Benoxaprofen stimulates proteoglycan synthesis in normal canine knee cartilage in vitro
Several nonsteroidal antiinflammatory drugs which are cyclooxygenase inhibitors (e.g., salicylates, fenoprofen, ibuprofen) have been shown to suppress proteoglycan synthesis by normal joint cartilage in vitro. We examined the effect of benoxaprofen, a long-acting proprionic acid derivative which inhibits lipoxygenase in addition to causing moderate cyclooxygenase inhibition. When added to the culture medium in concentrations comparable with those obtainable in serum of patients treated with the drug (e.g., 10 and 50 micrograms/ml), benoxaprofen increased proteoglycan synthesis in slices of normal canine knee cartilage to 126% and 135%, respectively, of control levels. These concentrations of the drug augmented net protein synthesis to 154% and 123%, respectively, of control levels. Incorporation of /sup 3/H glucosamine into 9-aminoacridine precipitable material was increased by benoxaprofen, showing that it stimulates net proteoglycan synthesis, and not merely sulfation. At concentrations of either 10 or 50 micrograms/ml, the drug had no effect on proteoglycan catabolism or on the ability of proteoglycans to interact with cartilage hyaluronic acid to form macromolecular aggregates. Nordihydroguaiaretic acid, a free radical scavenger which, like benoxaprofen, inhibits the lipoxygenase as well as cyclooxygenase pathways of arachidonic acid metabolism, also increased /sup 35/S glycosaminoglycan synthesis in cartilage slices. The stimulation of glycosaminoglycan and protein synthesis by benoxaprofen suggests that its action on the chondrocyte may be different from that of most other nonsteroidal antiinflammatory drugs.
- Research Organization:
- Indiana Univ. School of Medicine, Indianapolis
- OSTI ID:
- 5128766
- Journal Information:
- Arthritis Rheum.; (United States), Journal Name: Arthritis Rheum.; (United States) Vol. 26:6; ISSN ARHEA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ANIMAL TISSUES
ANTIPYRETICS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BIOSYNTHESIS
BODY
BONE JOINTS
CARBOHYDRATES
CARTILAGE
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CONNECTIVE TISSUE
DAYS LIVING RADIOISOTOPES
DRUGS
ENZYMES
EVEN-ODD NUCLEI
GLUCOPROTEINS
IN VITRO
INHIBITION
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
NUCLEI
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
OXYGENASES
PROTEINS
RADIOISOTOPES
SACCHARIDES
SKELETON
SULFUR 35
SULFUR ISOTOPES
SYNTHESIS
TISSUES
TRACER TECHNIQUES
TRITIUM COMPOUNDS