Liver, cadmium toxicity

Cadmium occurs only in one valency state (2 ) and does not form stable alkyl compounds or other organometallic compounds of known toxicological significance. Cadmium initially is distributed to the liver and then redistributes slowly to the kidney as cadmium-metallothionein (Cd-MT), with 50% of the total-body burden in the liver and kidney after distribution. Cadmium and several other metals induce the expression of metallothionein, a cysteine-rich protein with high affinity for metals such as cadmium and zinc. Metallothionein protects cells against cadmium toxicity by preventing the interaction of cadmium with other proteins. 

In animal studies, decreased zinc status also contributes to lead and cadmium toxicity. In studies with rats, Cerklewski and Forbes (1976) demonstrated that an increase of zinc in the diet decreased the tissue lead levels and reduced other indicators of lead toxicity. Cerklewski (1979) also demonstrated that high levels of zinc fed to pregnant rats resulted in significantly lower levels of lead in the blood and liver of the rat pups. Using Japanese quail, Jacobs et al. (1977) reported that supplemental zinc markedly decreased concentrations of cadmium in the liver, kidney and small intestine, while Fox et al. (1979) showed that marginally adequate levels of dietary zinc markedly increased retention of cadmium in the duodenum, jejunum, ileum and liver as compared with zinc-supplemented birds. The association between increased lead burdens and lower serum zinc levels in children was reported by Markowitz and Rosen (1981). However, the mean levels of serum zinc in the children with elevated blood lead levels were not considered to be outside the lower limits of normal for plasma cited by Hambidge (1977). 

Bakka A, Samarawickrama GP, Webb M (1981) Metabolism of zinc and copper in the neonate Effect of cadmium administration during late gestation in the rat on the zinc and copper metabolism of the newborn. Chem.-Biol. Interact. 34 161-171 Bakka A, Webb M (1981) Metabolism of zinc and copper in the neonate Changes in the concentrations and contents of thionein-bound Zn and Cu with age in the livers of the newborn of various mammalian species. Biochem. Pharmacol. 30 721-725 Bell JU (1980) Induction of hepatic metallothionein in the immature rat following administration of cadmium. Toxicol. Appl. Pharmcol. 54 148-155 Bremner J (1978) Cadmium toxicity Nutritional influences and the role of metallothionein. Wld. Rev. Nutr. Diet. 32 165-197... 

Stoeppler M (1991) Cadmium. In Merian E (ed) Metals and their compounds in the environment. VCH, New York, pp 803-851 Stoll R, White J, Miya T, Bousquet W (1976) Effects of cadmium on nucleic acid and protein synthesis in rat liver. Toxicol Appl Pharmacol 37 61-74 Stowe HD, Wilson M, Goyer RA (1972) Clinical and morphological effects of oral cadmium toxicity in rabbits. Arch Pathol 94 389-405 Sunderman FW Jr (1978) Carcinogenic effects of metals. Fed Proc 37 40-46 Sunderman FW Jr, Barber AM (1988) Finger loops, oncogenes, and metals. Ann Clin Lab Sci 18 267-288... 

Cadmium is extremely toxic and accumulates in humans mainly in the kidneys and liver prolonged intake, even of very small amounts, leads to dysfunction of the kidneys. It acts by binding to the —SH group of cysteine residues in proteins and so inhibits SH enzymes. It can also inhibit the action of zinc enzymes by displacing the zinc. 

Cadmium is nutritionally non-essential, toxic and a ubiquitous environmental pollutant. It is found in leafy vegetables, grains and cereals, and since it is present in substantial amounts in tobacco leaves, cigarette smokers on a packet a day can easily double their cadmium intake. It has a long biological half-life (17-30 years in man), accumulates in liver and kidneys and its toxicity involves principally kidney and bone (Goyer, 1997).While Cd interferes primarily with calcium, it also interacts with zinc and can induce the synthesis of metallothionein. Cadmium bound to metallothionein in liver or kidney is thought to be non-toxic, but cadmium in plasma... 

Chromium has proved effective in counteracting the deleterious effects of cadmium in rats and of vanadium in chickens. High mortality rates and testicular atrophy occurred in rats subjected to an intraperitoneal injection of cadmium salts however, pretreatment with chromium ameliorated these effects (Stacey et al. 1983). The Cr-Cd relationship is not simple. In some cases, cadmium is known to suppress adverse effects induced in Chinese hamster (Cricetus spp.) ovary cells by Cr (Shimada et al. 1998). In southwestern Sweden, there was an 80% decline in chromium burdens in liver of the moose (Alces alces) between 1982 and 1992 from 0.21 to 0.07 mg Cr/kg FW (Frank et al. 1994). During this same period in this locale, moose experienced an unknown disease caused by a secondary copper deficiency due to elevated molybdenum levels as well as chromium deficiency and trace element imbalance (Frank et al. 1994). In chickens (Gallus sp.), 10 mg/kg of dietary chromium counteracted adverse effects on albumin metabolism and egg shell quality induced by 10 mg/kg of vanadium salts (Jensen and Maurice 1980). Additional research on the beneficial aspects of chromium in living resources appears warranted, especially where the organism is subjected to complex mixtures containing chromium and other potentially toxic heavy metals. 

Nickel may be a factor in asbestos carcinogenicity. The presence of chromium and manganese in asbestos fibers may enhance the carcinogenicity of nickel (USEPA 1980), but this relation needs to be verified. Barium-nickel mixtures inhibit calcium uptake in rats, resulting in reduced growth (WHO 1991). Pretreatment of animals with cadmium enhanced the toxicity of nickel to the kidneys and liver (USPHS 1993). Simultaneous exposure to nickel and cadmium — an industrial situation... 

Selenium is readily available in a variety of foods including shrimp, meat, dairy products, and grains, with a recommended daily intake of 55 to 70 jug. It occurs in several forms with Se+6 being biologically most important. Selenium is readily absorbed by the intestine and is widely distributed throughout the tissues of the body, with the highest levels in the liver and kidney. It is active in a variety of cellular functions and interacts with vitamin E. Selenium appears to reduce the toxic effects of metals such as cadmium and mercury and to have anticarcinogenic activity. Selenium produces notable adverse effects both in deficiency and excess thus recommended daily intake for adults is approximately 70 Jg/day but should not exceed 200 pg/day. 

Numerous substances detected in drinking waters are known to induce toxicity but usually at dose levels much higher than those found in water. Nitrates or nitrites can cause infant methemoglobinemia, lead can affect the hematopoetic or nervous system, cadmium can cause renal damage, and some organohalogens may cause liver toxicity (12). 

Because of the ease with which dimercaptopropanol can be broken down in the body there is a danger that chelation, followed by breakdown, will simply result in the translocation of the metal ions to other tissues such as brain or liver. High doses of dimercaptopropanol can adversely affect a number of essential metal-activated enzymes, such as catalase, carbonic anhydrase and peroxidase, and also produce dangerous systemic effects. Dimercaptopropanol cannot be used to remove cadmium because its cadmium complex is toxic to kidney tissue54). 

Cadmium is a cumulative toxicant with a biologic half-life of up to 30 years in humans. More than 70% of the cadmium in the blood is bound to red blood cells accumulation occurs mainly in the kidney and the liver, where cadmium is bound to metallothionein. In humans the critical target organ after long-term exposure to cadmium is the kidney, with the first detectable symptom of kidney toxicity being an increased excretion of specific proteins. 

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