TRK-530 inhibits accumulation of superoxide anions derived from human polymorphonuclear leukocytes and bone resorption induced by activated osteoclasts.
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.
Tanahashi
M
M
Toray Industries, Inc., Basic Research Laboratories, Kanagawa, Japan. tanahash@blab.toray.co.jp
Funaba
Y
Y
Tateishi
A
A
Kawabe
N
N
Nakadate-Matsushita
T
T
D000818:Animals; D000833:Animals, Suckling; D000975:Antioxidants / Q000494:pharmacology*; D001862:Bone Resorption / Q000188:drug therapy*; D002117:Calcitriol; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004164:Diphosphonates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D012968:Etidronic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006614:Hindlimb; D006801:Humans; D051379:Mice; D009240:N-Formylmethionine Leucyl-Phenylalanine; D018375:Neutrophil Activation; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects; D000068296:Risedronic Acid; D013481:Superoxides / Q000378:metabolism*
D000975:Antioxidants; D002121:Calcium Channel Blockers; D004164:Diphosphonates; C109548:TRK 530; D013481:Superoxides; C071542:cimadronate; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002117:Calcitriol; D000068296:Risedronic Acid; D012968:Etidronic Acid