Cysteine/Glutathione Deficiency: A Significant and Treatable Corollary of Disease

Ghezzi, Pietro; Lemley, Kevin V.; Andrus, James P.; De Rosa, Stephen C.; Holmgren, Arne; Jones, Dean; Jahoor, Farook; Kopke, Richard; Cotgreave, Ian; Bottiglieri, Teodoro; Kaplowitz, Neil; Nakamura, Hajime; Staal, Frank; Ela, Stephen W.; Atkuri, Kondala R.; Tirouvanziam, Rabindra; Heydari, Kartoosh; Sahaf, Bita; Zolopa, Andrew; Frye, Richard Eugene; Mantovani, John J.; Herzenberg, Leonard A.; Herzenberg, Leonore A.

Glutathione (GSH) deficiency may play a pivotal role in a variety of apparently unrelated clinical conditions and diseases. Orally administered N-acetylcysteine (NAC), which replenishes the cysteine required for GSH synthesis, has been tested in a large number of randomized placebo-controlled trials involving these diseases and conditions. This chapter focused on developing a base of evidence suggesting that NAC administration improves disease by increasing cysteine and/or GSH in a variety of diseases, thereby implying a significant role for GSH deficiency in the clinical basis of many diseases. To develop this base of evidence, we systematically selected studies which considered the hypothesis that the therapeutic efficacy for NAC is an indication that cysteine and/or GSH deficiency is a pathophysiological part of the diseases studied. In this manner we focus this chapter on explaining the biological mechanisms of NAC therapy in a wide variety of disorders and demonstrate its ubiquitous role in improving disease that involves disrupted GSH and/or cysteine metabolism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/978-981-10-5311-5_20) contains supplementary material, which is available to authorized users.