Fr134 SARS-COV-2 INDUCES EPITHYELIAL-NEURONAL CROSSTALK STIMULATING VASOACTIVE INTESTINAL PEPTIDE RELEASE AS A POTENTIAL MECHANISM OF COVID-19-ASSOCIATED DIARRHEA

SOCS3 and CREB.Ketoprofen but not ATB-352 increased the intestinal abundance for Romboutsia, Lactobacillus and Clostridium Sensu Stricto 1.Both compounds exerted similar effectiveness related to cyclooxygenases (COXs) activity inhibition reflected as decreased PGE 2 production in GI mucosa.Polypharmacy with ASA enhanced ketoprofen-toxicity but did not affect GI-safety of ATB-352.Omeprazole decreased ketoprofen-induced injury score to the level of ATB-352 applied alone.CONCLUSIONS: ATB-352 applied alone or in polypharmacy with aspirin effectively inhibits COX activity, is GI-safe due to its H 2 S-releasing ability and has lower impact on molecular oxidative-or inflammatory-response pathways and intestinal microbiome composition as compared with its parent drug.We conclude that GI-safety of H 2 S-releasing ketoprofen does not require polypharmacy with PPIs and involves maintenance of intestinal microbiota profile and HMOX-1, CREB and SOCS3 pathways activation.