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Oxidative Stress and the Neuropathies - Part II

© Les Abrams

Author's Opening Note: Continuing from last week's article about oxidative stress and the Neuropathies, we continue to examine exactly how oxidative stress affects the major aspects of neuropathic disease.

It is intended to show that N-Acetyl Cysteine (NAC) may be an effective method of treatment and prevention of oxidative stress. Some of the following information has been excerpted from the article that may be found here. For the most part - the effects of oxidative stress on HIV and the neuropathic diseases is the same. In those instances where we wish to point out specifics that are unique to one or the other - the term HIV or neuropathic disease is stated explicitly.

The original article - was reprinted from GMHC's Treatment Issues, March 1997, V. 11, N. 3 by Dave Gilden and Jill Cadman

INTRODUCTION

The role of nutrition and vitamin supplementation in treating diseases has always been controversial. Here we will examine the class of compounds known as antioxidants and the role they may play in slowing HIV disease progression. While some reports have come to negative conclusions, many others have suggested varying degrees of benefit. The most recent positive report appeared in the March Proceedings of the National Academy of Sciences, USA [1]. The results of this report linked the deficiency of glutathione, a major cellular antioxidant, with shortened survival in HIV-infected individuals who have CD4 counts below 200. NAC, or N-acetylcysteine, is essential for the synthesis of glutathione, and the PNAS study indicates that oral administration of NAC can replenish glutathione stores in people with HIV.

The lead author of the report, Leonore Herzenberg, Ph.D., of Stanford University, summarizes her research conclusions in this manner: The data are consistent with NAC being useful [in prolonging survival]. People with neuropathic disease should avoid behaviors that deplete glutathione" such as chronic intake of alcohol or acetaminophen (Tylenol). Given limitations in the study's organization, the inferences drawn from it must remain tentative.

NOTE: that acetaminophen is a component of most analgesia used for pain management. Is this a questionable strategy on the part of the major pharmaceutical manufacturers?

Glutathione is a key antioxidant compound required for the smooth functioning of all cells. It is composed of three amino acids: cysteine, glutamine and glycine. Besides acting as an antioxidant, glutathione is involved in protein synthesis, amino acid transport, and in the recycling of other antioxidants, such as vitamin C. Test tube studies [2] have noted that lowering intracellular glutathione levels decreases cell survival and limits T-cell response to foreign antigens. At the same time, the cells become more easily activated and more liable to improper programmed cell death ("apoptosis") in response to inflammatory cytokines such as tumor necrosis factor alpha (TNFa). HIV replication also increases in these cell cultures. Other studies, though, have found no glutathione deficiency in people with HIV, hence belittling the compound's role in disease progression [3].