{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T08:12:23Z","timestamp":1773821543187,"version":"3.50.1"},"reference-count":44,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bulgarian Ministry of Education and Science under the National Program for Research \u201cYoung Scientists and Postdoctoral Students 2021\u201d"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Oxidative stress is one of the key factors responsible for many diseases\u2013neurodegenerative (Parkinson and Alzheimer) diseases, diabetes, atherosclerosis, etc. Creatine, a natural amino acid derivative, is capable of exerting mild, direct antioxidant activity in cultured mammalian cells acutely injured with an array of different reactive oxygen species (ROS) generating compounds. The aim of the study was in vitro (on isolated rat brain sub-cellular fractions\u2013synaptosomes, mitochondria and microsomes) evaluation of newly synthetized creatine derivatives for possible antioxidant and neuroprotective activity. The synaptosomes and mitochondria were obtained by multiple centrifugations with Percoll, while microsomes\u2013only by multiple centrifugations. Varying models of oxidative stress were used to study the possible antioxidant and neuroprotective effects of the respective compounds: on synaptosomes\u20136-hydroxydopamine; on mitochondria\u2013tert-butyl hydroperoxide; and on microsomes\u2013iron\/ascorbate (non-enzyme-induced lipid peroxidation). Administered alone, creatine derivatives and creatine (at concentration 38 \u00b5M) revealed neurotoxic and pro-oxidant effects on isolated rat brain subcellular fractions (synaptosomes, mitochondria and microsomes). In models of 6-hydroxydopamine (on synaptosomes), tert-butyl hydroperoxide (on mitochondria) and iron\/ascorbate (on microsomes)-induced oxidative stress, the derivatives showed neuroprotective and antioxidant effects. These effects may be due to the preservation of the reduced glutathione level, ROS scavenging and membranes\u2019 stabilizers against free radicals. Thus, they play a role in the antioxidative defense system and have a promising potential as therapeutic neuroprotective agents for the treatment of neurodegenerative disorders, connected with oxidative stress, such as Parkinson\u2019s disease.<\/jats:p>","DOI":"10.3390\/life13010139","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T05:02:30Z","timestamp":1672808550000},"page":"139","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Newly Synthesized Creatine Derivatives as Potential Neuroprotective and Antioxidant Agents on In Vitro Models of Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"13","author":[{"given":"Ivanka","family":"Kostadinova","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magdalena","family":"Kondeva-Burdina","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0509-6526","authenticated-orcid":false,"given":"Lyubomir","family":"Marinov","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lubomir L.","family":"Vezenkov","sequence":"additional","affiliation":[{"name":"Institut des Biomol\u00e9cules Max Mousseron (IBMM), CNRS, Universit\u00e9 de Montpellier, ENSCM, 226-234 Av. du Professeur Emile Jeanbrau, 34090 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4860-9053","authenticated-orcid":false,"given":"Rumyana","family":"Simeonova","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1002\/ana.410440704","article-title":"The early diagnosis of Parkinsons disease","volume":"44","author":"Brooks","year":"1998","journal-title":"Ann. 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