Protection by cysteine esters against chemically induced pulmonary oedema

Lailey, Alison F; Hill, Lawrence J.; Lawston, I. W.; Stanton, D.; Upshall, D. G.

doi:10.1016/0006-2952(91)90391-h

Cited by 66 publications

(47 citation statements)

References 19 publications

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“…Our finding that repeat oral administration of NAC to rats does not increase lung GSH content is consistent with findings of Lailey (1997) and Lailey et al (1991). However, lung cysteine levels were found to be increased 150% following intraperitoneal injection of NAC (Lailey et al, 1991).…”

Section: Discussionsupporting

confidence: 90%

Impact of 30-Day Oral Dosing with N-acetyl-l-cysteine on Sprague-Dawley Rat Physiology

et al. 2004

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The public reportina burden for this collection of information is estimated to average 1 hour per response, including the lime for reviewing instnjotlons. ^^.^/^^'"a existing data sou^^^^^ gathering and malnteining the data needed, and completing and reviewing the collection of lnfom,ation Serjd comments regarding this Ijurden estimate or any other asped of ^|^*='™ <>' infonnation including suggestions for reducing this burden to Washington Headquarteis Services. Directorate for infomiation , 1215 Jefferson Dav^s High™y;suite 12IH Arlington VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for falling to comply with a collection of Information if it does not display a currently valid 0MB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT TJ-PE Final REPORT DATE (DD-MM-YYYY) 07-13-2004 TITLE AND SUBTITLE Impact SPONSOR/MONITOR'S ACRONYM(S) SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION/AVAILABILITY STATEMENTApproved for public release; distribution is unlimited. SUPPLEMENTARY NOTES 242 ABSTRACT (Maximum 200 words)A number of studies have demonstrated a protective effect associated with N-acetyl-L-cysteine (NAC) against toxic chemical exposure. However, the impact of long-term oral dosing on tissue pathology has not been detennlned. In this study, we assessed the impact of long-term oral NAC administration on organ histopathology and tissue glutathione (GSH) and total glutathione-Stransferase (GST) activity levels in Sprague-Dawley (SD) rats. Groups of 20 SD rats (10 male, 10 female), 8 weeks of age, were dosed daily by oral gavage with deionized H2O (negative controls) or NAC solution at a rate of 600 or 1,200 mg/kg/d for 30 days. Animals were euthanized 6 hours after treatment on study Day 30. There were no significant differences in final body weights or weekly average weight gain between treatment groups. Serum alanine aminotransferase (ALT) activities were significantly elevated (p^O.05) in NAC-treated animals compared to controls when measured on study Day 30. Histopathologic evaluation of the liver, stomach, small intestine, liver, kidneys, spleen, thymus, and lungs revealed no lesions associated with NAC administration. When measured on study Day 30, total GST activity for kidney and skin from NAC-treated animals were increased 39-131% as compared to controls. Tissue GSH concentrations from NAC-treated animals were increased 24-81% as compared with negative controls. -H=wthePsfadies-afe-Fieede€l-te-d6teFmiB6-i^4he-observed4ocreaseJn-tissue GSH concentration and GST activity provide a degree of chemoprotection against dernial and systemic chemical toxicants. SUBJECT TERMS Disclaimer:This work was supported by the U.S. Navy Office of Naval Research Work Unit #60263. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the U.S. Government. This article is approved for pubhc release, di...

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Section: Discussionsupporting

confidence: 90%

Impact of 30-Day Oral Dosing with N-acetyl-l-cysteine on Sprague-Dawley Rat Physiology

et al. 2004

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“…NPSH were measured by a modified Ellman's assay [13]. In brief, the cells were rinsed with PBS, scraped into 1 mL of ice-cold 0.6% sulphosalicylic acid (SSA), treated with Triton X-100 at 0.01% for 1 h on ice, spun and the supernatant assayed.…”

Section: Treatmentsmentioning

confidence: 99%

Hydrogen peroxide-induced epithelial injury: the protective role of intracellular nonprotein thiols (NPSH)

Mulier¹,

Rahman²,

Watchorn³

et al. 1998

Eur Respir J

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Injury to the alveolar region is a hallmark of the adult respiratory distress syndrome (ARDS) whereas injury to the epithelium of the conducting airways is a characteristic of asthma. Reactive oxygen species have been implicated as mediators of lung injury in both of these conditions. We have investigated the relationship between intracellular nonprotein thiols (NPSH), and the release of the cytosolic enzyme lactate dehydrogenase (LDH), as an index of cell injury, following treatment of the human alveolar type II-like epithelial cell line (A549 cells) or the human bronchial epithelial cell line (16HBE140-) with hydrogen peroxide (H2O2). We have also assessed the protective effects of pre-incubation of both of these cells lines with H2O2 or enhancement of intracellular NPSH against H2O2-induced cell injury. Exposure of A549 and 16HBE140- cells to H2O2 (0.1 mM and 1 mM respectively for 16 h) produced the release of 40% of the total cellular LDH. H2O2 exposure produced an initial dose-dependent decrease in NPSH in A549 cells, with a subsequent increase to above control values. 16HBE140- cells also showed a dose-dependent decrease in NPSH following exposure to H2O2. Pretreatment of A549 cells with 0.1 mM H2O2 followed by subsequent exposure to H2O2 did not protect against H2O2-induced LDH release in this epithelial cell line. Pre-incubation with 2 mM N-acetylcysteine (NAC) increased NPSH but not intracellular reduced glutathione and resulted in total inhibition of H2O2-induced LDH release in both cell types. Pretreatment with reduced glutathione protected both cell types against the injurious effects of H2O2, whereas glutathione monethyl ester (GSHMEE) only partially protected A549 cells and had no effect in 16HBE140- cells. Intracellular cysteine levels were increased in both cell lines following NAC exposure but not sufficiently to account for the increase in NPSH levels. These observations raise the possibility that a critical concentration of nonprotein thiols may be necessary to protect pulmonary epithelial cells against hydrogen peroxide-induced injury.

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“…Yourick et al 4 demonstrated some protection against HD-induced microvesication using NIA as a treatment in hairless guinea pigs, but this compound has not been tested against an inhalation challenge. Lailey et al 5 used NAC as an effective treatment against lethality due to perfluoroisobutylene inhalation in rats. Wilde and Upshall 6 found NAC ineffective against HD poisoning in the in vitro cultured lung slice model.…”

Section: Introductionmentioning

confidence: 99%