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10.1002/prp2.224

http://scihub22266oqcxt.onion/10.1002/prp2.224
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suck abstract from ncbi


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pmid27069635
      Pharmacol+Res+Perspect 2016 ; 4 (2 ): e00224
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  • Gastrointestinal safety, chemotherapeutic potential, and classic pharmacological profile of NOSH-naproxen (AVT-219) a dual NO- and H2S-releasing hybrid #MMPMID27069635
  • Chattopadhyay M ; Kodela R ; Duvalsaint PL ; Kashfi K
  • Pharmacol Res Perspect 2016[Apr]; 4 (2 ): e00224 PMID27069635 show ga
  • Naproxen (NAP) is a potent nonsteroidal anti-inflammatory drug (NSAID) with a favorable cardiovascular profile. However, its long-term use may lead to serious gastrointestinal and renal side effects. NOSH- (nitric oxide and hydrogen sulfide) releasing naproxen (NOSH-NAP, AVT-219) belongs to a new class of anti-inflammatory agents designed to overcome these limitations. We compared the gastrointestinal safety, anti-inflammatory, analgesic, antipyretic, and antiplatelet properties of AVT-219 to that of NAP in preclinical animal models. We also evaluated its anticancer effects in 11 human cancer cell (HCC) lines of six different tissue origins and in a chemotherapeutic xenograft mouse model of colon cancer. AVT-219: (1) was orders of magnitude more potent than NAP in inhibiting the growth of cultured HCC; (2) was safe to the stomach, whereas NAP caused significant ulceration; (3) showed strong anti-inflammatory, analgesic, antipyretic, and antiplatelet properties comparable to NAP; and (4) NAP caused a significant rise in plasma tumor necrosis factor-alpha (TNF?), whereas in the AVT-219-treated rats this rise was significantly less. Mechanistically, AVT-219 was a strong antioxidant, inhibited cyclooxygenase (COX)-1 and -2, thus reducing prostaglandin (PG) E2. In xenografts, AVT-219 significantly reduced tumor growth and tumor mass with no sign of GI toxicity, whereas NAP-treated mice died due to GI bleeding. AVT-219 displayed considerable safety and potency in inhibiting HCC growth; was an effective analgesic, antipyretic, antiplatelet, and anti-inflammatory; and was significantly more efficacious than NAP in reducing the growth of established tumors in a xenograft mouse model.
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