Glucosamine and adjuvant arthritis: a pharmacokinetic and pharmacodynamic study.
We investigated (i) the effectiveness of glucosamine (GlcN) in treating adjuvant arthritis (AA) and its cardiac abnormalities (down regulation of cardiac calcium channel and beta-adrenergic proteins) (ii) the effect of AA on pharmacokinetics of GlcN and the cardiac ryanodine-2 target protein. Six groups (n=6/group) of male Sprague-Dawley rats were treated with Mycobacterium butyricum (Inflamed) or saline (Control). One group received GlcN hydrochloride (300mg/kg/day, p.o. commenced on day one); others received GlcN upon developing the early sign of AA; after amelioration of the disease, the GlcN administration continued for one group while discontinued for another. Subsequently, a 25mg/kg verapamil administered, electrocardiographs were recorded and pharmacokinetic delineated. Serum nitrite concentration, body weight, paw thickness and arthritis index were assessed. Cardiac contents of L-type calcium channel, β1-adrenoreceptors and ryanodine-2 receptor were measured. All rats that received M. butyricum, but not GlcN, developed arthritis. GlcN prevented arthritis and improved the signs and symptoms after their emergence. It also restores the down-regulating effect of AA on the cardiac target proteins, pharmacokinetics and response to verapamil. Inflammation did not influence pharmacokinetics of GlcN and the density of ryanodine-2 protein. GlcN has controlling effect on AA and restores the down-regulating effect of AA on cardiac proteins and response to verapamil, perhaps, through its anti-inflammatory properties.
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada T6G 2N8.
Mohammad H
MH
Gilzad-Kohan
Fakhreddin
F
Jamali
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics; D020746:Calcium Channels, L-Type / Q000378:metabolism; D005944:Glucosamine / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D014700:Verapamil / Q000493:pharmacokinetics
D000889:Anti-Arrhythmia Agents; D000893:Anti-Inflammatory Agents; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D009573:Nitrites; D018342:Receptors, Adrenergic, beta-1; D019837:Ryanodine Receptor Calcium Release Channel; D014700:Verapamil; D005944:Glucosamine