N-acetylcysteine amide, a novel cell-permeating thiol, restores cellular glutathione and protects human red blood cells from oxidative stress

Glutathione and the redox control system trypanothione/trypanothione reductase are involved in the protection of Leishmania spp. against nitrosothiol-induced cytotoxicity

“…It is recognised that similar molecular targets of NO are present in microorganisms and in mammalian cells (21,22) and, it has been demonstrated that glutathione protects several mammalian cells, including macrophages, against the oxidative stress induced by oxygen (23) and nitrogen-derived oxidants (11,24,25). Thus, the different intracellular glutathione levels may explain the large differences in susceptibility to SNAP among different species of Leishmania.…”

A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-κB and hypoxia-inducible factor-1α

“…Antioxidants which increase cellular cysteine levels, such as N-acetylcysteine (NAC), carbocysteine, and L-2-oxothiazolidine-4-carboxylic acid have been shown to exhibit anti-inflammatory effect and anti-hyperreactivity in animal models of asthma (Asti et al, 1995;Dworski, 2000;Blesa et al, 2002;Lee et al, 2004d). Recently, a novel, low-molecular weight thiol antioxidant, N-acetylcysteine amide (AD4), has been developed (Offen et al, 2004;Grinberg et al, 2005;Penugonda et al, 2005). In NAC, the carboxyl group is negatively charged at physiological pH, limiting the drug's ability to cross cell membranes.…”

“…In fact, AD4 has been shown to increase cellular levels of GSH either by providing the limiting substrate for GSH biosynthesis or reducing its oxidized form, glutathione disulfide (GSSG) in a thiol exchange reaction (Grinberg et al, 2005;Bartov et al, 2006). Moreover, studies have demonstrated that treatment with AD4 results in a remarkable restoration of intracellular thiols, a more effective protection against hemoglobin oxidation, and a substantial reduction of intracellular oxidation compared with NAC (Offen et al, 2004;Grinberg et al, 2005). However, there is no data on the influence and the molecular basis of AD4 on allergen-induced bronchial inflammation and airway hyperresponsiveness.…”

The Cardioprotective Role of Naca in the Prevention of Doxorubicin and Trastuzumab Mediated Cardiac Dysfunction

“…transfer its thiol group to oxidized glutathione (GSSG), thus regenerating GSH through redox chemistry. 105 The increased potency and bioavailability of NACA allows it to be administered at much lower dosages, thereby significantly decreasing the adverse effects that have been seen in NAC toxicity. There have been no reports of adverse effects of NACA in literature to date.…”

“…[104][105][106][107] Investigations into the anti-oxidant properties of NACA have demonstrated that the compound is able to scavenge free radicals, and protect red blood cells from OS through the prevention of ROS-induced activation of JNK, MAPK pathways, and matrix metalloproteinases. 105,106 In addition, another study exploring the anti-oxidant properties of NACA demonstrated that NACA (250mg/kg) was able to protect the blood brain barrier from OS in mice exposed to methamphetamine. 104 Studies have also been conducted in an in vitro model using embryonic rat cardiomyocytes exposed to DOX.…”