NOSH-sulindac (AVT-18A) is a novel nitric oxide- and hydrogen sulfide-releasing hybrid that is gastrointestinal safe and has potent anti-inflammatory, analgesic, antipyretic, anti-platelet, and anti-cancer properties

摘要: Sulindac is chemopreventive and has utility in patients with familial adenomatous polyposis; however, side effects preclude its long-term use. NOSH-sulindac (AVT-18A) releases nitric oxide hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, anti-pyretic, anti-platelet, anti-cancer properties of sulindac administered orally rats at equimolar doses. Gastrointestinal safety: 6h post-administration, number/size hemorrhagic lesions stomachs were counted. Tissue samples frozen for PGE2, SOD, MDA determination. Anti-inflammatory: 1h after drug administration, volume carrageenan-induced rat paw edemas measured 5h. Anti-pyretic: fever induced by LPS (ip) an hour before administration test drugs, core body temperature hourly Analgesic: time-dependent analgesic evaluated hyperalgesia. Antiplatelet: anti-aggregatory studied on collagen-induced platelet aggregation human platelet-rich plasma. Anti-cancer: We examined growth 12 cancer cell lines six different tissue origins. Both agents reduced PGE2 levels stomach tissue; did not cause any ulcers, whereas caused significant bleeding. Lipid peroxidation higher than that from NOSH-sulindac. SOD activity significantly lowered but increased showed similar anti-platelet activities. plasma TNFα this rise lower NOSH-sulindac-treated animals. inhibited all studied, potencies 1000- 9000-fold greater sulindac. proliferation, apoptosis, G2/M cycle block. These results demonstrate safe, maintains antipyretic, antiplatelet parent compound sulinsac, anti-growth against wide variety cells.