Glycosaminoglycan synthesis in amiodarone-induced pulmonary fibrosis
Glycosaminoglycans (GAG) have previously been demonstrated to be synthesized in greater than normal amounts following a single intratracheal insufflation of bleomycin in hamsters. This suggests that GAG may play a role in the propagation of pulmonary fibrotic reactions. To further test this hypothesis, GAG synthesis was studied in a new hamster model of interstitial lung injury, induced by the cardiac drug, aminodarone. Animals received a single intratracheal instillation of 1.25 mg aminodarone. At 4, 9, and 21 days post-insufflation, the animals were sacrificed, their lungs removed, and 1 mm fragments placed in explant culture for 6 hours at 37/sup 0/C in the presence of /sup 35/S-sulfate. The labeled GAG were isolated and measured for /sup 35/S incorporation. The author then isolated the hexosamine portions of the respective GAGs, Heparan Sulfate (HEP S), Chondroitin-6-Sulfate (Ch-6-S) and Chondroitin-4-Sulfate and Dermatan Sulfate (CH-4-S and DS) using the enzyme ABC and paper chromatography. They also studied the GAG content and distribution in hamster lung fibroblasts incorporated with /sup 35/S for 48 hours and subjected to either 0, 0.01 mg, 0.1 mg, or 1 mg of aminodarone. GAG synthesis is increased at an early stage following the induction of lung injury by aminodarone and remains elevated for a 3 week period. The change in GAG distribution boards elevated CH-4-S and DS may be characteristic of interstitial diseases in general. The GAGs that are synthesized by fibroblasts may be responsible for the increased CH-4-S and DS synthesis.
- Research Organization:
- Columbia Univ., New York (USA)
- OSTI ID:
- 6527301
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
FIBROSIS
PATHOGENESIS
GLUCOPROTEINS
BIOSYNTHESIS
SULFUR 35
UPTAKE
CARDIOVASCULAR AGENTS
DOSE-RESPONSE RELATIONSHIPS
HAMSTERS
LUNGS
SULFATES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARBOHYDRATES
DAYS LIVING RADIOISOTOPES
DRUGS
EVEN-ODD NUCLEI
ISOTOPES
LIGHT NUCLEI
MAMMALS
NUCLEI
ORGANIC COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
PATHOLOGICAL CHANGES
PROTEINS
RADIOISOTOPES
RESPIRATORY SYSTEM
RODENTS
SACCHARIDES
SULFUR COMPOUNDS
SULFUR ISOTOPES
SYNTHESIS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques