Lung Protection by a Thiol-Containing Antioxidant: N-Acetylcysteine

Abstract

N-acetylcysteine (NAC) is a thiol-containing compound which nonenzymatically interacts and detoxifies reactive electrophiles and free radicals. NAC was shown to effectively protect human bronchial fibroblasts against the toxic effects of tobacco smoke condensates and the isolated perfused lung against the glutathione (GSH)-depleting effect of tobacco smoke. NAC was also shown to reduce the reactive oxygen intermediate hydrogen peroxide (H₂O₂) and protect against the toxic effects of H₂O₂. In vivo studies, however, demonstrated that NAC when administered orally has very low bioavaibility due to rapid metabolism to GSH among other metabolites. Thus, even though NAC is very effective in protecting cells of different origins from the toxicity of reactive components in tobacco smoke and reactive oxygen species, a direct scavenging effect by NAC in vivo, particularly when administered orally, does not seem likely. The bioavailability of NAC itself is very low when given this route. A more relevant mechanism in vivo for any protective effect NAC may exert against toxic species may be due to NAC acting as a precursor of GSH and facilitating its biosynthesis. GSH will then serve as the protective agent and detoxify reactive species both enzymatically and nonenzymatically

Pathophysiologic Mechanisms of Three Pulmonary Edemagenic Compounds: The Role of Toxic Oxygen Species.

“…The drugs chosen for study in these experiments are believed to interfere, directly or indirectly, with generation of toxic oxygen species or aid in the disposition of toxic radicals. N-acetylcysteine is thought to contribute to intracellular replenishment of glutathione, which subsequently acts as a sacrificial oxidant to conjugate active oxygen species (Moldeus et al, 1986). Pentigetide is thought to moderate immune inflammatory reactions (Hamburger, 1975) with their associated inflammatory oxygen radical production.…”

N-acetilcisteína - ação antioxidante e utilização na clínica de pequenos animais

“…Sua indicação terapêutica, por muitos anos, ficou restrita à ação mucolítica e expectorante, bem como ao tratamento da intoxicação por paracetamol, tanto na Medicina quanto na Medicina Veterinária (Wilcke, 1984;Moldeus et al, 1986;Plumb, 2005). A ação antioxidante da Nacetilcisteína deve-se à sua utilização como substrato para a síntese de glutationa peroxidase (cedendo a cisteína), um potente antioxidante, e ao átomo de hidrogênio presente no grupo tiol ou sulfidrila (-SH), que atua como um elétron na neutralização de radicais livres (Brunet et al,1995;Di Mari et al, 1997;Didoné et al, 2002).…”

“…A N-acetilcisteína é um aminoácido que, por muito tempo, foi utilizado como mucolítico e antídoto na intoxicação por paracetamol (Wilcke, 1984;Moldeus et al, 1986;Plumb, 2005). Atualmente, sua função antioxidante tem sido destacada em estudos acerca de substâncias reativas do metabolismo do oxigênio e radicais livres, como o peróxido de hidrogênio e o superóxido (Didoné et al, 2002;Miranda et al, 2004).…”

Neuron differentiation and neuritogenesis stimulated by N-acetylcysteine (NAC)

“…N-acetylcysteine (NAC), a precursor of glutathione, is a potent antioxidant and free radical scavenger that effectively reduces free radical species and other oxidants [1] . The neuroprotective effect of NAC has been demonstrated in ischemia and ischemia/reperfusion models [2][3][4][5] , and in traumatic injury of the nervous system [6] .…”