N-Acetylcysteines

Mucolytic and anti-oxidant drugs include ambroxol, N-acetylcysteine, carbocysteine and iodinated glycerol. These drugs have no proven effect on lung function. At... 

Aromatic diazonium salts react easily in neutral aqueous solution with thiols such as N-acetylcysteine, forming compounds of the type Ar — N2 —S —CH2CH(NHAc) COOH. Nifontov et al. (1990) suggested that such compounds, e.g., that of 5-diazo-imidazole-4-carboxylate, function as a form of transport depot for cytotoxic diazo-carboxylate in the human body. 

TSAI J-C, JAIN M, HSIEH C-M, LEE W-S, YOSHIZUMI M, PATTERSON C, PERRELLA M A, COOKE C, WANG H, HABER E, scHLEGEL R, and LEE M E (1996) Induction of apoptosis by pyrrolidinedithiocarbamate and N-acetylcysteine in vascular smooth muscle cells Journal Biological Chemistry 271, 3667-70. 

Like sulforaphane, however, PEITC-NAC (N-acetylcysteine) conjugate appears to block in Gl. Studies by Lund et al. show that in the case of the colorectal cell line HT29, which lacks wild type p53, treatment with AITC causes the cells to detach from the substratum but, at least in the short-term, they do not then enter apoptosis . Where it does occur, induction of apoptosis by isothiocyanate appears to be a p53-dependent process. However, this statement must also be qualified, because the effect appears to depend on which metabolite is considered. For example, sulforaphane does appear to be able to induce apoptosis in HT29 cells, which express a mutated form of the protein. 

CHUNG F L, KELLOFF G, STEELE V, PITTMAN B, ZANG E, JIAO D, RIGOTTY J, CHOI C I and RiVENSON A (1996) Chemopreventive efficacy of arylalkyl isothrocyanates and N-acetylcysteine for lung tumorigenesis in Fischer rats . Cancer Res, 56 772-8. 

CHIAO J W, CHUNG F, KRZEMINSKI J, AMIN S, ARSHAD R, AHMED, T aud CONAWAY C C (2000) Modulation of growth of human prostate cancer cells hy the N- acetylcysteine conjugate of pheuethyl isothiocyanate , Int J Oncol, 16 1215-9. 

When N-acetylcysteine and thiomalate were studied in a mixed ligand system, the respective activation entropies were found to be AS = —141 and —151J mol ... 

In bronchitics, there have been reports of elevated serum-conjugated dienes, hydroperoxides and aldehydes, and a claim of clinical eflicacy as well as normalization of these parameters after vitamin E therapy (Kleiner et al., 1990). However, these patients were given combined therapy including steroids and thus the effect of vitamin E alone cannot be assessed. N-Acetylcysteine administered to chronic bronchitics increased plasma cysteine from a below-normal baseline but it has not been shown that this intervention had any effect on the disease process, the dosing being of short duration, nor were there short-term effects of the release of ROS from blood neutrophils (reviewed by MacNee et al., 1991). A... 

In a percussive brain injury model in cats, N-acetylcysteine (NAG) preserved normal hyperventilation when administered either prior to or 30 min post-insult (Ellis etal., 1991), NAG was also found to be active in a model of acute immunological alveolitis in the rat in... 

Ellis, E.F., Dodson, L.Y. and Police, R.J. (1991). Restoration of cerebrovascular responsiveness to hyperventilation by the oxygen scavenger N-acetylcysteine following experimental brain injury. J. Neurosurg. 75, 774-779. 

Sala, R., Moriggi, E., Corvasce, G. and Morelli, D. (1993). Protection by N-acetylcysteine a iinst pulmonary endothelial cell damage induced by oxidant injury. Eur. Respir. J. 6, 440-446. 

NAAb Natural autoantibody NAb Natural antibody NAC N-acetylcysteine NADH Reduced nicotinamide adenine dinucleotide NADP Nicotinamide adenine diphosphate... 

N-acetylcysteine has antioxidant and mucolytic activity, which makes it a promising agent for COPD treatment, but clinical trials have produced conflicting results. One of the largest trials found N-acetylcysteine to be ineffective at reducing the decline in lung function and preventing exacerbations.29 Routine use cannot be recommended at this time. 

Dornase alfa (Pulmozyme ) is a recombinant human (rh) DNase that selectively cleaves extracellular deoxyribonucleic acid (DNA). This DNA is released during neutrophil degradation and contributes to the high viscosity of CF sputum. Nebulization of dornase alfa 2.5 mg once or twice daily improves daily pulmonary symptoms and function, reduces pulmonary exacerbations, and improves quality of life.16 N-acetylcysteine and hypertonic saline are other mucolytic agents that are occasionally used however, they are not preferred agents due to a greater incidence of bronchospasm and unpleasant odor and taste.5... 

Disorders of glutathione Defective synthesis of glutathione, the major intracellular antioxidant Spinocerebellar degeneration, mental retardation, cataracts, hemolysis. Severe acidosis in some cases N-acetylcysteine (variable response)... 

Humidification of inspired air may promote the hydration (liquefaction) of tenacious secretions, allowing for more effective sputum production. The use of mucolytic aerosols (e.g., N-acetylcysteine deoxyribonuclease) is of questionable therapeutic value. Mucolytics may have the greatest benefit... 

No information is available on the adverse health effects of hexachloroethane in humans. Animal studies revealed that hexachloroethane primarily causes liver and kidney toxicity. Effects on the nervous system and lungs have also been reported. The mechanism by which these effects are mediated is not well characterized. Reductive metabolism by cytochrome P-450 and production of a free radical intermediate have been suggested as factors in hexachloroethane-induced hepatotoxicity (Nastainczyk et al. 1982a Thompson et al. 1984 Town and Leibman 1984). Accordingly, one possible approach may be to reduce free radical injury. To that end, oral administration of N-acetylcysteine can be used as a means of reducing free radical injury. Also, oral administration of vitamin E and vitamin C may be of value since they are free radical scavengers. 

However, a few thiols (cysteine, N-acetylcysteine and thiosalicylic acid) also react with organic nitrates to release NO by another process that is difficult to discern. It could be that the nitrite reacts with a thiol to give an S-nitrosothiol, a ready source of NO, but nitrosation is unlikely to occur at biological pHs. Another possible route to NO involves formation of a thionitrate by trans-esterification [59] (Eq. (12)). This species could then decompose to give NO via an intermediate sulfenyl compound [60] (Eq. (13)). 

Attempts to counteract tolerance development include the use of thiols such as N-acetylcysteine, antioxidants such as vitamin C and vitamin E, and angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists. Other approaches to decreasing the development of tolerance include intermittent therapy... 

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