{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T21:15:22Z","timestamp":1783545322955,"version":"3.55.0"},"reference-count":64,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T00:00:00Z","timestamp":1724803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>CIGB-258 is known to exert anti-inflammatory activity via structural stabilization of apolipoprotein A-I (apoA-I) and functional enhancement of high-density lipoproteins (HDL) against acute toxicity of carboxymethyllysine (CML). The co-presence of CIGB-258 in reconstituted HDL (rHDL) formed larger rHDL particles and enhanced anti-inflammatory activity in a dose-dependent manner of apoA-I:CIGB-258, 1:0, 1:0.1, 1:0.5, and 1:1 of molar ratio, in the synthesis of the rHDL. However, no study has evaluated the enhancement of HDL functionality by the co-presence of lipid-free apoA-I and CIGB-258. The present study was therefore designed to compare the structural stabilization and functional improvement of HDL in the presence of lipid-free apoA-I and CIGB-258 in molar ratios of 1:0, 1:0.1, 1:0.5, and 1:1 within both HDL2 and HDL3. As the concentration of CIGB-258 increased, it effectively inhibited the cupric-ion-induced oxidation of HDL, thereby safeguarding apoA-I from proteolytic degradation. Additionally, the wound-healing activity of zebrafish was significantly (p &lt; 0.01) enhanced by the co-addition of apoA-I:CIGB-258 (1:1) up to 1.6-fold higher than apoA-I alone (1:0) under the presence of CML. ApoA-I:CIGB-258 (1:1) treatment exhibited the lowest apoptosis and production of reactive oxygen species against CML-induced damage in the wound site. Also, an increase in wounded tissue granulation and epidermis thickness was observed with increasing concentration of CIGB-258 during 48 h post-treatment via the healing process. Intraperitoneal injection of apoA-I:CIGB-258 mixture remarkably ameliorated the acute paralysis and restored zebrafish swimming ability impaired by the acute toxicity of CML. The increase of CIGB-258 content, especially co-injection of apoA-I:CIGB-258 (1:1), leads to a significant 2.3-fold (p &lt; 0.001) and 4.1-fold (p &lt; 0.001) higher zebrafish survivability and recovery of swimming ability, respectively, than those of CML-control. In the apoA-I:CIGB-258 (1:1) group, neutrophil infiltration and interleukin (IL)-6 production was lowest in the hepatic tissue with the least cellular damage and apoptosis. Additionally, the group treated with apoA-I:CIGB-258 (1:1) demonstrated the lowest plasma levels of total cholesterol (TC) and triglycerides (TG), along with minimal damage to the kidney, ovary, and testicular cells. Conclusively, co-treatment of CIGB-258 with apoA-I effectively mitigated acute inflammation in zebrafish, safeguarded vital organs, structurally stabilized apoA-I, and enhanced HDL functionality.<\/jats:p>","DOI":"10.3390\/antiox13091049","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T11:54:10Z","timestamp":1724846050000},"page":"1049","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Enhancing Wound Healing and Anti-Inflammatory Effects by Combination of CIGB-258 and Apolipoprotein A-I against Carboxymethyllysine Toxicity in Zebrafish: Insights into Structural Stabilization and Antioxidant Properties"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1198-4140","authenticated-orcid":false,"given":"Kyung-Hyun","family":"Cho","sequence":"first","affiliation":[{"name":"Raydel Research Institute, Medical Innovation Complex, Daegu 41061, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunki","family":"Lee","sequence":"additional","affiliation":[{"name":"Raydel Research Institute, Medical Innovation Complex, Daegu 41061, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Hyuk","family":"Lee","sequence":"additional","affiliation":[{"name":"Raydel Research Institute, Medical Innovation Complex, Daegu 41061, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Eun","family":"Kim","sequence":"additional","affiliation":[{"name":"Raydel Research Institute, Medical Innovation Complex, Daegu 41061, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashutosh","family":"Bahuguna","sequence":"additional","affiliation":[{"name":"Raydel Research Institute, Medical Innovation Complex, Daegu 41061, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria del Carmen","family":"Dominguez-Horta","sequence":"additional","affiliation":[{"name":"Center for Genetic Engineering and Biotechnology, Ave 31, e\/158 y 190, Playa, La Havana 10600, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian","family":"Martinez-Donato","sequence":"additional","affiliation":[{"name":"Center for Genetic Engineering and Biotechnology, Ave 31, e\/158 y 190, Playa, La Havana 10600, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Denimal, D. 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