Glutathione, Toxins and Free Radicals

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Living organisms have developed a complex system of defense systems

against atmospheric reactive oxygen species (ROS), reactive nitrogen

and nitrogen doxide species (RNS) (ie ozone) and Reactive Chlorine

(RCS). Epithelial surfaces which include the respiratory tract (also

gastrointestinal tract) contain an antioxidant network that provides

defense against environmental stresses caused by reactive species in

order to reduce their ability to injure underlying cells. The

antioxidant network is an extremely important part of the protective

system against oxidizing environments. The products of these reactive

species act as secondary messengers to induce proinflammatory

chemokines and cytokines. Incidentally, antioxidants are the first

line of defense against inhaled oxidants and bronchial tract fluids

contain glutathione GSH) in higher levels. It has been found that GSH

levels are reduced in many respiratory diseases and that high levels

of GSH and N-Acetyl-L-cysteine prevents the peroxidative stress when

administered for septic shock. For this reason, further strategies to

increase airway surface " antioxidants " to reduce cell damage in the

airways by reactive species from toxins is clearly warranted.

Free radical and other reactive species activity have been implicated

in the injurious effects of toxins in a number of ways; 1) by being a

reactive species itself 2) the toxins metabolize to a reactive

species 3) the reactive species goes through redox and then

reoxidized 4) the toxin interferes with antioxidant defenses. Many

toxins are metabolized by conjugation with GSH, and a large dose of

toxin will deplete GSH and lead to secondary oxidative damage by

failure to remove free radicals. The liver supplies GSH to other body

tissues so damage to the liver can cause levels of GSH to fall

elsewhere. 5) the toxin stimulates endogenous generation of reactive

species by affecting mitochondrial action and injures cells by

interfering with ATP production. 6) toxins may combine with other

molecules to create new antigens. 7) a combination of any of the

above….

As you can see from the above, free radical reactions are involved in

the actions of toxin activity. However, published reports do not

often address whether reactive species cause the toxicity or reactive

species formation is a later stage in the process of cell injury. (1)

Source:

1. Halliwell, Barry and Gutteridge, Free Radical in Biology and

Medicine, Pgs 440-442. Oxford University Press, 2007.

2. Fuchs, Jurgen and Lester Packer, Editors. Environmental Stressors

in Health and Disease. Pg 227-229. 2001.