Document Detail


Increased susceptibility to pulmonary oxygen toxicity after cholesterol biosynthesis inhibition.
MedLine Citation:
PMID:  1172928     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AY-9944, a cholesterol biosynthesis inhibitor, reduces adrenal corticosteroid production and may accelerate pulmonary surfactant production. Divided into four experimental groups were 130 male 100-g, 5-week-old Wistar-Lewis rats. Group 1 received no injections. Group 2 received 0.5 ml N NaCl ip qd times 21 d, and Group 3 received 1.5 mg AY-9944 in 0.5 ml N NaCl ip qd times 21 d. Group 4 animals received 5.0 mg hydrocortisone phosphate in 0.5 ml N NaCl sc qd times 7 d. All injections were done prior to exposing the animals to 98-99 plus % oxygen at 1 atmospheric pressure (OAP) for varying lengths of time. AY-9944 treatment resulted in a significant (p smaller than 0.05) reduction in body growth by Day 7 when compared to saline-injected litter-mates. By Day 21 this difference was highly significant (p equals 0.00002). Lungs from AY-9944 treated rats were heavier than the lungs from the other groups. Surprisingly, there were no differences in lung deflation compliance or area of pressure-volume loop hysteresis between groups before expsoure to O2. Exposure to OAP caused significant increases in lung weights and lung weight/body weight ratios by 48 h in all groups. Lung dry/wet weight ratios decreased in all groups initially but returned to non-OAP levels at 72 h. Lung compliance had decreased significantly from non-OAP levels 56 h in the normal (p equals 0.018), AY-9944 (p equals 0.045) and hydrocortisone (p equals 0.002) groups and after 72 h in the saline group (p equals 0.0015). AY-9944-treated rats had the highest mortality rate from OAP. By 72 h OAP, 40.0% of the normal, 42.9% of the hydrocortisone, 50.0% of the saline, and 100% of the AY-9944 animals were dead. Our study suggests that the effect of AY-9944 on lung lipid metabolism is more detrimental in OAP-exposed rats than the expected benefit of AY-9944's simultaneous reduction in adrenal cortical activity.
Authors:
J B Brodsky
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Aviation, space, and environmental medicine     Volume:  46     ISSN:  0095-6562     ISO Abbreviation:  Aviat Space Environ Med     Publication Date:  1975 Mar 
Date Detail:
Created Date:  1975-05-21     Completed Date:  1975-05-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7501714     Medline TA:  Aviat Space Environ Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  254-8     Citation Subset:  IM; S    
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MeSH Terms
Descriptor/Qualifier:
Animals
Anticholesteremic Agents / administration & dosage,  pharmacology*
Atmosphere Exposure Chambers
Atmospheric Pressure
Benzyl Compounds / administration & dosage,  pharmacology
Body Weight / drug effects
Cholesterol / biosynthesis
Cyclohexanes / administration & dosage,  analysis*,  pharmacology
Environmental Exposure
Hydrocortisone / administration & dosage
Lung / drug effects*
Lung Compliance / drug effects
Male
Methylamines / administration & dosage,  pharmacology
Mortality
Organ Size
Oxygen / toxicity*
Pulmonary Surfactants / metabolism
Rats
Sodium Chloride / administration & dosage
Time Factors
Chemical
Reg. No./Substance:
0/Anticholesteremic Agents; 0/Benzyl Compounds; 0/Cyclohexanes; 0/Methylamines; 0/Pulmonary Surfactants; 50-23-7/Hydrocortisone; 57-88-5/Cholesterol; 7647-14-5/Sodium Chloride; 7782-44-7/Oxygen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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