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The research team demonstrated that in three additional cell types used to extend their ideas to other inflammation-related conditions?-cardiovascular disease, neurodegeneration, and diabetes-?thiocyanate at blood concentrations of at least 100 micromolar greatly reduces the toxicity of MPO in cells, including those lining blood vessels. Humans naturally derive thiocyanate from some vegetables and blood levels of thiocyanate in the general population vary from 10 to 140 micromolar.

This comparison raises the possibility that without an adequate dietary supply of thiocyanate, hypochlorite produced by the body during inflammation would cause additional collateral damage to cells, thus worsening inflammatory diseases, and predisposing humans to diseases linked to MPO activity, including atherosclerosis.

For over a decade Lu and colleagues have been exploring the inner workings of ion channels and how this knowledge relates to the pathology of such diseases as CF. The CF disease originates from mutations in the CF transmembrane conductance regulator (CFTR) protein, an ion channel protein in the cell membrane commonly thought to transport mainly chloride ions. It has, however, remained a mystery why a defect in a chloride-transporting channel leads to cystic fibrosis, a disease with exaggerated inflammation in both the lungs and the digestive system.

Lung injuries inflicted by excessive inflammation and recurring infection cause about ninety percent of CF patients? symptoms and mortality. Although known as a chloride channel, CFTR also conducts thiocyanate ions, important because, in several ways, they can limit potentially harmful accumulations of hydrogen peroxide and hypochlorite, chemicals produced by the body to fight germs.

In CF patients, there is also a high incidence of diabetes, partly caused by damage to the pancreas. Type 2 diabetes is also associated with higher levels of MPO in the blood. The researchers found that the MPO-caused injuries to pancreas cells and endothelial cells used in their experiments can be greatly reduced by as little as 100 micromolar thiocyanate. Their finding raises the possibility that MPO, in the absence of adequate thiocyanate, contributes to diabetes.

In the cell-based experiments, thiocyanate at concentrations below 100 micromolar did not eliminate hypochlorite accumulation and did not fully protect against MPO toxicity. Conceivably, inadequate thiocyanate levels would aggravate MPO-produced injuries in patients suffering from inflammatory diseases, surmise the authors.

The research team found that MPO-caused injuries to nerve cells, as well as to blood vessel-lining endothelial cells, can be greatly reduced by 100 micromolar thiocyanate.

Source: Univ. of Pennsylvania