N-Acetylcysteine suppression of the proliferative index in the colon of patients with previous adenomatous colonic polyps

Estensen, Richard D.; Lévy, Michaël; Klopp, Steven J; Galbraith, Arthur R.; Mandel, Jack S.; Blomquist, Joyce A; Wattenberg, Lee W.

doi:10.1016/s0304-3835(99)00281-5

Cited by 49 publications

(30 citation statements)

References 10 publications

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“…The growth-promoting effects of ROS are related to redox-responsive signaling cascades, some of which have been discussed in section V. A placebocontrolled clinical study of patients with previous adenomatous colonic polyps, i.e., a group with an increased risk for colon cancer and increased proliferative index of colonic crypts, revealed a significant decrease in the proliferative index after treatment with N-acetylcysteine (170). Even normal cells often show increased proliferation and expression of growth-related genes if exposed to hydrogen peroxide or superoxide (81,118,123,419).…”

Section: Malignant Diseasesmentioning

confidence: 99%

Free Radicals in the Physiological Control of Cell Function

Dröge

2002

Physiological Reviews

8,447

5,836

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At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, however, nitric oxide (NO), superoxide anion, and related reactive oxygen species (ROS) play an important role as regulatory mediators in signaling processes. Many of the ROS-mediated responses actually protect the cells against oxidative stress and reestablish “redox homeostasis.” Higher organisms, however, have evolved the use of NO and ROS also as signaling molecules for other physiological functions. These include regulation of vascular tone, monitoring of oxygen tension in the control of ventilation and erythropoietin production, and signal transduction from membrane receptors in various physiological processes. NO and ROS are typically generated in these cases by tightly regulated enzymes such as NO synthase (NOS) and NAD(P)H oxidase isoforms, respectively. In a given signaling protein, oxidative attack induces either a loss of function, a gain of function, or a switch to a different function. Excessive amounts of ROS may arise either from excessive stimulation of NAD(P)H oxidases or from less well-regulated sources such as the mitochondrial electron-transport chain. In mitochondria, ROS are generated as undesirable side products of the oxidative energy metabolism. An excessive and/or sustained increase in ROS production has been implicated in the pathogenesis of cancer, diabetes mellitus, atherosclerosis, neurodegenerative diseases, rheumatoid arthritis, ischemia/reperfusion injury, obstructive sleep apnea, and other diseases. In addition, free radicals have been implicated in the mechanism of senescence. That the process of aging may result, at least in part, from radical-mediated oxidative damage was proposed more than 40 years ago by Harman ( J Gerontol 11: 298–300, 1956). There is growing evidence that aging involves, in addition, progressive changes in free radical-mediated regulatory processes that result in altered gene expression.

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Section: Malignant Diseasesmentioning

confidence: 99%

Free Radicals in the Physiological Control of Cell Function

Dröge

2002

Physiological Reviews

8,447

5,836

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“…41 Interestingly, NAC also protected the rat esophagus from caustic alkaline injury, which might be linked to the anti-inflammatory properties of this drug. 42 The demonstrated ability of NAC to modulate a broad spectrum of signal transduction pathways 15 and to decrease DNA synthesis, tumor cell proliferation and tumor promotion and progression [43][44][45][46][47] may have contributed to the observed lowering of severe preneoplastic lesions and tumors in the esophagus.…”

mentioning

confidence: 99%

Effects of N‐acetylcysteine in an esophageal carcinogenesis model in rats treated with diethylnitrosamine and diethyldithiocarbamate

Balansky¹,

Ganchev²,

D’Agostini³

et al. 2002

Intl Journal of Cancer

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Due to the increasing role of esophageal tumors in human cancer pathology, there is need for animal models evaluating the mechanisms of esophageal carcinogenesis and investigating protective factors toward this disease. Several N-nitrosamines have been shown to induce esophageal tumors in rats. We designed a study in BD 6 rats treated with N-diethylnitrosamine (DEN) according to a simple protocol involving weekly i.p. injections of this carcinogen for 8 consecutive weeks. This treatment resulted in a high incidence and multiplicity of liver tumors and in occurrence of preneoplastic lesions and papillomas in the esophagus. Intraperitoneal injections of diethyldithiocarbamate (DEDTC), 4 hr after each DEN injection, i.e., during the period of DEN metabolization, improved survival of rats and did not affect the liver tumor yield but doubled the incidence of esophageal tumors and enhanced 4.9؋ their multiplicity. Moreover, 15% of rats developed esophageal squamocellular carcinomas. The oral administration of the thiol N-acetyl-L-cysteine (NAC), a precursor and analogue of reduced glutathione, to rats treated with the DEN/DEDTC combination did not change the liver tumor yield but attenuated esophageal carcinogenesis by producing a significant shift of preneoplastic lesions to milder forms as well as a significant decrease of tumor multiplicity. Therefore, the DEN/DEDTC protocol appears to provide an interesting 2-organ model of N-nitrosamine-induced carcinogenesis in rats, in which NAC is moderately effective as an inhibitor. The mechanisms underlying enhancement of DENinduced esophageal carcinogenesis by DEDTC and the protective effects of NAC are discussed.

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“…Um volume de 350 µL (alça de 70 cm) da solução de referência ou amostra, contendo N-acetil-L-cisteína (N-acetil-CiSH), foi inserido na solução transportadora (H 2 O, 1,7 mL min -1 ) com ajuda do injetor-comutador. A solução injetada foi transportada até receber por confluência a solução Ce(SO 4 ) 2 2+ ) 2,5x10 -4 mol L -1 (R 2 ) a uma vazão de 0,7 mL min -1 . Como na bobina helicoidal B 1 há uma diminuição da concentração de Cério(IV) proporcionalmente ao aumento da concentração de N-acetil-L-cisteína (reação 1) origina-se, assim, um sinal transiente devido ao excesso de ferroína (reação 2), que é então monitorada espectrofometricamente em 500 nm.…”

Section: Sistema De Análise Por Injeção Em Fluxounclassified

“…Ademais, essa droga apresenta ação antioxidante e tem sido relatado que a mesma pode contribuir na prevenção de alguns tipos de câncer 1,2 . A atividade mucolítica 1 é devida a sua ação sobre as mucoproteínas e sua atividade é máxima em valores de pH entre 7 e 9.…”

Section: Introductionunclassified

Determinação indireta de N-acetil-L-cisteína por injeção em fluxo empregando Ce(IV) e ferroína

Vieira¹,

Fatibello‐Filho²

2005

Quím. Nova

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N-Acetylcysteine suppression of the proliferative index in the colon of patients with previous adenomatous colonic polyps

Cited by 49 publications

References 10 publications

Free Radicals in the Physiological Control of Cell Function

Free Radicals in the Physiological Control of Cell Function

Effects of N‐acetylcysteine in an esophageal carcinogenesis model in rats treated with diethylnitrosamine and diethyldithiocarbamate

Determinação indireta de N-acetil-L-cisteína por injeção em fluxo empregando Ce(IV) e ferroína

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