Role of Cysteine and Glutathione in HIV Infection and Cancer Cachexia: Therapeutic Intervention with N-Acetylcysteine

Abstract

Publisher Summary Massive loss of skeletal muscle mass (cachexia) is sign of HIV infection, sepsis, and trauma, and a cause of death among cancer patients. In HIV infection, the immunological dysfunction develops progressively into a severe condition called acquired immunodeficiency syndrome. Increasing evidence suggests that an abnormal cysteine and glutathione metabolism plays a decisive role in the development of catabolic conditions and associated immunological dysfunctions. This chapter gives a conceptual overview; the chances for a therapeutic intervention with cysteine derivatives such as N-acetylcysteine (NAC) and the methodological aspects. The agenda is to identify abnormal biochemical patterns in different catabolic diseases and conditions, abnormal biochemical parameters that are significantly correlated with mortality, disease progression, and weight loss, to prove cause-and-effect relationships by experimental intervention, to develop and optimize interventive strategies that may be suitable for clinical therapy, and to test new therapeutic strategies in clinical trials. Discussed are the elevated venous plasma glutamate levels as universal marker for catabolic and precatabolic conditions—evidences for an impairment of muscular membrane transport activities, abnormal cysteine catabolism and glutathione level in skeletal muscle tissue, and the pathological significance of decreased membrane transport activity and elevated venous plasma glutamate levels. There is discussion on “Push” and “Pull” mechanisms in catabolic and precatabolic processes, decreased plasma cystine levels and evidence for “Push” and “Pull” mechanisms in sepsis, HIV Infection, and other malignant diseases, abnormally low plasma cystine and glutamine levels in patients with chronic fatigue syndrome (CFS), and the hypothetical mechanism of the “pull” condition—evidence for an abnormal cysteine and glutathione metabolism in liver. Noted are the immunological implications—cysteine deficiency and immunological dysfunction, abnormal glutathione levels in HIV Infection, and redox regulation by glutathione and glutathione disulfide. Also, there are details on the therapeutic intervention with a cysteine derivative: effects of long-term treatment with N-acetylcysteine.