Sepiapterin Reductase Inhibition Leading to Selective Reduction of Inflammatory Joint Pain in Mice and Increased Urinary Sepiapterin Levels in Humans and Mice

• Published in: Arthritis & rheumatology (Hoboken, N.J.) Vol. 72; no. 1; pp. 57 - 66
• Main Authors: Fujita, Masahide, Scheffer, Débora da Luz, Turnes, Bruna Lenfers, Cronin, Shane J. F., Latrémolière, Alban, Costigan, Michael, Woolf, Clifford J., Latini, Alexandra, Andrews, Nick A.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.01.2020
• Subjects: Adult; Alcohol Oxidoreductases - antagonists & inhibitors; Analgesics; Animals; Antibodies; Antirheumatic Agents - pharmacology; Arthritis; Arthritis, Experimental - pathology; Arthritis, Experimental - physiopathology; Biomarkers; Biomarkers - urine; Biopterins - analogs & derivatives; Biopterins - urine; Chromatography, High Pressure Liquid; Cold Temperature; Collagen; Female; Heat; Hindlimb; Hot Temperature; Humans; Hyperalgesia; Hyperesthesia - physiopathology; Hypersensitivity; Inflammation; Inhibition; Inhibitors; Joint diseases; Joints (anatomy); Joints - drug effects; Joints - pathology; Liquid chromatography; Male; Mice; Pain; Pain perception; Pain sensitivity; Pain Threshold - drug effects; Pterins - urine; Reductases; Rheumatoid arthritis; Sepiapterin reductase; Sulfasalazine; Sulfasalazine - pharmacology; Tetrahydrobiopterin

Objective To evaluate the antiinflammatory and analgesic effects of sepiapterin reductase (SPR) inhibition in a mouse model of inflammatory joint disease, and to determine whether urinary sepiapterin levels, as measured in mice and healthy human volunteers, could be useful as a noninvasive, translat...