Penicillamine deprotonations and interactions with copper ions

In aqueous solutions about five times as many penicillamine molecules possess ionized sulfhydryl groups as deprotonated amino groups. That the corresponding ratio for cysteine is two is reaffirmed. N-Acetyl-dl-penicillamine and d-penicillamine react with Cu(II), even in acid solutions, to yield the corresponding disulfide and Cu(I). Cu(I) binds on the average only one sulfhydryl molecule, and a polymeric structure is suggested. A mixed valence state purple species absorbing at 520 nm and stable even in air is formed when approximately equivalent amounts of Cu(I), Cu(II), and d-penicillamine are present in neutral solutions. In the absence of oxygen and in the presence of 0.1 n base d-penicillamine forms a 2:1 complex with Cu(II) that is stable for hours. Absorption and circular dichroism are reported for the above species and the Cu(II) complexes of l-cystinediamide and l-cystinylbisglycine.     

Effect of Penicillamine in Promoting Lead Excretion

A spectrochemical study of the urine and blood of 14 subjects exposed to lead in their work for several years, but without obvious signs of intoxication, was carried out to determine the porphyrin and lead content before and after a provocative dose of 0.9 g. penicillamine, administered on a single day.The average total urinary porphyrin excretion before administration of penicillamine was 0.506 mg. per litre (normal value = 0.274), and after penicillamine administration 0.386 mg. per litre (normal value = 0.274). The average lead excretion before administration of penicillamine was less than 0.013 mg. per litre (normal value = 0.031) and after administration of penicillamine 0.367 mg. per litre (normal value = 0.047).The average erythrocyte porphyrin content was 76.8 μg. % before and 76.95 μg. % after administration of penicillamine—values approximately thrice normal. Blood lead content before administration of penicillamine averaged 7.61 μg. % and after penicillamine 5.68 μg. %.Lead excretion in exposed persons before penicillamine administration was less than in apparently normal persons, while porphyrin levels were higher. The effect of penicillamine is shown by a definite increase in lead excretion (average = 0.406 mg. lead per gram penicillamine administered) and a decrease in porphyrin excretion in the 14 subjects.     

Nephrotoxicity after radionuclide therapies

Radioligand therapies have opened new treatment avenues for cancer patients. They offer precise tumor targeting with a favorable efficacy-to-toxicity profile. Specifically, the kidneys, once regarded as the critical organ for radiation toxicity, also show excellent tolerance to radiation doses as high as 50–60 Gy in selected cases. However, the number of nephrons that form the structural and functional units of the kidney is determined before birth and is fixed. Thus, loss of nephrons secondary to any injury may lead to an irreversible decline in renal function over time. Our primary understanding of radiation-induced nephropathy is derived from the effects of external beam radiation on the renal tissue. With the growing adoption of radionuclide therapies, considerable evidence has been gained with regard to the occurrence of renal toxicity and its associated risk factors. In this review, we discuss the radionuclide therapies associated with the risk of nephrotoxicity, the present understanding of the factors and mechanisms that contribute to renal injury, and the current and potential methods for preventing, identifying, and managing nephrotoxicity, specifically acute onset nephropathies.     

Penicillamine in Rheumatoid Disease: A Long-term Study

Eighty-five patients with rheumatoid disease were treated with penicillamine, and 69 completed more than one year''s treatment. The main reason for discontinuing penicillamine in the 16 patients who withdrew was adverse reaction. The number of adverse reactions, however, declined when patients were given lower maintenance doses of penicillamine. In those who tolerated the drug the results of treatment were good. To prevent side effects the drug should be introduced gradually and maintenance doses should be the lowest which produce a satisfactory response. Urine should be monitored for protein and blood for changes in platelet and white cell counts at frequent intervals throughout treatment.     

Nephrotoxicity of halogenated alkenyl cysteine-S-conjugates

In 1916 a relationship was postulated between the occurrence of aplastic anaemia in cattle and the soy bean meal that they had been fed, which had been extracted with trichloroethylene. The toxic compound was later identified as S-(1,2-dichlorovinyl)-L-cysteine (DCV-Cys). In addition to effects on the hemopoietic system it also produced nephrotoxicity in calves. In rats only renal tubular necrosis was found. Further research demonstrated that other halogenated hydrocarbons produced similar nephrotoxicity. The haloalkenyl cysteine-S-conjugates (Cys-S-conjugates) have extensively been studied; this has provided new insight into the biochemical processes that lead to nephrotoxicity. It has been shown that a combination of transport processes and specific metabolic pathways, resulting in reactive intermediates that bind to cellular macromolecules, makes the kidney vulnerable to the noxious effects of the haloalkenyl Cys-S-conjugates. The first part of this review gives a brief overview of the bioactivation of the haloalkenes; in the second part the present knowledge of the underlying mechanisms of cytotoxicity will be outlined.     

Comparative Nephrotoxicity of Aspirin and Phenacetin Derivatives

Both aspirin and phenacetin derivatives were shown to be nephrotoxic when administered to rats as a single intravenous injection. Phenacetin derivatives tended to produce more severe renal damage and to be nephrotoxic in smaller doses than aspirin derivatives. With the exception of a single derivative, the renal lesions were confined to the proximal convoluted tubule, even after administration of compounds which under other conditions have induced renal papillary necrosis.