TRK-530 Inhibits Accumulation of Superoxide Anions Derived from Human Polymorphonuclear Leukocytes and Bone Resorption Induced by Activated Osteoclasts

Abstract

TRK-530, a newly synthesized bisphosphonate, was assessed for its effects on the accumulation of superoxide anions derived from human formyl-methionyl-leucyl-phenylalanine-stimulated polymorphonuclear leukocytes (PMN), and for its effects on bone resorption using a pit formation assay. TRK-530 concentration-dependently inhibited superoxide accumulation derived from PMN and osteoclast pit formation stimulated by 1,25-dihydroxyvitamin D₃. Incadronate and risedronate had a strong inhibitory effect on pit formation, but no antioxidative activity. These data suggest that the anti-bone resorption activities of TRK-530 are possibly unrelated to its antioxidant properties. However, it is difficult to conclude at present which mechanisms play the most important role in the anti-bone resorption activities of TRK-530.

Inhibitory Effect of a Novel Bisphosphonate, TRK‐530, on Dental Calculus Formation in Rats

“…In addition to the anticalculogenic effect of TRK-530 in this study, it has also been reported 13,14 to have an anti-inflammatory effect in rat adjuvant arthritis and anti-bone-resorbing activity in systemic administration. The anti-inflammatory and anti-bone resorption effects of this drug suggest that, if facilitated with the mucosal permeability of the gingiva, it may even be effective for inhibiting gingival inflammation and periodontal bone resorption when topically applied.…”

“…It was also found that TRK-530 has an inhibitory effect on osteoclastic bone resorption. 14 In the field of periodontology, a drug of choice has been sought which would help to eliminate gingival and periodontal inflammation, suppress alveolar bone resorption, and inhibit dental calculus. Since BPs are generally characterized by their physico-chemical inhibitory effects on calciumphosphate crystal formation in vitro, TRK-530 may have an anticalculogenic effect, in addition to its antiinflammatory and anti-bone-resorbing activities.…”

Pharmacological Topics of Bone Metabolism: A Novel Bisphosphonate for the Treatment of Periodontitis

“…The expression of cyclooxygenase (COX)-2 mRNA and COX-2 protein was also prevented. Since TRK-530 has an anti-oxidant side chain (6) and can inhibit the generation of superoxide anion that reacts with nitric oxide (NO) to form peroxynitrite (ONOO − ), which is known to be a potent stimulator of COX-2 expression, the inhibi- Fig. 4.…”

Effects of Local Administration of Novel Bisphosphonate Disodium Dihydrogen-4-[(Methylthio) Phenylthio] Methane- Bisphosphonate (MPMBP) on the Healing of Femoral Bone Defects in Wistar Rats

“…Takizawa, et al reported that whole body administration of MPMBP hindered bone resorption in OVX rats 11) . Additionally, it was reported that in vitro and in vivo examinations showed the suppression of osteoclasts activity 13,14) . Our results showed that the MPMBP suppressed the appearance and differentiation of osteoclasts in the administration site of the MPMBP.…”