Copper hepatic accumulation

In young swine, addition of 0.5% ascorbic acid to a diet containing a toxic amount of copper, 250 mg/kg of diet, reduced the anemia that was the toxic manifestation of copper excess, and reduced hepatic accumulation of copper (53). 

Toxic milk (tx) is a recessive mutation in mice which causes hepatic accumulation of copper that begins during the third postnatal week. By 6 months of age, the copper... 

Hepatic accumulations of copper may occur with any biliary excretion disturbance, as the biliary tract is the major route of copper excretion in humans. Sometimes, patients with primary biliary cirrhosis may have as high hepatic copper as in WD. Evidently, high liver copper deposits in biliary cirrhosis are secondary to a different pathological cause than WD, and the removal of copper using D-penicillamine will not benefit the cirrhotic patient. 

Wilson s disease is another autosomal recessive disease leading to cirrhosis. Protein abnormalities result in excessive copper deposition in body tissues. The faulty protein is responsible for facilitating copper excretion in the bile, so copper accumulates in hepatic tissue. High copper levels within hepatocytes are toxic, and fibrosis and cirrhosis may develop in untreated patients. Those with Wilson s disease usually present with symptoms of liver or neurologic disease while still in their teens. 

Wilson s disease is an autosomal recessive disorder characterized by the accumulation of copper in liver and brain [21]. Hepatic involvement may result in liver cirrhosis and hepatic cancer. The deposition of copper in the basal ganglia results in a variety of movement disorders, including... 

Treated rats had 1000 mg/kg FW liver (vs. 4.7 in controls) lowered hemoglobin, hematocrit, and red cell counts mean survival time of 67 days hepatic and renal histopathology Dose-time-dependent increase in copper concentrations in liver, spleen, and lung little accumulation in muscle and skin. Reduced growth at 2.5 and 3.75 mg/kg BW daily reduced survival at 3.75 mg/kg BW. Maximum copper concentrations recorded, in mg/kg FW (vs. saline controls,) were 710 in liver (<5), 212 in kidney (<10), 7 in lung (<1.5), 27 in spleen (<2.0) 6 in bone (<2.0) and 2.2 in testes (<1.6) Increased serum ceruloplasmin and white blood cell number... 

Sugawara, N. and C. Sugawara. 1994. A copper deficient diet prevents copper accumulation and dysfunction in Long-Evans Cinnamon (LEC) rats with an abnormal copper metabolism and hereditary hepatitis. Arch. Toxicol. 69 137-140. 

Thiram and other dithiocarbamates are metabolic poisons. The acute effects of thiram are very similar to that of carbon disulfide, supporting the notion that the common metabolite of this compound is responsible for its toxic effects. The exact mechanism of toxicity is still unclear, however it has been postulated that the intracellular action of thiram involves metabolites of carbon disulfide, causing microsome injury and cytochrome P450 disruption, leading to increased heme-oxygenase activity. The intracellular mechanism of toxicity of thiram may include inhibition of monoamine oxidase, altered vitamin Bg and tryptophan metabolism, and cellular deprivation of zinc and copper. It induces accumulation of acetaldehyde in the bloodstream following ethanol or paraldehyde treatment. Thiram inhibits the in vitro conversion of dopamine to noradrenalin in cardiac and adrenal medulla cell preparations. It depresses some hepatic microsomal demethylation reactions, microsomal cytochrome P450 content and the synthesis of phospholipids. Thiram has also been shown to have moderate inhibitory action on decarboxylases and, in fish, on muscle acetylcholinesterases. 

Wilson s disease is an autosomal recessive disease of copper metabolism. It has a prevalence of 1 in 30,000 live births in most populations. The disease has a highly variable clinical presentation. It is characterized by impairment of biliary copper excretion, decreased incorporation of copper into ceruloplasmin, and accumulation of copper in the liver and, eventually, in the brain and other tissues. The biochemical findings include low serum ceruloplasmin, high urinary copper excretion, and high hepatic copper content. Some patients have normal serum cerulo-plasmia levels, and heterozygous individuals do not consistently show reduced levels of this protein. 

Idiopathic (Indian) childhood cirrhosis is a disorder of progressive liver failure in early childhood, with marked accumulation of hepatic copper usually resulting in death from liver failure. Although the etiology of this disorder in unknown, in all such cases the serum ceruloplasmin is elevated, suggesting a defect in biliary copper excretion beyond the point of entry into the secretor pathway. Originally described in infants... 

Li Y, Togashi Y, Sato S, Emoto T, Kang J-H, Takeichi N, Kobayashi H, Kojima Y, Une Y and Uchino J (1991) Spontaneous hepatic copper accumulation in Long-Evans Cinnamon rats with hereditary hepatitis. J Clin Invest 87 1858-1861. 

Copper detoxifying mechanisms in fishes include the induction of metallothioneins, allowing copper retention for weeks or months after absorption without producing toxic effects. Hepatic metallothionein contents of individual fishes usually reflect the accumulation of copper in that organ. This strongly supports the use of metallothionein as an indicator of copper stress. 

Hatano R, Ebara M, Fukuda H, et al. Accumulation of copper in the liver and hepatic injury in chronic hepatitis C. J Gastroenterol Hepatol 2000 15 786-791. 

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