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

被引:0
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作者
Cho, Kyung-Hyun [1 ]
Lee, Yunki [1 ]
Lee, Sang Hyuk [1 ]
Kim, Ji-Eun [1 ]
Bahuguna, Ashutosh [1 ]
Dominguez-Horta, Maria del Carmen [2 ]
Martinez-Donato, Gillian [2 ]
机构
[1] Med Innovat Complex, Raydel Res Inst, Daegu 41061, South Korea
[2] Ctr Genet Engn & Biotechnol, Ave 31 E-158 & 190, Playa 10600, La Havana, Cuba
关键词
apolipoprotein A-I (apoA-I); CIGB-258 (Jusvinza (R)); high-density lipoproteins (HDL); carboxymethyllysine (CML); zebrafish; interleukin-6; HIGH-DENSITY-LIPOPROTEINS; HUMAN HEAT-SHOCK-PROTEIN-60; ARTHRITIS; OXIDATION; PROTEIN; ATHEROSCLEROSIS; TORCETRAPIB; BINDING; SEPSIS; TARGET;
D O I
10.3390/antiox13091049
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 < 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 < 0.001) and 4.1-fold (p < 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.
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页数:28
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