The effects of doxycycline on nitric oxide and stromelysin production in dogs with cranial cruciate ligament rupture

Objective-To investigate the potential of doxycycline to reduce stromelysin and inducible nitric oxide synthase (iNOS) activity in dogs with osteoarth ritis (OA) secondary to spontaneous cranial cruciate ligament (CCL) rupture . Study Design-Prospective, clinical study. Animals-Eighty-one dogs with OA secondary to CCL rupture and 54 normal dogs . Methods-Dogs with OA secondary to CCL rupture were divided into 2 groups be fore surgery. The Doxy-CCl group received 3 to 4 mg/kg doxycycline orally e very 24 hours for 7 to 10 days (n = 35). The CCL group received no treatmen t (n = 46). Synovial fluid, articular cartilage, synovial membrane, and CCL samples were collected during surgery (Doxy-CCL group and CCL group) or im mediately after euthanasia from healthy dogs (control group). Synovial flui d samples were examined cytologically. Total nitric oxide (NOt) concentrati ons were measured in the supernatant of explant cultures of all tissue samp les, and stromelysin activity was measured in the supernatant of explant cu ltures of cartilage. Results-NOt concentrations measured in cartilage were significantly lower i n the Doxy-CCL group than in the CCL group, but were not different from tho se measured in the control group. Doxycycline treatment did not have a sign ificant effect on cartilage stromelysin levels. Conclusion-The findings in this study indicate that doxycycline inhibits NO production in cartilage in dogs with CCL rupture. Clinical Relevance-Doxycycline may have a role in the treatment of canine O A by inhibiting NO production. (C) Copyright 2001 by The American College o f Veterinary Surgeons.