Zinc's protection

[Guest guest]

Hello Group,

Here is a useful article and does touch upon the blood brain barrier that Lance

was asking about.

Du Pre

Website: http://www.angelfire.com/jazz/isaiah40soaringeagle/index.html

" By words the mind is winged. " Aristophanes

The Antioxidant Function of Dietary Zinc and Protection Against Neural

Disorders

Mark A. Levy, Ph.D.

OSU Research Associate

Tammy M. Bray, Ph.D.

Professor of Nutrition and Food Management

LPI Senior Scientist

Zinc, a ubiquitous trace element found throughout the plant and animal

kingdoms, was first demonstrated to be an essential component of the human

diet in the 1960s when it was found to reverse delayed sexual development

and arrested growth. Since then, numerous syndromes associated with zinc

deficiency, including immune and nervous system abnormalities, have been

described in infants, adolescents, and the elderly.

Although zinc is a component of more than 70 different enzymes that function

in almost every aspect of cellular metabolism, researchers have been unable

to identify a specific biochemical function that can account for the many

different signs and symptoms of zinc deficiency. Zinc's function as an

antioxidant was first proposed in 1990, based largely upon in vitro evidence

that illuminated two distinct mechanisms. The first is the protection of

proteins and enzymes against free radical attack, or oxidation. Free

radicals are very unstable molecules that react quickly and deleteriously

with other substances, damaging their normal functions. The zinc molecule in

zinc-containing enzymes was found to act as an antioxidant and protect

specific regions of the enzyme from free radical attack, thus preserving its

stability and activity. Dr. ph Beckman of LPI has been investigating the

role of zinc in Lou Gehrig's disease, also known as amyotrophic lateral

sclerosis (ALS). He found that when superoxide dismutase, an endogenous

antioxidant enzyme, loses its zinc atom, it becomes neurotoxic (see the

Spring/Summer 2001 LPI Newsletter). The second mechanism by which zinc

functions as an antioxidant is through the prevention of free radical

formation by other metals, such as iron and copper. Unlike highly reactive

iron and copper, zinc does not readily undergo oxidation and reduction, or

redox, reactions. In redox reactions electrons are transferred to and from

different compounds, sometimes resulting in the generation of free radicals.

When zinc, instead of iron or copper, is incorporated into proteins, free

radical generating reactions that may otherwise occur are inhibited.

Although the antioxidant properties of zinc were first demonstrated in

vitro, there is also clear evidence that zinc functions as an antioxidant in

the body. One area of growing interest is the role of zinc as an antioxidant

in the central nervous system (CNS), particularly the brain. Compared to

other soft tissues, the human brain contains significant amounts of zinc.

Among the essential trace elements, zinc is second only to iron in total

concentration in the brain. Zinc deficiency has been proposed to lead to

nervous system disorders, including mental disturbances, loss of sensory

acuity, and impaired cognitive and psychological function. Notably,

oxidative stress is associated with the development and progression of

several different neuropathologies, including Alzheimer's disease, ALS, and

Parkinson's disease.

We recently examined the role of zinc in maintaining the integrity of the

blood brain barrier (BBB), which is the highly specialized blood vessel

system of the CNS that serves to protect the brain by excluding toxic agents

and other foreign compounds. Alterations or dysfunction of the BBB have been

observed in many brain disorders. Free radicals may play an important role

in damaging the BBB because it is especially sensitive to oxidative damage.

This vulnerability may be due to the high polyunsaturated fatty acid content

of the BBB membrane-fatty acids that are very susceptible to free radical

attack-as well as the relatively low antioxidant capacity of the BBB.

Oxidation of the membrane drastically compromises its barrier properties and

may lead to subsequent brain tissue damage, resulting in a host of

pathologies.

Our investigations have focused on the antioxidant function of zinc that may

protect the BBB against oxidative damage. Using magnetic resonance imaging,

or MRI, we have demonstrated that zinc deficiency in rats dramatically

increases the permeability, or leakiness, of the BBB. Additionally, we have

observed that when zinc deficiency is accompanied by oxidative stress, as

might occur during a bacterial or viral infection, BBB permeability

increases dramatically. These observations have led us to hypothesize that

under normal conditions, zinc protects the BBB against oxidative stress

through its antioxidant properties and in so doing, helps to maintain

homeostasis within the brain and prevent the development of neurological

disorders.

In our initial work we examined the consequences of the loss of BBB

integrity during zinc deficiency. First, we noted significantly increased

water content, or edema, of the brain as a result of zinc deficiency.

Second, we observed increased protein oxidation within the brain. And third,

we documented significant changes in brain energy metabolism. These

observations led us to propose that these events may be pivotal in the

development and pathogenesis of many brain disorders, and our laboratory

will continue to define the important roles of zinc in disease prevention.