to 347.34±121.056 μg/L and from 417.47±192.54 to 315.76±140.00μg/L in the garlic and d-penicillamine groups, respectively, with no significant difference (p=0.892) between the two groups. The frequency of side effects was significantly (p=0.023) higher in d-penicillamine than in the garlic group. Thus, garlic seems safer clinically and as effective as d-penicillamine. Therefore, garlic can be recommended for the treatment of mild-to-moderate lead poisoning.
Topics: Adult; Antioxidants; Chelating Agents; Chronic Disease; Double-Blind Method; Female; Garlic; Humans; Lead Poisoning; Male; Middle Aged; Occupational Diseases; Occupational Exposure; Penicillamine; Plant Extracts; Prospective Studies
PubMed: 22151785
DOI: 10.1111/j.1742-7843.2011.00841.x -
British Journal of Pharmacology May 2016Hydrogen sulfide (H2S) is a gasotransmitter produced from L-cysteine through the enzymatic action of cystathionine-γ-lyase (CSE) and/or cystathionine-β-synthase....
BACKGROUND AND PURPOSE
Hydrogen sulfide (H2S) is a gasotransmitter produced from L-cysteine through the enzymatic action of cystathionine-γ-lyase (CSE) and/or cystathionine-β-synthase. D-Penicillamine is the d isomer of a dimethylated cysteine and has been used for the treatment of rheumatoid arthritis. AsD-penicillamine is structurally very similar to cysteine, we have investigated whether D-penicillamine, as a cysteine analogue, has an effect on the H2 S pathway.
EXPERIMENTAL APPROACH
We tested the effect of D-penicillamine (0.01-1 mM) in mouse aortic rings mounted in isolated organ baths and determined whether it could affect H2 S biosynthesis. In particular, we investigated any possible inhibitor or donor behaviour by using recombinant enzyme-based assays and an in vivo approach.
KEY RESULTS
D-Penicillamine, per se, showed little or no vasodilator effect, and it cannot be metabolized as a substrate in place of l-cysteine. However, d-penicillamine significantly reduced L-cysteine-induced vasodilatation in a concentration-dependent manner through inhibition of H2 S biosynthesis, and this effect occurred at concentrations 10 times lower than those needed to induce the release of H2 S. In particular, D-penicillamine selectively inhibited CSE in a pyridoxal-5'-phosphate-dependent manner.
CONCLUSIONS AND IMPLICATIONS
Taken together, our results suggest that D-penicillamine acts as a selective CSE inhibitor, leading to new perspectives in the design and use of specific pharmacological tools for H2 S research. In addition, the inhibitory effect of D-penicillamine on CSE could account for its beneficial action in rheumatoid arthritis patients, where H2 S has been shown to have a detrimental effect.
Topics: Animals; Cystathionine gamma-Lyase; Dose-Response Relationship, Drug; Enzyme Inhibitors; Hydrogen Sulfide; Male; Mice; Penicillamine; Signal Transduction; Structure-Activity Relationship
PubMed: 26890936
DOI: 10.1111/bph.13459 -
Annals of the Rheumatic Diseases Dec 1975
Topics: Humans; Kidney Diseases; Kidney Glomerulus; Penicillamine; Proteinuria
PubMed: 1221947
DOI: 10.1136/ard.34.6.544 -
Proceedings of the Royal Society of... 1977
Review
Topics: Hepatolenticular Degeneration; Humans; Joint Diseases; Penicillamine
PubMed: 122670
DOI: No ID Found -
Proceedings of the Royal Society of... 1977