The influence of phenylbutazone on the zinc level in serum and paw tissue of rats with adjuvant arthritis.

Our problem was, can phenylbutazone influence zinc level in serum and paw tissue and is there any relationship to its antiinflammatory effect? Phenylbutazone and zinc concentration were photometrically determined in serum and in homogenated paw tissue of rats injected with Freund's adjuvant. The course of total serum zinc level is opposite to the course of paw swelling whereas zinc content of paw tissue increases with swelling in the first phase of arthritis. Phenylbutazone increases serum zinc level, and the increase is highest if phenylbutazone is given daily. Phenylbutazone slightly decreases paw zinc level, especially 5 and 12 hrs after administration, but only in the first phase of arthritis. Pharmacokinetics of phenylbutazone in serum is unaffected in arthritic rats whereas phenylbutazone content of paws is increased in the first and second phase of arthritis. When given alone zinc and phenylbutazone accumulate in the inflamed tissue, perhaps, in their plasma protein bound form. Phenylbutazone inhibits inflammation and concomitantly decreases invasion of proteins and protein-bound zinc into the paw. Possibly phenylbutazone inhibits inflammation by inhibition of zinc-containing dehydrogenases since such enzymes are inhibited in vitro by phenylbutazone.