Nephrotoxicity copper

In mammals, cadmium inhibits copper absorption across the intestinal mucosa (Aaseth and Norseth 1986). Intercorrelations of copper with cadmium and zinc in livers of polar bears (Ursus maritimus) are probably mediated by metallothioneins, which may contain all three metals (Braune etal. 1991). In rats, copper protects against nephrotoxicity induced by cadmium, provided that copper is administered 24 h prior to cadmium insult. Specifically, rats given 12.5 mg Cu/kg BW by way of subcutaneous injection 24 h before receiving 0.4 mg Cd/kg BW — when compared to a group receiving Cd alone — did not have excessive calcium in urine and renal cortex or excessive protein in urine. Thus, 2.8 mg Cu/kg BW protects against 0.25 mg Cd/kg BW (Liu et al. 1992). 

D-penidllamine can promote the elimination of copper (e.g., in Wilson s disease) and of lead ions. It can be given orally. Two additional uses are cystinu-ria and rheumatoid arthritis. In the former, formation of cystine stones in the urinary tract is prevented because the drug can form a disulfide with cysteine that is readily soluble. In the latter, penicillamine can be used as a basal regimen (p. 320). The therapeutic effect may result in part from a reaction with aldehydes, whereby polymerization of collagen molecules into fibrils is inhibited. Unwanted effects are cutaneous damage (diminished resistance to mechanical stress with a tendency to form blisters), nephrotoxicity, bone marrow depression, and taste disturbances. 

Kays SE, Crowell WA, Johnson MA. Cephaloridine nephrotoxicity is potentiated by selenium deficiency but not by copper deficiency in rats. J Nutr 1992 122 1232-1241. 

Metals A wide range of metals induce nephrotoxicity in humans and/or in animal models (Table 5). Some of these metals (e.g., iron, cobalt, copper) are essential elements required for normal body function, while others can be useful in treating diseases. For example, gold salts are useful in treating rheumatoid arthritis lithium salts are indicated for the treatment of manic-depressive illness and aluminum and bismuth salts are available to treat indigestion and stomach aches. However, exposure to these and other metals can occur from environmental sources and in excessive concentrations, can lead to nephropathy. 

Pabla N et al (2009) The copper transporter Ctrl contributes to cisplatin uptake by renal tubular cells during cisplatin nephrotoxicity. Am J Physiol Renal Physiol 296(3) F505-F511... 

Because of its nephrotoxicity causing the Itai-Itai disease in humans, its teratogenic effects, its interactions with iron, copper and zinc, and its potentially existing can-cerogenic effects, cadmium (Cd) belongs to... 

Koropatnick J, Leibbrandt M, Cherian MG (1989) Organ-specific metallothionein induction in mice by x-irradiation. Radiat Res 119 356-365 Lehman-McKeeman LD, Kershaw WC, Klaassen CD (1991) Species differences in metallothionein regulation a comparison of the induction of isometallothioneins in rats and mice. In Klaassen CD, Suzuki KT (eds) Metallothionein in biology and medicine, CRC, Boca Raton, pp 121-132 Lui EMK (1987) Metabolism of copper and zinc in the liver and bone of perinatal guinea pig. Comp Biochem Physiol 86 173-183 Maitani T, Cuppage FE, Klaassen CD (1988) Nephrotoxicity of intravenously injected cadmium-metallothionein critical concentration and tolerance. Fund Appl Toxicol 10 98-108... 

Cadmium has a diversity of toxic effects including nephrotoxicity, carcinogenicity, teratogenicity, and endocrine and reproductive toxicities. Although cadmium is not essential for growth and development in mammals, it generally followes the metabolic pathways of the essential elements zinc and copper. 

Recently Clarke et al. have advanced the proposal that antitumor RudDammine complexes may excert their action by redox cycling in the presence of oxygen and a reducing agent with formation of active oxygen species which cleave DNA. The most prominent member of the metal group is cis-DDP. Evidence for electron transfer is provided by electrochemical behavior , radiosensitization" and nephrotoxicity s 2-74, Anticancer activity is displayed by a number of other metals and metalloids in compound form s -- . The possibility exists that the ultimate active forms of the various metals may be the DNA complexes, for example, with copper s and ruthenium . ET and oxy radical formation are known to occur with enzymes that contain copper s . 

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