{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T23:58:33Z","timestamp":1778111913553,"version":"3.51.4"},"reference-count":70,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T00:00:00Z","timestamp":1669680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MIUR","award":["PRIN2017SXEXT5"],"award-info":[{"award-number":["PRIN2017SXEXT5"]}]},{"name":"MIUR","award":["RFO21"],"award-info":[{"award-number":["RFO21"]}]},{"name":"University of Bologna","award":["PRIN2017SXEXT5"],"award-info":[{"award-number":["PRIN2017SXEXT5"]}]},{"name":"University of Bologna","award":["RFO21"],"award-info":[{"award-number":["RFO21"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Opioids are the most effective drugs used for the management of moderate to severe pain; however, their chronic use is often associated with numerous adverse effects. Some results indicate the involvement of oxidative stress as well as of proteasome function in the development of some opioid-related side effects including analgesic tolerance, opioid-induced hyperalgesia (OIH) and dependence. Based on the evidence, this study investigated the impact of morphine, buprenorphine or tapentadol on intracellular reactive oxygen species levels (ROS), superoxide dismutase activity\/gene expression, as well as \u03b22 and \u03b25 subunit proteasome activity\/biosynthesis in SH-SY5Y cells. Results showed that tested opioids differently altered ROS production and SOD activity\/biosynthesis. Indeed, the increase in ROS production and the reduction in SOD function elicited by morphine were not shared by the other opioids. Moreover, tested drugs produced distinct changes in \u03b22(trypsin-like) and \u03b25(chymotrypsin-like) proteasome activity and biosynthesis. In fact, while prolonged morphine exposure significantly increased the proteolytic activity of both subunits and \u03b25 mRNA levels, buprenorphine and tapentadol either reduced or did not alter these parameters. These results, showing different actions of the selected opioid drugs on the investigated parameters, suggest that a low \u00b5 receptor intrinsic efficacy could be related to a smaller oxidative stress and proteasome activation and could be useful to shed more light on the role of the investigated cellular processes in the occurrence of these opioid drug side effects.<\/jats:p>","DOI":"10.3390\/molecules27238321","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T07:10:27Z","timestamp":1669792227000},"page":"8321","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Effects of Different Opioid Drugs on Oxidative Status and Proteasome Activity in SH-SY5Y Cells"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6146-1690","authenticated-orcid":false,"given":"Laura","family":"Rullo","sequence":"first","affiliation":[{"name":"Department of Pharmacy and Biotechnology, Alma Mater Studiorum\u2014University of Bologna, Via Irnerio 48, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca Felicia","family":"Caputi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology, Alma Mater Studiorum\u2014University of Bologna, Via Irnerio 48, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5365-3441","authenticated-orcid":false,"given":"Loredana Maria","family":"Losapio","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology, Alma Mater Studiorum\u2014University of Bologna, Via Irnerio 48, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4022-0900","authenticated-orcid":false,"given":"Camilla","family":"Morosini","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology, Alma Mater Studiorum\u2014University of Bologna, Via Irnerio 48, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6464-1961","authenticated-orcid":false,"given":"Luca","family":"Posa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Boston University, 700 Albany Street, Boston, MA 02118, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6378-1698","authenticated-orcid":false,"given":"Donatella","family":"Canistro","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology, Alma Mater Studiorum\u2014University of Bologna, Via Irnerio 48, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8734-0985","authenticated-orcid":false,"given":"Fabio","family":"Vivarelli","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology, Alma Mater Studiorum\u2014University of Bologna, Via Irnerio 48, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3610-2928","authenticated-orcid":false,"given":"Patrizia","family":"Romualdi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology, Alma Mater Studiorum\u2014University of Bologna, Via Irnerio 48, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8905-7393","authenticated-orcid":false,"given":"Sanzio","family":"Candeletti","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology, Alma Mater Studiorum\u2014University of Bologna, Via Irnerio 48, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1097\/j.pain.0000000000001384","article-title":"Chronic pain as a symptom or a disease: The IASP classification of chronic pain for the international classification of diseases (ICD-11)","volume":"160","author":"Treede","year":"2019","journal-title":"Pain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1007\/s40263-022-00924-2","article-title":"Current and future therapeutic options in pain management: Multi-mechanistic opioids involving both MOR and NOP receptor activation","volume":"36","author":"Coluzzi","year":"2022","journal-title":"CNS Drugs"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jpain.2005.08.001","article-title":"Opioid tolerance and hyperalgesia in chronic pain patients after one month of oral morphine therapy: A preliminary prospective study","volume":"7","author":"Chu","year":"2006","journal-title":"J. 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