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

Vet Surg. Mar-Apr 2001;30(2):132-9. doi: 10.1053/jvet.2001.21399.


Objective: To investigate the potential of doxycycline to reduce stromelysin and inducible nitric oxide synthase (iNOS) activity in dogs with osteoarthritis (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 before surgery. The Doxy-CCl group received 3 to 4 mg/kg doxycycline orally every 24 hours for 7 to 10 days (n = 35). The CCL group received no treatment (n = 46). Synovial fluid, articular cartilage, synovial membrane, and CCL samples were collected during surgery (Doxy-CCL group and CCL group) or immediately after euthanasia from healthy dogs (control group). Synovial fluid samples were examined cytologically. Total nitric oxide (NOt) concentrations were measured in the supernatant of explant cultures of all tissue samples, and stromelysin activity was measured in the supernatant of explant cultures of cartilage.

Results: NOt concentrations measured in cartilage were significantly lower in the Doxy-CCL group than in the CCL group, but were not different from those measured in the control group. Doxycycline treatment did not have a significant 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 OA by inhibiting NO production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anterior Cruciate Ligament / drug effects
  • Anterior Cruciate Ligament / surgery
  • Anterior Cruciate Ligament Injuries*
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / pharmacology*
  • Cartilage, Articular / metabolism
  • Dog Diseases / metabolism*
  • Dog Diseases / surgery
  • Dogs
  • Doxycycline / pharmacokinetics
  • Doxycycline / pharmacology*
  • Matrix Metalloproteinase 3 / biosynthesis*
  • Matrix Metalloproteinase 3 / drug effects
  • Nitric Oxide Synthase / biosynthesis*
  • Nitric Oxide Synthase / drug effects
  • Nitric Oxide Synthase Type II
  • Osteoarthritis, Knee / etiology
  • Osteoarthritis, Knee / metabolism
  • Osteoarthritis, Knee / veterinary*
  • Prospective Studies
  • Rupture / complications
  • Rupture / surgery
  • Rupture / veterinary
  • Synovial Fluid / metabolism


  • Anti-Bacterial Agents
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Matrix Metalloproteinase 3
  • Doxycycline