Reduction in the structural changes of experimental osteoarthritis by a nitric oxide inhibitor.
OBJECTIVE
To evaluate the in-vivo therapeutic efficacy of N -iminoethyl-L-Lysine (L-NIL), a selective inhibitor of inducible nitric oxide synthase (iNOS) in a dose response study, on the progression of lesions in the experimental osteoarthritic (OA) dog model.


METHODS
The sectioning of the anterior cruciate ligament of the right stifle joint of mongrel dogs was done by a stab wound. Dogs were separated into experimental groups: Group 1 received no treatment, Groups 2, 3, and 4 received oral L-NIL (0.3, 1 or 10mg/kg/day, respectively) starting immediately after surgery. The OA dogs were killed at 12 weeks after surgery.


RESULTS
Macroscopically, L-NIL decreased the size of the cartilage lesions on condyles and plateaus. The histologic severity of the cartilage lesions was decreased in the L-NIL-treated dogs. This effect was more pronounced at the highest dosage tested (3 and 10mg/kg/day).


CONCLUSIONS
This study confirms the effectiveness of L-NIL, a selective inhibitor of iNOS, in attenuating the progression of experimental OA. It also clearly shows that the effect is dose-dependent.
Pelletier
J
J
Osteoarthritis Research Unit, Louis-Charles Simard Research Center, Centre hospitalier de l'Université de Montréal, Campus Notre-Dame, Montréal, Québec, Canada.
Jovanovic
D
D
Fernandes
J C
JC
Manning
P
P
Connor
J R
JR
Currie
M G
MG
Martel-Pelletier
J
J
D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D008239:Lysine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010003:Osteoarthritis / Q000188:drug therapy* / Q000473:pathology
C090663:N(6)-(1-iminoethyl)lysine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D008239:Lysine