{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T02:49:04Z","timestamp":1788922144505,"version":"build-2803163510"},"reference-count":46,"publisher":"Walter de Gruyter GmbH","issue":"4","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:sc>l<\/jats:sc>\n                    -Met-enkephalin is a neuropeptide known to exert protective effects in various experimental models of autoimmune and inflammatory diseases. These effects are mediated through opioid receptors and can be abolished by the opioid receptor antagonist naltrexone. Investigation of peptide enantiomerism and the incorporation of d-amino acids are crucial for designing novel peptides with altered structural and biological properties compared with their native l-forms. Since no data are currently available on the properties or biological activity of the d-Met-enkephalin enantiomer, we evaluated its hepatoprotective potential in a mouse model of acetaminophen-induced hepatotoxicity. Male CBA mice were treated with d-Met-enkephalin, and hepatoprotection was assessed by measuring plasma alanine aminotransferase (ALT) and aspartate amino-transferase (AST) activities, along with histological liver necrosis scores. The peptide\u2019s secondary structure and antisense peptide binding were analysed using circular dichroism and fluorescence spectroscopy, respectively.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:sc>d<\/jats:sc>\n                    -Met-enkephalin demonstrated dose-dependent hepatoprotective effects within the range of 0.5\u201320 mg kg\u20131, with maximal protection observed at 5 mg kg\n                    <jats:sup>\u20131<\/jats:sup>\n                    , a dose comparable to that of the l-enantiomer (7.5 mg kg\n                    <jats:sup>\u20131<\/jats:sup>\n                    ). This preservation of biological activity may be attributed to the presence of the achiral amino acid glycine at positions 2 and 3, which maintains the functional conformation of the d-enantiomer. The role of opioid receptor involvement was further examined through direct receptor blockade using naltrexone and indirect inhibition with the antisense peptide IPPKY.\n                  <\/jats:p>","DOI":"10.2478\/acph-2025-0036","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T11:03:42Z","timestamp":1768302222000},"page":"659-672","source":"Crossref","is-referenced-by-count":1,"title":["Peptide chirality and opioid receptor modulation: Hepatoprotective effect of d-Met-enkephalin in acetaminophen-induced liver injury"],"prefix":"10.2478","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2621-8257","authenticated-orcid":false,"given":"Petra","family":"Tur\u010di\u0107","sequence":"first","affiliation":[{"name":"University of Zagreb Faculty of Pharmacy and Biochemistry , Department of Pharmacology Zagreb , Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roko","family":"Martini\u0107","sequence":"additional","affiliation":[{"name":"General and Veterans Hospital Knin Knin , Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7438-8090","authenticated-orcid":false,"given":"Nikola","family":"\u0160tambuk","sequence":"additional","affiliation":[{"name":"Ru\u0111er Bo\u0161kovi\u0107 Institute, Center for Nuclear Magnetic Resonance , Zagreb , Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4132-2295","authenticated-orcid":false,"given":"Tin","family":"Weitner","sequence":"additional","affiliation":[{"name":"University of Zagreb Faculty of Pharmacy and Biochemistry , Department of General and Inorganic Chemistry , Zagreb , Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1871-2827","authenticated-orcid":false,"given":"Mirna","family":"Mom\u010dilovi\u0107","sequence":"additional","affiliation":[{"name":"University Hospital Centre Zagreb , Zagreb , Croatia"},{"name":"University of Zagreb Faculty of Pharmacy and Biochemistry , Department of Pharmacology Zagreb , Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1266-3402","authenticated-orcid":false,"given":"Alenka","family":"Boban-Blagai\u0107","sequence":"additional","affiliation":[{"name":"University of Zagreb School of Medicine Department of Pharmacology , Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Kos","sequence":"additional","affiliation":[{"name":"University of Zagreb School of Medicine Institute of Pathology , Zagreb , Croatia"},{"name":"Clinical Hospital Center \u201cSestre milosrdnice\u201d Clinical Department of Pathology \u201cLjudevit Jurak\u201d , Zagreb , Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1095-4575","authenticated-orcid":false,"given":"Ranko","family":"Stojkovi\u0107","sequence":"additional","affiliation":[{"name":"Ru\u0111er Bo\u0161kovi\u0107 Institute, Division of Molecular Medicine , Zagreb , Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"2026062413321865487_j_acph-2025-0036_ref_001","doi-asserted-by":"crossref","unstructured":"M. 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