The effect of sulfasalazine on homocysteine metabolism in vivo

Abstract

Sulfasalazine (SSZ) is a disease‐modifying antirheumatic drug (DMARD) commonly used in the treatment of rheumatoid arthritis that inhibits intestine folate absorption and multiple folate‐dependent enzymes. The objective of the present study was to systematically investigate the impacts of long‐term SSZ treatment on homocysteine metabolism in vivo. C57BL/6J mice received either sterile 0.5% cellulose i.p. (vehicle, control group) or SSZ (80 mg/kg/day) for 8 weeks. Folate, S‐adenosyl methionine (adoMet), S‐adenosylhomocysteine (adoHcy) and homocysteine were determined in blood and tissues. Whole blood adoMet levels were significantly elevated compared to subjects on other DMARDs (1807 ± 1346, vs. 330 ± 861, p < 0.001), suggesting that SSZ may increase adoMet synthesis or decrease adoMet utilization. Furthermore, whole blood adoMet levels significantly correlated with the weekly dosage of SSZ (r = 0.34, p = 0.002) in patients receiving SSZ (n = 63).SSZ did not alter adoMet, adoHcy, methionine adenosyltransferase (MAT) activity and methylated cytidine content of DNA (dMC%) in mice liver or kidney. SSZ treatment increased whole blood adoMet level by induction of the methionine adenosyltransferase activity in erythrocytes in mice. In the present study we demonstrated the novel finding of a direct inducing effect of SSZ treatment on adoMet synthesis and adoMet synthase activity in blood.Grant Funding Source: ASN