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Clinical Pharmacology and Therapeutics Sep 1981The kinetic characteristics of penicillamine are reported in four fasting subjects after four oral doses each. On late test days, tow of the subjects received an... (Comparative Study)
Comparative Study
The kinetic characteristics of penicillamine are reported in four fasting subjects after four oral doses each. On late test days, tow of the subjects received an additional single dose 30 min after a large breakfast. On subject originally included in the study had to drop out because of gastrointestinal disturbances following each of two single doses of penicillamine. The fasting plasma levels of penicillamine observed in this study displayed an unusual double peak in the plasma levels after single doses. Individual subjects had consistent plasma level patterns for each of the four single doses but there was marked intersubject variability in patterns and kinetic parameters. The half-life of unchanged penicillamine ranged from 1.66 to 3.15 hr and the apparent plasma clearance ranged from 530 to 2300 ml/min. The administration of penicillamine following a large breakfast caused a reduction in the area under the penicillamine plasma concentration-time curve corresponding to a decrease in the extent of absorption of unchanged penicillamine.
Topics: Adult; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Eating; Fasting; Female; Half-Life; Humans; Kinetics; Male; Metabolic Clearance Rate; Penicillamine
PubMed: 7273605
DOI: 10.1038/clpt.1981.180 -
Biomedicine & Pharmacotherapy =... Feb 2023There are considerable evidence of reproductive impairment in male organisms with Wilson disease (WD). The purpose of this study was to observe spermatogenesis,...
Glutathione improves testicular spermatogenesis through inhibiting oxidative stress, mitochondrial damage, and apoptosis induced by copper deposition in mice with Wilson disease.
BACKGROUND AND OBJECTIVE
There are considerable evidence of reproductive impairment in male organisms with Wilson disease (WD). The purpose of this study was to observe spermatogenesis, mitochondrial damage, apoptosis, and the level of oxidative stress in the testes of Wilson disease model TX mice, and to observe the effect and mechanism of glutathione on testicular spermatogenesis.
METHODS
Mice were divided into a normal control group (control group), Wilson disease model TX mice group (WD group), penicillamine-treated TX mice group (penicillamine group) and glutathione-treated TX mice group (glutathione group). Testicular coefficient, histomorphology of testis and epididymis, number of spermatozoa, apoptosis of spermatogenic cells and expression of apoptosis-related proteins were observed. Ultrastructural analysis of mitochondria and mitochondrial membrane potential (MMP) monitored using JC-1 dye were used to detect mitochondrial damage. The levels of malondialdehyde (MDA), glutathione (GSH), catalase (CAT), and reactive oxygen species (ROS) in testicular cells were measured to assess oxidative stress.
RESULTS
Testicular coefficient did not change in mice with Wilson disease. However, the tissue structure of the testicular seminiferous tubules was damaged, and the number of spermatozoa in the epididymal lumen was significantly reduced in WD group. The apoptosis rate in the testes was significantly increased. The protein expression of the pro-apoptotic proteins Bax and Caspase-3 significantly increased, and the expressions of the anti-apoptotic protein Bcl-2 significantly decreased. The levels of ROS and MDA significantly increased, and the levels of CAT and GSH significantly decreased. Mitochondria with abnormal ultrastructure and the rate of JC-1 positive cells were significantly increased in the WD group. After copper chelation by penicillamine, the structure of the testicular seminiferous tubules and the number of spermatozoa in the epididymal lumen were significantly improved. The number of apoptotic cells was significantly reduced. The levels of Bax and Caspase-3 decreased, and the expression of Bcl-2 increased. The contents of CAT and GSH increased, and the levels of ROS and MDA decreased significantly. The abnormal mitochondria and JC-1 positive cells was significantly decreased. The histomorphology of seminiferous tubules, spermatogenic function, apoptosis rate, apoptosis-related proteins, mitochondrial damage, and oxidative stress in Wilson disease TX mice significantly improved after glutathione treatment.
CONCLUSION
Copper deposition in Wilson disease can lead to oxidative stress injury, mitochondrial damage, and apoptosis in the testis, leading to the impairment of spermatogenesis. Glutathione may improve testicular spermatogenesis in male Wilson disease TX mice by inhibiting copper deposition-induced oxidative stress, mitochondrial damage, and apoptosis.
Topics: Mice; Male; Animals; Testis; Copper; Caspase 3; Reactive Oxygen Species; Hepatolenticular Degeneration; bcl-2-Associated X Protein; Spermatogenesis; Oxidative Stress; Apoptosis; Glutathione; Apoptosis Regulatory Proteins; Penicillamine
PubMed: 36502753
DOI: 10.1016/j.biopha.2022.114107 -
Proceedings of the Royal Society of... 1977
Review
Topics: Administration, Topical; Corneal Ulcer; Humans; Penicillamine
PubMed: 122682
DOI: No ID Found -
Hepatology (Baltimore, Md.) May 2024Trientine (TRI) and D-penicillamine (PEN) are used to treat copper overload in Wilson disease. Their main mode of action is thought to be through the facilitation of...
BACKGROUND AND AIMS
Trientine (TRI) and D-penicillamine (PEN) are used to treat copper overload in Wilson disease. Their main mode of action is thought to be through the facilitation of urinary copper excretion. In a recent study, TRI was noninferior to PEN despite lower 24-hour urinary copper excretion than PEN. We tested whether TRI and/or PEN also inhibit intestinal copper absorption.
APPROACH AND RESULTS
Sixteen healthy volunteers were examined with positron emission tomography (PET)/CT 1 and 15 hours after an oral Copper-64 ( 64 Cu) dose. They then received 7 days of either PEN or TRI (trientine tetrahydrochloride), after which the 64 Cu PET/CT scans were repeated. Venous blood samples were also collected. Pretreatment to posttreatment changes of the hepatic 64 Cu uptake reflect the effect of drugs on intestinal absorption. 64 Cu activity was normalized to dose and body weight and expressed as the mean standard uptake value. TRI (n=8) reduced hepatic 64 Cu activity 1 hour after 64 Cu dose from 6.17 (4.73) to 1.47 (2.97) standard uptake value, p <0.02, and after 15 hours from 14.24 (3.09) to 6.19 (3.43), p <0.02, indicating strong inhibition of intestinal 64 Cu absorption. PEN (n=8) slightly reduced hepatic standard uptake value at 15 hours, from 16.30 (5.63) to 12.17 (1.44), p <0.04.
CONCLUSIONS
In this mechanistic study, we show that TRI inhibits intestinal copper absorption, in addition to its cupriuretic effect. In contrast, PEN has modest effects on the intestinal copper absorption. This may explain why TRI and PEN are equally effective although urinary copper excretion is lower with TRI. The study questions whether the same therapeutic targets for 24-hour urinary excretion apply to both drugs.
Topics: Humans; Penicillamine; Trientine; Copper; Positron Emission Tomography Computed Tomography; Copper Radioisotopes; Hepatolenticular Degeneration; Positron-Emission Tomography
PubMed: 38088886
DOI: 10.1097/HEP.0000000000000708 -
Journal of Medical Toxicology :... Dec 2014Ayurveda, Indian traditional system of medicine, is practiced commonly in South East Asia and in many parts of the world. Many ayurvedic drugs contain heavy metals and...
BACKGROUND
Ayurveda, Indian traditional system of medicine, is practiced commonly in South East Asia and in many parts of the world. Many ayurvedic drugs contain heavy metals and may lead to metal toxicity. Of these, chronic lead poisoning is the most common. Chronic arsenic poisoning following the use of ayurvedic medication, though reported, is rare.
CASE REPORTS
We describe three patients who presented with features of chronic arsenic poisoning following prolonged ayurvedic medication use. The diagnosis of chronic arsenic poisoning was confirmed by high arsenic levels in the blood, urine, hair, and nails in all the three patients and in ayurvedic drug in two patients. The ayurvedic medication was discontinued and treatment with D-penicillamine started. At 6 months after treatment, blood arsenic levels returned to normal with clinical recovery in all of them.
CONCLUSION
Arsenic poisoning following ayurvedic medication is much less common than lead poisoning, though mineral ayurvedic medicines may lead to it. We used D-penicillamine as chelator and all of them recovered. Whether withdrawal of medication alone or D-penicillamine also played a role in recovery is unclear and needs to be assessed.
Topics: Adult; Arsenic Poisoning; Chronic Disease; Female; Humans; Male; Medicine, Ayurvedic; Penicillamine
PubMed: 24696169
DOI: 10.1007/s13181-014-0389-0 -
BMJ Case Reports Dec 2015
Topics: Adult; Biopsy; Chelating Agents; Female; Humans; Penicillamine; Skin Diseases
PubMed: 26643186
DOI: 10.1136/bcr-2015-212482 -
Annals of the Rheumatic Diseases Oct 1980This study has set out to establish whether fenclofenac has an antirheumatic effect in addition to its anti-inflammatory and analgesic activity. The results show that... (Clinical Trial)
Clinical Trial
This study has set out to establish whether fenclofenac has an antirheumatic effect in addition to its anti-inflammatory and analgesic activity. The results show that during the course of a 6-month study the drug improved clinical parameters, including the articular index, early morning stiffness, ring sizes, and grip strength, and produced changes in laboratory measurements such as the levels of C-reactive protein, IgG, and rheumatoid factor.
Topics: Adolescent; Adult; Aged; Arthritis, Rheumatoid; Clinical Trials as Topic; Humans; Middle Aged; Penicillamine; Phenylacetates; Time Factors
PubMed: 7002066
DOI: 10.1136/ard.39.5.473 -
Annals of the Rheumatic Diseases Jul 1991
Review
Topics: Arthritis, Rheumatoid; Drug Therapy, Combination; Gold; Humans; Hydroxychloroquine; Penicillamine
PubMed: 1877859
DOI: 10.1136/ard.50.7.507 -
Proceedings of the Royal Society of... 1977
Review
Topics: Animals; Chelating Agents; Chemical Phenomena; Chemistry, Physical; Disulfides; Humans; Penicillamine; Quinones; Sulfhydryl Compounds; Thiazoles
PubMed: 122675
DOI: No ID Found -
Asian Pacific Journal of Allergy and... Jun 2020Generalised morphea (GM) is a subtype of localised scleroderma that usually manifests with bilateral involvement. Unilateral generalised morphea (UGM) is a rare variant...
Generalised morphea (GM) is a subtype of localised scleroderma that usually manifests with bilateral involvement. Unilateral generalised morphea (UGM) is a rare variant of GM. This is a case report of a Taiwanese girl with UGM over the left side of her body. She presented with hyperpigmentation, tightness, and skin atrophy over the left extremities and trunk. Mild range of motion (ROM) limitation over the left knee was also noted. At the clinic, the patient was given oral prednisolone, oral methotrexate (MTX), and oral D-penicillamine. topical emollient and topical glucocorticoids were also given. The dose of oral prednisolone was tapered gradually. All symptoms were improved under the treatment and regular rehabilitation program. To date, there is very little evidence to form the basis for treatment recommendations. This case report provides a treatment option for UGM in the paediatric group without the use of intravenous methylprednisolone pulse therapy.
Topics: Administration, Oral; Administration, Topical; Child; Emollients; Female; Humans; Hyperpigmentation; Methotrexate; Penicillamine; Prednisolone; Scleroderma, Localized; Skin; Taiwan; Treatment Outcome
PubMed: 30525738
DOI: 10.12932/AP-020818-0387