Inhibition of glycosaminoglycan synthesis in anatomically intact rat patellar cartilage by paracetamol-induced serum sulfate depletion.
We have studied the effect of low sulfate concentrations on the glycosaminoglycan synthesis in rat patellar cartilage in vivo as well as in vitro. The oral administration of 200 mg/kg paracetamol to male Wistar rats resulted in a significant reduction of the serum sulfate concentration. Reduced serum sulfate availability resulted in a 34% decrease of glycosaminoglycan synthesis in patellar cartilage. This is due to sulfate depletion since paracetamol had no direct effects on glycosaminoglycan synthesis and a slight but significant inhibitory effect on the catabolism of radiolabeled glycosaminoglycans in vitro. The glycosaminoglycans synthesized at low sulfate concentrations in vivo were similar to the glycosaminoglycans synthesized at physiological sulfate concentrations. Studying the effect of sulfate availability in vitro on glycosaminoglycan synthesis in patellar cartilage we found that incubation of rat patellae in medium containing less than 0.5 mM inorganic sulfate led to a decreased sulfate incorporation. The use of potential sulfate decreasing drugs can lead to inhibition of glycosaminoglycan synthesis. This argues for a reconsideration of the use of these drugs in patients with already dysfunctioning cartilage metabolism as in rheumatoid arthritis and osteoarthrosis.
van der Kraan
P M
PM
Department of Rheumatology, Academic Hospital St. Radboud, University of Nijmegen, The Netherlands.
de Vries
B J
BJ
Vitters
E L
EL
van den Berg
W B
WB
van de Putte
L B
LB
D000082:Acetaminophen / Q000494:pharmacology*; D000818:Animals; D002356:Cartilage / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012459:Salicylates / Q000494:pharmacology; D020156:Salicylic Acid; D013431:Sulfates / Q000097:blood*
D006025:Glycosaminoglycans; D012459:Salicylates; D013431:Sulfates; D000082:Acetaminophen; D020156:Salicylic Acid