NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid has enhanced chemo-preventive properties compared to aspirin, is gastrointestinal safe with all the classic therapeutic indications

Biochem Pharmacol. 2015 Dec 15;98(4):564-72. doi: 10.1016/j.bcp.2015.09.014. Epub 2015 Sep 21.


Aspirin is chemopreventive; however, side effects preclude its long-term use. NOSH-aspirin (NBS-1120), a novel hybrid that releases nitric oxide and hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, anti-pyretic, anti-platelet, and chemopreventive properties of aspirin and NBS-1120 administered orally to rats at equimolar doses. Gastrointestinal safety: 6h post-administration, the number and size of hemorrhagic lesions in stomachs were counted; tissue samples were frozen for PGE2, SOD, and MDA determination. Anti-inflammatory: 1h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 5h. Anti-pyretic: fever was induced by LPS (ip) an hour before administration of the test drugs, core body temperature was measured hourly for 5h. Analgesic: time-dependent analgesic effects were evaluated by carrageenan-induced hyperalgesia. Antiplatelet: anti-aggregatory effects were studied on collagen-induced platelet aggregation of human platelet-rich plasma. Chemoprevention: nude mice were gavaged daily for 25 days with vehicle, aspirin or NBS-1120. After one week, each mouse was inoculated subcutaneously in the right flank with HT-29 human colon cancer cells. Both agents reduced PGE2 levels in stomach tissue; however, NBS-1120 did not cause any stomach ulcers, whereas aspirin caused significant bleeding. Lipid peroxidation induced by aspirin was higher than that exerted by NBS-1120. SOD activity was significantly inhibited by aspirin but increased by NBS-1120. Both agents showed similar anti-inflammatory, analgesic, anti-pyretic, and anti-platelet activities. Aspirin increased plasma TNFα more than NBS-1120-treated animals. NBS-1120 was better than aspirin as a chemopreventive agent; it dose-dependently inhibited tumor growth and tumor mass.

Keywords: Aspirin; Chemopreventive; GI-sparing; Hydrogen sulfide; Nitric oxide.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Aspirin / analogs & derivatives*
  • Aspirin / pharmacology
  • Aspirin / therapeutic use
  • Chemoprevention / methods*
  • Disulfides / pharmacology
  • Disulfides / therapeutic use*
  • Dose-Response Relationship, Drug
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / metabolism*
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / metabolism
  • HT29 Cells
  • Humans
  • Hydrogen Sulfide / metabolism*
  • Male
  • Mice
  • Mice, Nude
  • Nitrates / pharmacology
  • Nitrates / therapeutic use*
  • Nitric Oxide / metabolism*
  • Rats
  • Rats, Wistar
  • Xenograft Model Antitumor Assays / methods


  • 4-(3-thioxo-3H-1,2-dithiol-5-yl)phenyl 2-((4-(nitrooxy)butanoyl)oxy)benzoate
  • Anti-Inflammatory Agents, Non-Steroidal
  • Disulfides
  • Nitrates
  • Nitric Oxide
  • Aspirin
  • Hydrogen Sulfide