• Tuberculosis and Respiratory Diseases
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• v.42 no.2
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• pp.184-205
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• 1995

Background: Pulmonary toxicity by bleomycin has multiple mechanisms including direct tissue toxicity due to oxygen-derived free radicals and indirect toxicity through amplification of pulmonary inflammation. To evaluate the effect of chelators or free radical scavenger to lung damage induced by bleomycin, penicillamine as a copper chelator, deferoxamine as an iron chelator and vitamin E as a free radical scavenger were administered. Methods: Two hundred Wistar rats were divided into five groups: Control, bleomycin treated, bleomycin-penicillamine treated, bleomycin-deferoxamine treated, and bleomycin-vitamin E treated groups. Rats sacrificed on day 1, day 3, day 4, day 7, day 14, and day 28 after treatment. Bronchoalveolar lavage, light microscopic and immunohistologic studies for type I, III, IV collagens, fibronectin, laminin and NBD phallicidin were evaluated. Results: There was a significant increase in the total cell counts of bronchoalveolar lavage on day 1 from all treated animals and vitamin treated group showed an abrupt decrease in total cell counts with decrease of neutrophils on day 3. Bleomycin-vitamin E treated group had the least histologic changes such as pulmonary fibrosis. The alveolar basement membranes were positive for type IV collegen and laminin. Basement membranes of bleomycin, bleomycin-penicillamine, or bleomycin-deferoxamine treated groups were disrupted and fragmented on day 4 or 7. The bleomycin-vitamin E treated group had intact basement membranes until day 28. Conclusion: Bleomycin-induced pulmonary fibrosis was related to the severity of acute injury to oxygen radicals or activation of neutrophils and disruption of basement membrane. Vitamin E seemed to be the most effective antioxidant in the inhibition of bleomycin-induced pulmonary injury and fibrosis.

• Journal of Pharmaceutical Investigation
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• v.20 no.2
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• pp.73-78
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• 1990

A sensitive fluorometric method using 9-fluorenylmethyl pentafluorophenyl carbonate (FMPC) as the fluorescent labeling agent was developed to determine D-penicillamine (D-PA). The fluorophore had excitation and emission wavelengths of 260 nm and 313 nm, respectively. After derivatization, the fluorescent product was separated, and quantified by spectrofluorometry. The derivative was highly fluorescent and stable. Optimum condition for the reaction was investigated. A linear response was obtained over the range of $4.0{\times}10^{-7}-5.0{\times}10{-6}\;M$ with the correlation coefficient of 0.999 (n=6). The procedure described was successfully applied to the determination of the dosage forms of capsule with the recovery of $98.62{\pm}0.57%$ (150 mg), $98.36{\pm}0.57%$, (250 mg).

• Journal of the Korean Chemical Society
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• v.35 no.4
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• pp.429-431
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• 1991

• Environmental Analysis Health and Toxicology
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• v.7 no.1_2
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• pp.53-57
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• 1992

Amount of lead burden in a tissue reflects poisoning of lead in that tissue, so is the removal of lead directly connected to curement of lead poisoning. The purpose of present study was to investigate the relative effects of penicillamine and thiamine tetrahydrofurfuryl disulfide (TTFD) or thiamine propyl disulfide (TPD) in the removal of lead from rat brain tissue treated with excessive lead. Wistar rat pups of both sexes were used in this experiment. Within 1 day of parturition, experimental mothers nursing their pups as well as rat pups were given drinking water containing 0.2% lead acetate, TTFD 20mg/1.2 L (2 mg/kg/day), TPD 20 mg/1.2 L (2mg/kg/day), penicillamine 40 mg/1.2 L (40 mg/kg/day), 0.2% lead acetate+TTFD 20mg/1.2 L (2 mg/kg/day), 0.2% lead acetate+ TPD 20 mg/1.2 L (2 mg/kg/day) or 0.2% lead acetate+ penicillamine 40 mg/1.2 L (40 mg/kg/day) ad libitum, throughout the entire period of experiment. Rat pups in the control group received normal tap water. The animals were sacrificed by decapitation on the day when they become 2 or 8 weeks of age. Brains were dissected into five regions: telencephalon, diencephalon, midbrain, pons/medulla and cerebellum. The dissected brain tissues were lyophillized and then solubilized by acid mixture (nitric acid + sulfuric acid). Lead levels in the solubilized brain tissues were measured by the inductively coupled plasma. In lead-exposed rats, lead levels were significantly higher than those of control group in all brain legions, lead levels in brain regions of TTFD or TPD group were generally lower than those of control group. The simultaneous administration of lead with TTFD or TPD to animals caused significant decrement of lead from all brain regions. In the elimination of lead from brain regions, effectiveness of TTFD or TPD was equivalant to penicillamine.

• Journal of Veterinary Clinics
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• v.28 no.2
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• pp.249-253
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• 2011

A 4-year-old intact female American Cocker Spaniel presented with lack of appetite, shivering, and abdominal distension. It was initially diagnosed with chronic hepatitis with cirrhosis, by serum chemistry, radiography, ultrasonography, and histopathologic examination following liver biopsy. Abundant copper granules were detected in most hepatocytes with rhodanine stain, with hepatic copper concentration at 1460 ppm (reference range: <400 ppm). Based on these findings, copper-associated hepatitis with cirrhosis was diagnosed and successfully managed with long-term D-penicillamine, s-adenosylmethionine, biphenyl-dimethyl-dicarboxylate and supportive care. The spaniel died 35 months after diagnosis.

• Bulletin of the Korean Chemical Society
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• v.24 no.3
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• pp.350-356
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• 2003

The mechanism of the decomposition of a bronchodilator, S-nitroso-N-acetyl-D,L-penicillamine (SNAP) by a bronchoconstrictor, aqueous sulfite, has been investigated in detail. The decomposition was studied using a conventional spectrophotometer at 336 nm over the ranges: 0.010 ≤ $[S^{IV}]_T$ ≤ 0.045 mol $dm^{-3}$, 3.96 ≤ pH ≤ 6.80 and 15.0 ≤ θ≤ 30.0 ℃, 0.60 ≤ I ≤ 1.00 mol $dm^{-3}$, and at ionic strength 1.00 mol $dm^{-3}$ (NaCl). The rate of reaction is dependent on the total sulfite concentration and pH in a complex manner, i.e., $k_{obs}\;=\;k_1K_2[S^{IV}]_T/ ([H^+]\;+\;K_2)$. At 25.0 ℃, the second order rate constant, $k_1$, was determined as $12.5\;{\pm}\;0.15\;mol^{-1}\;dm^3\;s^{-1}$. ${\Delta}H^{neq}\;=\;+32\;{\pm}\;3 kJ\;mol^{-1}\;and\;{\Delta}S^{\neq}\;=\;-138\;{\pm}\;13\;J\;mol^{-1}K^{-1}$. The N-nitrosohydroxylamine-N-sulfonate ion was detected as an intermediate before the formation of any of the by-products, namely, N-acetyl-D,L-penicillamine. The effect of concentration of aqueous copper(Ⅱ) ions on this reaction was also examined at pH 4.75, but there was no dependence on $[Cu^{2+}]$. In addition, the $pK_a$ of SNAP was determined as 3.51 ± 0.06 at 25.4 ℃ [I = 1.0 mol $dm^{-3}$ (NaCl)].

• Bulletin of the Korean Chemical Society
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• v.25 no.4
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• pp.517-524
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• 2004

Two simple and sensitive spectrophotometric methods were developed for the determination of carbocisteine, penicillamine, ethionamide and thioctic acid in bulk and in their pharmaceutical preparations using alkaline potassium permanganate as an oxidizing agent. The first one involves determination of ethionamide and thioctic acid by spectrophotometric investigation of the oxidation reaction of the two drugs. The second method involves determination of carbocisteine and penicillamine by kinetic studies of the oxidation reaction of these two drugs at room temperature for a fixed time of 20 minutes. The absorbance of the colored manganate ions was measured at 610 nm in both methods. 1-10 ${\mu}$g/mL of ethionamide and thioctic acid could be etermined by the spectrophotometric method with detection limits of 0.11 and 0.089 ${\mu}$g/mL for the two drugs respectively. 2-10 ${\mu}$g/mL of carbocisteine and penicillamine could be determined by the kinetic method with detection limits of 0.14 and 0.21 ${\mu}$g/mL respectively. The two methods were successfully applied for the determination of these drugs in their dosage forms.

• Journal of Environmental Health Sciences
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• v.17 no.2
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• pp.95-101
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• 1991

Lead acetate solution were intraperitoneally injected to rats of average body weight 220g to cause lead poisoning. Antidotes were orally administered using catheter to the rats and the urine was collected after 24 hours. ALA in the urine were determined by U. V. spectrophotometer. Antidotes used in this experiment were the water extracts of scutellaria radix and D-penicillamine solution. ALA in the urine was determind by Wada method. It was found that ALA content in the urine was decreased after oral administration of water extracts of scutellaria radix and D-penicillamine solution. In this study it is believed that water extract of suctellaria radix could be used as an excellent antidate in lead poisoning.

• Journal of Preventive Medicine and Public Health
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• v.11 no.1
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• pp.76-82
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• 1978

In order to study the change of laboratory parameters of lead poisoning, 8 persona who had not been treated previously for lead poisoning (Group 1 and 6 persons who had been inadequately treated for few months for chronic lead poisoning at local clinic (Group 2) were examined. They had occupational exposure to lead for 3 to 18 years (mean, 7.6). In group 1 blood lead, urine lead, urine coproporphyrin and ${\delta}$-aminolevulinic acid levels before our treatment exceeded the critical levels of lead poisoning. In group 2 urine lead level exceeded but blood lead, urine coproporphyrin and ${\delta}$-aminolevulinic acid levels were within normal limits. All of them were treated with D-penicillamine for 4 months as inpatients at Industrial Accident Hospital. The dose of D-penicillamine was the same in all patients; 600 mg per day p.o. and the chelating agent was administer every other week. For laboratory analysis, 24 hour urine and 10 gm of whole blood were collected every 1 month on last day of non-administration period. The results were as follows: 1. It was found that urine lead level was decreased below the cirtical level of lead poisoning after 4 month's treatment with D-penicillamine and blood lead level was decreased more progressively below the critical level after 1 month treatment. 2. Urine coproporphyrin and ${\delta}$-aminolevulinic acid levels were decreased progressively to normal range after 1 month treatment. 3. Two months after treatment, blood lead, urine lead, urine coproporphyrin and ${\delta}$-aminolevulinic acid levels showed some increasing trends. 4. Urine lead level should be checked in a person who had been inadequately treated with chelating agents because blood lead, coproporphyrin and ${\delta}$-aminolevulinic acid might be in normal range.

• Bulletin of the Korean Chemical Society
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• v.11 no.4
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• pp.281-286
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• 1990

The kinetics and mechanism of reduction of Cu(II) with an excess D-penicillamine have been examined at pH = 6.2 and 0.60M in ionic strength. The reaction at the initial stage is biphasic with a rapid complexation process to give "red" transient complex of $[Cu(II)(pen)_2]^2$- that is partially reduced to another transient "brown" intermediate. The "brown" intermediate is finally reduced to diamagnetic "yellow" complex, $[Cu(I)(Hpen)]_n$. The final reduction process is pseudo-first order in ["brown" transient] disappearance $with {\kappa} = {{\kappa}_{3a} + {\kappa}_{3b}[pen]^{2-}},$ where ${\kappa}_{3a} = (5.0{\pm}0.8){\times}10^{-3}sec^{-1}$ and ${\kappa} = (0.14{\pm}0.02) M^{-1}sec^{-1}$ at $25^{\circ}C$. The activation parameters for the $[H_2pen]$-independent and $[H_2pen]$-dependent paths are ${\Delta}H^{\neq} = (52{\pm}5)kJmol^{-1},$ and ${\Delta}S^{\neq} = ( - 27{\pm}3)JK^{-1}mo^{l-1},$ and ${\Delta}H^{\neq} = (56{\pm}2)kJmol^{-1}$ and ${\Delta} S^{\neq} = ( - 18{\pm}0.7)JK^{-1}mol^{-1}$ respectively. The nature of "brown" intermediate is not clearly identified, but this intermediate seems to be in the mixed-valence state, judging from the kinetic and spectroscopic informations.