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 3H 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 35S 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.
D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism*; D002396:Catechols / Q000494:pharmacology; D004285:Dogs; D066298:In Vitro Techniques; D007719:Knee Joint / Q000378:metabolism*; D009637:Masoprocol; D011422:Propionates / Q000494:pharmacology*; D011509:Proteoglycans / Q000096:biosynthesis*; D013462:Sulfur Radioisotopes
D002396:Catechols; D011422:Propionates; D011509:Proteoglycans; D013462:Sulfur Radioisotopes; C011677:benoxaprofen; D009637:Masoprocol