A -acetyl-cysteine

In rats receiving [ Cjbenzyl chloride in corn oil by gavage, the peak plasma level was reached after 30 min. The distribution half-life was 1.3 h, while the elimination half-life was 58.5 h. After 48 h, the higher concentrations were found in the stomach, gastric contents, ileum and duodenum, followed by liver, adrenal, bone marrow and blood. After 72 h, approximately 76% was excreted in urine and, in expired air, 7% as 002 and less than 1.3% as benzyl chloride or its metabolites. Urinary metabolites were identified as Y-benzyl-A-acetyl cysteine, benzx l alcohol and benzaldehyde (Saxena Abdel-Rahman, 1989). 

Scheme 67 Formation of the liver toxic metabolite A/-acetyl-4-benzochinonimine and its elimination and detoxification with gluthathione or (A/-acetyl)cysteine.

The chemical and toxicologic characterization of the electrophilic nature of the reactive acetaminophen metabolite has led to the development of effective antidotes—cysteamine and N-acetylcysteine. Administration of A-acetyl cysteine (the safer of the two) within 8-16 hours following acetaminophen overdosage has been shown to protect victims from fulminant hepatotoxicity and death (see Chapter 59 Management of the Poisoned Patient). 

Strategies to overcome the mucus barrier focus mainly on the use of mucolytic agents such as dithiothreitol (DTT) and A-acetyl cysteine (NAC). So far, however, results were rather disappointing in improving accessibility to the intestinal crypts for somatic gene therapy (Sandberg et. al. 1994). 

Another urinary metabolite of benzene is. V-phenyl-A-acetyl cysteine (PhAC) (Jongeneelen et al. 1987). 

A -Acetyl cysteine (amino acid, thiol) Aged garlic extract (= AGE) (thiols)... 

Exposure of SM to endothelial cells caused apoptosis and necrosis. Necrosis was accompanied by a significant depletion of intracellular ATP, while in apoptotic cells ATP remained at a level similar to healthy cells. Pretreatment with IV-acetyl cysteine all but eliminated the apoptotic features of cell death but did not prevent necrosis in response to SM. A-acetyl cysteine pretreatment prevented... 

A number of candidate molecules were evaluated against SM and meclorethamine toxicity using human bronchial-epithelial cell lines. The molecules tested were A-acetyl cysteine and WR-1065 (sulfhydryl containing... 

Estep JE, Lame MW,Jones AD, Segall HJ. A-Acetyl cysteine-conjugated pyrrolizidine alkaloids, monocrotaline and senecionine. Toxicol Lett 1990a 54 61-9. 

Most of the Cr+ foimd in nature is a result of domestic and industrial emissions. Interaction of -1-6 chromic oxide, dichromate, or chromate compoimds with organic compoimds can result in reduction to the comparatively less toxic trivalent form. Chromium compoimds interact synergistically or antagonistically with many chemicals. For example, potassium dichromate administered by subcutaneous injection potentiated the effects of mercuric chloride, citrinin, and hexachloro-1,3-butadiene on rat kidneys. Chromium effects were lessened by ascorbic acid and vitamin E, and A -acetyl cysteine was effective in increasing urinary excretion of chromium in rats. 

The open series above produces reactive oxygen species (ROS) on cancerous cells [85, 112, 113] but this is not universally the case as this is not observed with metastatic melanoma cells, yet the cytotoxic effect is still in evidence [114]. The case of melanoma may be an exceptional one as these very exposed cells possess a sophisticated antioxidant system [114]. It should be noted that the presence of antioxidants added into the medium, such as A-acetyl cysteine or vitamin E with... 

The use of AZA for IPF was first reported in an open-label trial by Winterbauer et al. (144). A subsequent double-blind, randomized trial demonstrated benefit versus placebo in approximately half of the patients treated (145). Demerits et al. demonstrated a higher response rate when AZA was given concomitantly with A-acetyl cysteine compared with AZA alone (146). AZA has also been used in the treatment of scleroderma-associated pulmonary fibrosis (147). Although not all investigators have reported benefit with the drug (148), the drug has also been useful in treating chronic pulmonary sarcoidosis (7). 

Although corticosteroid and immunosuppressive therapy can limit the lymphocytic inflammation, it does little to help airway dryness or inspisated mucus in bronchiectatic airways that can be occasionally helped with nebulized saline or A-acetyl cysteine. 

Table 3 Lack of Significant Effect of A -Acetyl Cysteine (NAQ on the Release of H-Catecholamines Elicited by H3fpoxia and High Extracellular K+...

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