Paradigm shift in treatment of Wilson's disease: Zinc therapy now treatment of choice 2005
Zinc therapy has replaced penicillamine as first-line therapy for Wilson's disease. New guidelines reflect the paradigm shift in treatment that has occurred in recent years. In the old paradigm, Wilson's disease was seen as genetic disorder associated with the accumulation of copper in the liver and in other organs once the liver had become overloaded with copper. When left untreated, the disease was regarded as uniformly fatal. The old treatment guidelines advised, ‘decoppering’ with penicillamine because this chelating agent was considered effective in restoring most patients to health. Before the start of treatment, patients were warned that their symptoms could worsen during the first weeks or months of therapy, so as to prevent them from abandoning penicillamine therapy in dismay. In the new paradigm, Wilson's disease is seen as a hereditary disorder associated with copper intoxication. The essence of symptomatic Wilson's disease is poisoning by free copper in the blood, that is, by copper that is not bound to ceruloplasmin. This form of copper is toxic, whereas accumulated copper and copper that is bound to ceruloplasmin or metallothionein is not. The treatment of symptomatic Wilson's disease is no longer aimed at ‘decoppering’, the removal of accumulated copper, but at the normalization of the free copper concentration in blood, to reverse the copper poisoning. This can be achieved safely and effectively with zinc therapy. Zinc induces metallothionein, a highly effective detoxification protein that binds copper. Oral zinc therapy leads to storage of metallothionein-bound copper in the mucosa of the gut and to the excretion of copper via the stools. New treatment guidelines advise against the use of chelating agents as initial treatment because they may aggravate copper intoxication and cause iatrogenic deterioration.
Anticopper therapy against cancer and diseases of inflammation and fibrosis 2006
http://www.sciencedirect.com/science/ar ... 4605035415
Anticopper drugs that have been developed to treat Wilson's disease, a disease of copper toxicity, include tetrathiomolybdate, zinc, penicillamine, and trientine. Lowering copper levels by a modest amount in non-Wilson's patients with tetrathiomolybdate inhibits angiogenesis, fibrosis and inflammation while avoiding clinical copper deficiency. Through this mechanism tetrathiomolybdate has proven effective in numerous animal models of cancer, retinopathy, fibrosis, and inflammation. Penicillamine has efficacy in rheumatoid arthritis and trientine has efficacy in diabetic neuropathy and diabetic heart disease. If clinical studies support the animal work, anticopper therapy holds promise for therapy of cancer, fibrotic disease and inflammatory and autoimmune diseases.
Zinc: A promising agent in dietary chemoprevention of cancer 2010
Proper intake of dietary nutrients is considered crucial for preventing the initiation of events leading to the development of carcinoma. Many dietary compounds have been considered to contribute in cancer prevention including zinc, which plays a pivotal role in host defense against the initiation and promotion of several malignancies. Zinc is an essential element that is integral to many proteins and transcription factors which regulate key cellular functions such as the response to oxidative stress, DNA replication, DNA damage repair, cell cycle progression, and apoptosis. Zinc has been ascribed roles in the metabolism and interaction of malignant cells, particularly in apoptosis. Zinc is involved in structural stabilization and activation of the p53 that appears to be an important component of the apoptotic process and also in activation of certain members of the caspase family of proteases. Zinc exerts a positive beneficial effect against chemically induced preneoplastic progression in rats and provides an effective dietary chemopreventive approach to disease in vulnerable section of population with family history of carcinoma. The present review provides an insight into the research conducted on animals as well as on human subjects for providing the concept that zinc deficiency is an important factor in the development and progression of malignancy and that zinc could be efficacious in the prevention and treatment of several cancers viz., colon, pancreas, oesophageal and head and neck. However, it needs further exploration with regard to other definitive bioassays including protein expression and documentation of specific molecular markers to establish the exact mechanism for zinc-mediated cancer chemoprevention. Preclinical trials need to investigate the genetic and epigenetic pathways of chemoprevention by zinc.
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