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 osteoarthritis (OA) secondary to spontaneous cranial cruciate ligament (CCL) rupture.


METHODS
Prospective, clinical study.


METHODS
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.


CONCLUSIONS
The findings in this study indicate that doxycycline inhibits NO production in cartilage in dogs with CCL rupture.


CONCLUSIONS
Doxycycline may have a role in the treatment of canine OA by inhibiting NO production.
Department of Small Animal Surgery and Orthopedics, Faculty of Veterinary Medicine, University of Bern, Switzerland.
S
S
Jauernig
A
A
Schweighauser
M
M
Reist
B
B
Von Rechenberg
P
P
Schawalder
D
D
Spreng
D000818:Animals; D016118:Anterior Cruciate Ligament / Q000187:drug effects / Q000601:surgery; D000070598:Anterior Cruciate Ligament Injuries; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000378:metabolism; D004283:Dog Diseases / Q000378:metabolism* / Q000601:surgery; D004285:Dogs; D004318:Doxycycline / Q000493:pharmacokinetics / Q000494:pharmacology*; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis* / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II; D020370:Osteoarthritis, Knee / Q000209:etiology / Q000378:metabolism / Q000662:veterinary*; D011446:Prospective Studies; D012421:Rupture / Q000150:complications / Q000601:surgery / Q000662:veterinary; D013582:Synovial Fluid / Q000378:metabolism
D000900:Anti-Bacterial Agents; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D019278:Matrix Metalloproteinase 3; D004318:Doxycycline