{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T10:59:31Z","timestamp":1789037971653,"version":"build-2803163510"},"reference-count":66,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T00:00:00Z","timestamp":1681171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Inflammation and atherosclerosis are intimately associated via the production of dysfunctional high-density lipoproteins (HDL) and modification of apolipoprotein (apo) A-I. A putative interaction between CIGB-258 and apoA-I was investigated to provide mechanistic insight into the protection of HDL. The protective activity of CIGB-258 was tested in the CML-mediated glycation of apoA-I. The in vivo anti-inflammatory efficacy was compared in paralyzed hyperlipidemic zebrafish and its embryo in the presence of CML. Treatment of CML induced greater glycation extent of HDL\/apoA-I and proteolytic degradation of apoA-I. In the presence of CML, however, co-treatment of CIGB-258 inhibited the glycation of apoA-I and protected the degradation of apoA-I, exerting enhanced ferric ion reduction ability. Microinjection of CML (500 ng) into zebrafish embryos resulted in acute death with the lowest survivability with severe developmental defects with interleukin (IL)-6 production. Conversely, a co-injection of CIGB-258 or Tocilizumab produced the highest survivability with a normal development speed and morphology. In hyperlipidemic zebrafish, intraperitoneal injection of CML (500 \u03bcg) caused the complete loss of swimming ability and severe acute death with only 13% survivability 3 h post-injection. A co-injection of the CIGB-258 resulted in a 2.2-fold faster recovery of swimming ability than CML alone, with higher survivability of approximately 57%. These results suggest that CIGB-258 protected hyperlipidemic zebrafish from the acute neurotoxicity of CML. Histological analysis showed that the CIGB-258 group had 37% lower infiltration of neutrophils in hepatic tissue and 70% lower fatty liver changes than those of the CML-alone group. The CIGB-258 group exhibited the smallest IL-6 expression in the liver and the lowest blood triglyceride level. CIGB-258 displayed potent anti-inflammatory activity in hyperlipidemic zebrafish by inhibiting apoA-I glycation, promoting rapid recovery from the paralysis of CML toxicity and suppression of IL-6, and lowering fatty liver changes.<\/jats:p>","DOI":"10.3390\/ijms24087044","type":"journal-article","created":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T03:11:23Z","timestamp":1681182683000},"page":"7044","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["CIGB-258 Exerts Potent Anti-Inflammatory Activity against Carboxymethyllysine-Induced Acute Inflammation in Hyperlipidemic Zebrafish via the Protection of Apolipoprotein A-I"],"prefix":"10.3390","volume":"24","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"},{"name":"LipoLab, Yeungnam University, Gyeongsan 38541, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo-Seon","family":"Nam","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":"Hye-Jee","family":"Na","sequence":"additional","affiliation":[{"name":"Raydel Research Institute, Medical Innovation Complex, Daegu 41061, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"del Carmen Dominguez-Horta","sequence":"additional","affiliation":[{"name":"Center for Genetic Engineering and Biotechnology, Ave 31, e\/158 y 190, Playa, La Habana 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 Habana 10600, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,11]]},"reference":[{"key":"ref_1","unstructured":"Mak, T.W., and Saunders, M.E. 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