Veggies Offset Inflammatory Response
November 17, 2009
Scientists at
the Univ. of Pennsylvania School of Medicine discovered that a dietary
antioxidant found in such vegetables as broccoli and cauliflower protects cells
from damage caused by chemicals generated during the body�s inflammatory
response to infection and injury. The finding has implications for such
inflammation-based disorders as cystic fibrosis (CF), diabetes, heart disease,
and neurodegeneration.
Through cell-culture studies and a synthesis of
known antioxidant biochemistry, Zhe Lu, professor of physiology, Yanping Xu ,
senior research investigator, and Szilvia Sz�p , postdoctoral researcher, showed
that the antioxidant thiocyanate normally existing in the body protects lung
cells from injuries caused by accumulations of hydrogen peroxide and
hypochlorite, the active ingredient in household bleach. These potentially
harmful chemicals are made by the body as a reaction to infection and injury.
In addition, thiocyanate also protects cells from hypochlorite produced
in reactions involving MPO, an enzyme released from germ-fighting white blood
cells during inflammation. They published their findings in the Proceedings of
the National Academy of Sciences.
�Lu�s work throws new light on how the
genetic defect underlying CF leads to the lung illnesses that are the leading
cause of death,� says Bert Shapiro, who oversees membrane structure grants at
the NIH�s National Institute of General Medical Sciences (NIGMS). �His team�s
findings suggest that the lungs of people with the disease are more susceptible
to the damaging effects of cellular oxidants. While the idea is tantalizing and
creative, further testing is needed to confirm it.�
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
