Cadmium nephrotoxicity

These proteins are important for binding potentially toxic metals such as cadmium, mercury, and lead, which all bind to sulfydryl groups. Consequently, the binding and removal of these metals are protective functions. Metallothioneins are markedly induced by cadmium exposure and the small protein, rich in SH groups, can then sequester the metal. They also may have a protective role in oxidative stress and protect redox-sensitive processes. The protein also has a role in cadmium nephrotoxicity (see chap. 7). 

Goyer RA. Mechanismsof lead and cadmium nephrotoxicity.Toxicol Lett 1989 46 153-176. 

Nordberg GF, Jin T, Nordberg M. Subcellular targets of cadmium nephrotoxicity cadmium binding to renal membrane proteins in animals with or without protective metallothionein synthesis. Environ Elealth Perspect 1994 102 (suppi 3) 191-194. 

Nogawa K. Biologic indicators of cadmium nephrotoxicity in persons with low-level cadmium exposure. Environ Health Perspect 1984 54 163-169. 

Nordberg GF, Jin T, Nordberg M. Subcellular targets of cadmium nephrotoxicity cadmium binding to renal membrane proteins in animals with or without protective metallothionein synthesis. Environ Flealth Perspect 1994 102(suppl 3) 191-194. Fowler BA, Akkerman M. The role of Ca + + In cadmium-induced renal tubular cell Injury.. In Cadmium in the human environment toxicity and carcinogenicity. Nordberg G, Herber R, Alessio L (editors). International Agency for Research on Cancer (lARC) Scientific Publications vol 118, Lyon 1992 p. 271-277. 

Goyee RA (1989) Mechanisms of lead and cadmium nephrotoxicity. Toxicol Lett 46 153-162. 

Bombard, E., D. Maruhn, and M. Rinke. 1999. Time course of chronic oral cadmium nephrotoxicity in Wistar rats Excretion of urinary enzymes. Drug and Chemical Toxicology 22 679-703. 

Bernard A and Lauwerys R. (1990). Early markers of cadmium nephrotoxicity Biological significance and predictive value. Toxocological and Environmental Chemistry, 27, 65-72. 

The sequestration of cadmium by MT is a double-edged sword, i.e., although Cd-MT is relatively inert when stored as an intracellular complex, it becomes a potent nephrotoxicant after reaching the systemic circulation (Cherian et al. 1976 Squibb et al. 1984). Human cadmium nephrotoxicity may be related to Cd-MT exposure, because this may be a major form of cadmium in diet (Maitani et al. 1984). Cadmium salts absorbed from the GI tract or lungs are initially transported to liver, where synthesis of MT is induced. Continual exposure to cadmium results in liver injury with leakage of Cd-MT into the systemic circulation (Dudley et al. 1985). The complex is transported to kidney, filtered, and reabsorbed by the proximal tubule, possibly via a mechanism involving receptor mediated endocytosis (Foulkes... 

In cases of chronic and moderate exposure and in the absence of obvious cadmium nephrotoxicity health effects are less easy to identify. The efficiency of cadmium intake seems to be higher firom inhaled particles than firom ingested forms (see Section 3.1), but this parameter depends on many others, including the... 

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). 

Liu, X.Y., T.Y. Jin, G.F. Nordberg, S. Ranner, M. Sjostrom, and Y. Zhou. 1992. A multivariate study of protective effects of Zn and Cu against nephrotoxicity induced by cadmium metallothionein in rats. Toxicol. Appi. Pharmacol. 114 239-245. 

Primary renal cell culture has been utilized to study a number of nephrotoxic agents including mercuric chloride (Inamoto et al., 1976), cadmium (Cherian, 1982), lead (McLachlin et al., 1980), cisplatin (Tay et al., 1988), aminoglycoside antibiotics... 

Toxicology. Cadmium oxide fume is a severe pulmonary irritant cadmium dust also is a pulmonary irritant, but it is less potent than cadmium fume because it has a larger particle size. Chronic exposure is associated with nephrotoxicity. Several inorganic cadmium compounds cause malignant tumors in animals. 

The binding of cadmium to metallothionein decreases toxicity to the testes but increases the nephrotoxicity, possibly because the complex is preferentially, and more easily, taken up by the kidney than the free metal. Dosing animals with the cadmium-metallothionein complex leads to acute kidney damage, whereas exposure to single doses of cadmium itself does not. 

Renal Effects. Occupational exposure to silver metal dust has been associated with increased excretion of a particular renal enzyme (N-acetyl-p-D glucosaminidase), and with decreased creatinine clearance (Rosenman et al. 1987). Both of these effects are diagnostic of marginally impaired renal function. However, the workers in this study were also exposed to cadmium, which was detected in the urine of 5 of the 27 workers studied. Cadmium is known to be nephrotoxic differentiation of the effects of the two metals in the kidney is not possible with the data presented. Therefore, no conclusion can be drawn regarding renal effects of silver based on this study. 

Liu JX, Nordberg GF. 1995. Nephrotoxicities of aluminum and/or cadmium-metallothionein in rats Creatinine excretion and metabolism of selected essential metals. Pharmacol Toxicol 77 155-160. 

Nicholson JK, Kendall MD, Osborn, D. 1983. Cadmium and nephrotoxicity. Nature 304 633-635. 

A classic example of essential metal deficiency resulting from nonessential metal exposure is Itai itai disease. Cadmium pollution in the Jinzu River basin in Japan resulted in severe nephrotoxicity in approximately 184 people. Renal tubule damage caused excessive loss of electrolytes and small proteins from the urine. In severe cases, urinary Ca loss was so severe that bone Ca was mobilized, resulting in osteomalacia. Renal tubular defects persisted for life and induced hypophosphatemia, hyperuricemia, and hyperchloremia, which are characteristic biochemical features of Itai-itai disease (see Section 21.6.1). 

Exposures to chemical substances such as carbon tetrachloride, 1,1-dichloroeth-ylene, paradichlorobenzene, ethylbenzene, monochlorobenzene, tetrachloroethyl-ene, toluene, 1,1,2-trichloroethane, xylenes, cadmium, and lead are known to canse adverse effects on the kidney. The kidney is unusually susceptible because of its role in filtering harmful substances from the blood. Some of these toxicants canse acnte injury to the kidney, while others produce chronic changes that can lead to end-stage renal failure or cancer. Furthermore, evaluation of the nephrotoxicity of complex industrial waste mixtures with organic chemicals and metals reqnires more stndies. 

Metabolomics has made remarkable inroads into the environmental research community. Here, a major emphasis is to understand the impact that environmental stress, such as pollution and climate change, has on wildlife. Indeed, many government organizations monitor the prevalence of pollutants in certain species of wildlife as indicators of the exposure risk within the environment. Studies of Japanese medaka have been conducted to investigate the effects of trichloroethylene, a common environmental pollutant, and the pesticide dinoseb, on the development of fish embryos (44, 45). Similarly, cadmium toxicity has been examined in the bank vole and rat and has revealed changes in lipid metabolism that preceded classical nephrotoxicity (46, 47). Another study investigated the effects of environmental toxins on earthworms (48). In particular, the analysis of earthworm tissue extracts by NMR spectroscopy identified maltose as a potential biomarker for ecotoxicity within a metal-contaminated site. 

Cadmium is an environmental and occupational pollutant that is associated with nephrotoxicity (1) and bone toxicity (2) even low concentrations can impair renal function and/or increase bone fragihty. Cadmium is also an adulterant in infant formulas and weaning foods. 

Roels HA, Hoet P, Lison D. Usefulness of biomarkers of exposure to inorganic mercury, lead, or cadmium in controlling occupational and environmental risks of nephrotoxicity. Ren Fail. 1999 May-Jul 21(3-4) 251-62. 

Thevenod F. Nephrotoxicity and the proximal tubule. Insights from cadmium. Nephron Physiol 93 p87-93,2003. 

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