Here, we describe the improved antiarthritic properties of a
nitric oxide-releasing derivative of
prednisolone that includes a sparing of the effects on bone.
Glucocorticoids are widely used in the treatment of chronic inflammatory pathologies, but their use is often accompanied by side effects, including
osteoporosis. Recently, a new
steroid able to release low levels of
nitric oxide showed potent inhibition of leukocyte trafficking and
chemokine generation in models of acute
inflammation. The objective of this study was to assess the anti-inflammatory activity of this
nitric-oxide releasing
glucocorticoid, nitro-
prednisolone (NCX-1015), in parallel with the parent compound
prednisolone and a control molecule lacking an NO group, (NCX-1016), in a model of rat
collagen-induced arthritis. Dosing of rats with
NCX-1015 (0.4-4 micromol/kg, i.p.) greatly reduced all parameters of
inflammation. A significant but inferior anti-inflammatory effect also was obtained with
prednisolone.
Collagen-induced arthritic rats had elevated
pyridinoline values (> 60% over naïve rats), indicating bone and cartilage erosion; this increase was prevented by
NCX-1015 but not by
prednisolone or NCX-1016 treatment. In vitro,
prednisolone (1 nM), but not
NCX-1015, elevated
bone resorbing activity of rat primary osteoclasts. In conclusion,
NCX-1015 is a
steroid derivative with a potential for the treatment of chronic inflammatory pathologies and that has milder side effects anticipated on the bone compartment.