[Effects of orally available prodrug of cromoglycic acid on collagen-induced arthritis mice].
Cromoglicate lisetil (CL) is an orally deliverable prodrug of cromoglycic acid, having diethyl promoieties and a lysyl promoiety for its optimum drug-delivery. We examined the effects of CL on bovine type II collagen (CII)-induced arthritis (CIA) of male DBA/1J mice, an experimental model for human rheumatoid arthritis, and its action mechanism. CL (100 mg/kg/day) was given by gavage to CII-immunized mice once daily for 6 weeks, starting when arthritic symptoms became evident. Symptomatic scores of arthritis obviously elevated in non-treated CIA mice at week 6.5 after initial immunization and continued elevated thereafter throughout the experiment, the elevation which was reduced by CL. CL also improved radiographic score of phalangeal destruction and pathohistological indexes at the end of treatment period. Serum anti-CII antibody titer was increased in non-treated CIA mice and the elevation was reduced by CL treatment. Mast cells (MCs) number in arthritic region was increased in non-treated CIA mice but not by CL treatment. In conclusion, oral CL treatment proved beneficial in CIA mice. Observed correlation between the CL effect on CIA and that on MCs number suggests the potential contribution of MCs to accelerate chronic arthritic processes and may further implicate potential action mechanism of CL, which may act by regulating MC functions for chronic inflammation.
Kobayashi
Y
Y
Department of Pharmacology, Shimane Medical University, Japan.
Shirahase
H
H
Zhao
H F
HF
Kakizoe
E
E
Okunishi
H
H
D000284:Administration, Oral; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage*; D000906:Antibodies / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D002908:Chronic Disease; D003094:Collagen / Q000276:immunology; D004205:Cromolyn Sodium / Q000008:administration & dosage*; D004195:Disease Models, Animal; D008297:Male; D008407:Mast Cells / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D011355:Prodrugs
D018927:Anti-Asthmatic Agents; D000906:Antibodies; D011355:Prodrugs; D003094:Collagen; D004205:Cromolyn Sodium