Jp. Pelletier et al., Reduction in the structural changes of experimental osteoarthritis by a nitric oxide inhibitor, OSTEO CART, 7(4), 1999, pp. 416-418
Objective: To evaluate the in-vivo therapeutic efficacy of N-iminoethyl-L-L
ysine (L-NIL), a selective inhibitor of inducible nitric oxide synthase (iN
OS) in a dose response study, on the progression of lesions in the experime
ntal osteoarthritic (OA) dog model.
Design: The sectioning of the anterior cruciate ligament of the right stifl
e 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 rece
ived oral L-NIL (0.3, 1 or 10 mg/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 a
t the highest dosage tested (3 and 10 mg/kg/day).
Conclusions: This study confirms the effectiveness of L-NIL, a selective in
hibitor of iNOS, in attenuating the progression of experimental OA. It also
clearly shows that the effect is dose-dependent.