{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:24:59Z","timestamp":1792610699498,"version":"4.5.0"},"reference-count":48,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T00:00:00Z","timestamp":1636588800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>In our previous studies, a ketorolac\u2013galactose conjugate (ketogal) showed prolonged anti-inflammatory and analgesic activity, causing less gastric ulcerogenic effect and renal toxicity than its parent drug ketorolac. In order to demonstrate the safer profile of ketogal compared to ketorolac, histopathological changes in the small intestine and liver using three staining techniques before and after repeated oral administration in mice with ketorolac or an equimolecular dose of its galactosylated prodrug ketogal were assessed. Cytotoxicity and oxidative stress parameters were evaluated and compared in ketorolac- and ketogal-treated Human Primary Colonic Epithelial cells at different concentrations and incubation times. Evidence of mitochondrial oxidative stress was found after ketorolac treatment; this was attributable to altered mitochondrial membrane depolarization and oxidative stress parameters. No mitochondrial damage was observed after ketogal treatment. In ketorolac-treated mice, severe subepithelial vacuolation and erosion with inflammatory infiltrates and edematous area in the intestinal tissues were noted, as well as alterations in sinusoidal spaces and hepatocytes with foamy cytoplasm. In contrast, treatment with ketogal provided a significant improvement in the morphology of both organs. The prodrug clearly demonstrated a safer profile than its parent drug both in vitro and ex vivo, confirming that ketogal is a strategic alternative to ketorolac.<\/jats:p>","DOI":"10.3390\/ph14111149","type":"journal-article","created":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T23:04:46Z","timestamp":1636671886000},"page":"1149","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Ketogal Safety Profile in Human Primary Colonic Epithelial Cells and in Mice"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2013-4893","authenticated-orcid":false,"given":"Federica","family":"Sodano","sequence":"first","affiliation":[{"name":"Department of Drug Science and Technology, University of Torino, 10125 Torino, Italy"},{"name":"Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5355-1557","authenticated-orcid":false,"given":"Bice","family":"Avallone","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Naples Federico II, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Tizzano","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Naples Federico II, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0868-2520","authenticated-orcid":false,"given":"Chiara","family":"Fogliano","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Naples Federico II, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Rolando","sequence":"additional","affiliation":[{"name":"Department of Drug Science and Technology, University of Torino, 10125 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0939-0562","authenticated-orcid":false,"given":"Elena","family":"Gazzano","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Systems Biology, University of Torino, 10123 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9787-4836","authenticated-orcid":false,"given":"Chiara","family":"Riganti","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Torino, 10126 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9022-8487","authenticated-orcid":false,"given":"Salvatore","family":"Magliocca","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariarosaria","family":"Cuozzo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Albrizio","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Calignano","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4806-1764","authenticated-orcid":false,"given":"Claudia","family":"Cristiano","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5950-1617","authenticated-orcid":false,"given":"Roberto","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Rimoli","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4S","DOI":"10.1016\/S0002-9343(00)00627-6","article-title":"Nonsteroidal anti-inflammatory drug prescribing: Past, present, and future","volume":"110","author":"Jones","year":"2001","journal-title":"Am. 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