Limits...
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.

Kashfi K, Chattopadhyay M, Kodela R - Redox Biol (2015)

Bottom Line: Gastrointestinal safety: 6h post-administration, number/size of hemorrhagic lesions in stomachs were counted.Both agents reduced PGE2 levels in stomach tissue; however, NOSH-sulindac did not cause any stomach ulcers, whereas sulindac caused significant bleeding.These results demonstrate that NOSH-sulindac is gastrointestinal safe, and maintains the anti-inflammatory, analgesic, antipyretic, and antiplatelet properties of its parent compound sulinsac, with anti-growth activity against a wide variety of human cancer cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Pharmacology and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, New York, United States; Avicenna Pharmaceuticals Inc., New York, NY, United States. Electronic address: kashfi@med.cuny.edu.

No MeSH data available.


Related in: MedlinePlus

Sulindac and NOSH-sulindac reduce LPS-induced fever, raise the threshold for hyperalgesia, and show anti-platelet activity. Panel A: LPS (50 μg/kg, ip) was administered to the rats one hour before administration of SUL or NOSH-SUL at equimolar doses (0.56 mmol/kg; 200 mg/kg and 467 mg/kg for SUL and NOSH-SUL, respectively). Core body temperature was recorded at 30 min and thereafter hourly for 5 h. Results are mean±SEM for 5 rats in each group, *P<0.01 vs vehicle for both SUL and NOSH-SUL from 1–5 h. Panel B: Mechanical pain threshold was increased in a time-dependent manner by SUL and NOSH-SUL. Results are mean±SEM for 5 rats in each group. *P<0.05 vs vehicle for SUL and NOSH-SUL from 2–5 h.Panel C: SUL and NOSH-SUL were equally effective in inhibiting human platelet aggregation. Results are mean±range for two individuals.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4556776&req=5

f0030: Sulindac and NOSH-sulindac reduce LPS-induced fever, raise the threshold for hyperalgesia, and show anti-platelet activity. Panel A: LPS (50 μg/kg, ip) was administered to the rats one hour before administration of SUL or NOSH-SUL at equimolar doses (0.56 mmol/kg; 200 mg/kg and 467 mg/kg for SUL and NOSH-SUL, respectively). Core body temperature was recorded at 30 min and thereafter hourly for 5 h. Results are mean±SEM for 5 rats in each group, *P<0.01 vs vehicle for both SUL and NOSH-SUL from 1–5 h. Panel B: Mechanical pain threshold was increased in a time-dependent manner by SUL and NOSH-SUL. Results are mean±SEM for 5 rats in each group. *P<0.05 vs vehicle for SUL and NOSH-SUL from 2–5 h.Panel C: SUL and NOSH-SUL were equally effective in inhibiting human platelet aggregation. Results are mean±range for two individuals.

Mentions: It is well known that NSAIDs exert a moderate antipyretic effect when administered orally; although SUL is seldom used for that purpose. Nevertheless for comparison considerations, we wanted to determine the decrease in body temperature induced by NOSH-SUL compared to that obtained with SUL. Experimental drugs, SUL and NOSH-SUL were administered orally at equimolar doses (0.56 mmol/kg; 200 mg/kg and 467 mg/kg for SUL and NOSH-SUL, respectively) 30 min before injecting the rats with LPS (50 μg/kg ip). In this regard, control animals showed a time-dependent increase in body temperature which leveled off between 3 and 4 h with ΔT=1.8 °C and this was maintained until the end of the screen (5 h). However, SUL and NOSH-SUL-treated animals showed only about a half-degree increase in body temperature at 30 min after LPS injection, this increased to ΔT=0.7 °C by 1 h thereafter gradually decreased (Fig. 6A).


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.

Kashfi K, Chattopadhyay M, Kodela R - Redox Biol (2015)

Sulindac and NOSH-sulindac reduce LPS-induced fever, raise the threshold for hyperalgesia, and show anti-platelet activity. Panel A: LPS (50 μg/kg, ip) was administered to the rats one hour before administration of SUL or NOSH-SUL at equimolar doses (0.56 mmol/kg; 200 mg/kg and 467 mg/kg for SUL and NOSH-SUL, respectively). Core body temperature was recorded at 30 min and thereafter hourly for 5 h. Results are mean±SEM for 5 rats in each group, *P<0.01 vs vehicle for both SUL and NOSH-SUL from 1–5 h. Panel B: Mechanical pain threshold was increased in a time-dependent manner by SUL and NOSH-SUL. Results are mean±SEM for 5 rats in each group. *P<0.05 vs vehicle for SUL and NOSH-SUL from 2–5 h.Panel C: SUL and NOSH-SUL were equally effective in inhibiting human platelet aggregation. Results are mean±range for two individuals.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556776&req=5

f0030: Sulindac and NOSH-sulindac reduce LPS-induced fever, raise the threshold for hyperalgesia, and show anti-platelet activity. Panel A: LPS (50 μg/kg, ip) was administered to the rats one hour before administration of SUL or NOSH-SUL at equimolar doses (0.56 mmol/kg; 200 mg/kg and 467 mg/kg for SUL and NOSH-SUL, respectively). Core body temperature was recorded at 30 min and thereafter hourly for 5 h. Results are mean±SEM for 5 rats in each group, *P<0.01 vs vehicle for both SUL and NOSH-SUL from 1–5 h. Panel B: Mechanical pain threshold was increased in a time-dependent manner by SUL and NOSH-SUL. Results are mean±SEM for 5 rats in each group. *P<0.05 vs vehicle for SUL and NOSH-SUL from 2–5 h.Panel C: SUL and NOSH-SUL were equally effective in inhibiting human platelet aggregation. Results are mean±range for two individuals.
Mentions: It is well known that NSAIDs exert a moderate antipyretic effect when administered orally; although SUL is seldom used for that purpose. Nevertheless for comparison considerations, we wanted to determine the decrease in body temperature induced by NOSH-SUL compared to that obtained with SUL. Experimental drugs, SUL and NOSH-SUL were administered orally at equimolar doses (0.56 mmol/kg; 200 mg/kg and 467 mg/kg for SUL and NOSH-SUL, respectively) 30 min before injecting the rats with LPS (50 μg/kg ip). In this regard, control animals showed a time-dependent increase in body temperature which leveled off between 3 and 4 h with ΔT=1.8 °C and this was maintained until the end of the screen (5 h). However, SUL and NOSH-SUL-treated animals showed only about a half-degree increase in body temperature at 30 min after LPS injection, this increased to ΔT=0.7 °C by 1 h thereafter gradually decreased (Fig. 6A).

Bottom Line: Gastrointestinal safety: 6h post-administration, number/size of hemorrhagic lesions in stomachs were counted.Both agents reduced PGE2 levels in stomach tissue; however, NOSH-sulindac did not cause any stomach ulcers, whereas sulindac caused significant bleeding.These results demonstrate that NOSH-sulindac is gastrointestinal safe, and maintains the anti-inflammatory, analgesic, antipyretic, and antiplatelet properties of its parent compound sulinsac, with anti-growth activity against a wide variety of human cancer cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Pharmacology and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, New York, United States; Avicenna Pharmaceuticals Inc., New York, NY, United States. Electronic address: kashfi@med.cuny.edu.

No MeSH data available.


Related in: MedlinePlus