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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Comparison of Anti-Acute Phase Effect of CIGB-258 and Its Wild-Type Peptide (E18-3) in a Hyperinflammatory and Acute Bleeding Model of Zebrafish: A Surface Plasmon Resonance Study to Compare Binding Affinity with High-Density Lipoproteins

by
Kyung-Hyun Cho
1,*,
Yunki Lee
1,
Sang Hyuk Lee
1,
Ashutosh Bahuguna
1,
Seung Hee Baek
1,
María del Carmen Domínguez-Horta
2 and
Gillian Martínez-Donato
2
1
Raydel HDL Research Institute, Medical Innovation Complex, Daegu 41061, Republic of Korea
2
Center for Genetic Engineering and Biotechnology, Ave 31, e/158 y 190, Playa, Havana 10600, Cuba
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2026, 27(10), 4516; https://doi.org/10.3390/ijms27104516
Submission received: 17 April 2026 / Revised: 13 May 2026 / Accepted: 15 May 2026 / Published: 18 May 2026
(This article belongs to the Special Issue Amino Acid and Sugar Metabolism in Disease)
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Abstract

The study compares the effects of the HSP60-derived mutated peptide (CIGB-258) and its wild-type peptide (E18-3) on preventing carboxymethyllysine (CML)- and ethanol (Et-OH)-induced hemorrhagic events and acute toxicity in zebrafish. The results suggest a 67% survivability and swimming recovery in CIGB-258-treated zebrafish compared to only 20% in the CML+Et-OH-treated group. No effect of E18-3 was noticed on CML+Et-OH-impaired zebrafish survivability and swimming ability. Similarly, no effect of E18-3 was noticed on the CML+Et-OH-disturbed blood oxidative and antioxidant variables. In contrast, CIGB-258 showed a notable 35% lower rate of oxidized contents, and 2.0-fold and 1.2-fold higher paraoxonase (PON) and ferric ion reduction activity (FRA), respectively, than in the E18-3 group. Also, the CML+Et-OH-induced dyslipidemia was substantially prevented by the CIGB-258, whereas no protective effect of E18-3 was noticed. Similarly, the CML+Et-OH-triggered hepatic inflammation, steatosis, kidney damage, severe gastrointestinal bleeding, and intestinal fibrosis were successfully mitigated by co-treatment with CIGB-258. Surface plasmon resonance analysis revealed a substantial binding affinity of CIGB-258 for HDL2 and HDL3, characterized by association rate constants (Ka) of 14.78 and 6.20 μM−1s−1, dissociation rate constants (Kd) of 0.35 s−1 and 0.22 s−1, and equilibrium dissociation constants (KD) of 0.024 and 0.035 μM, respectively. In conclusion, CIGB-258 exerted a substantial impact on CML+Et-OH-triggered adverse events, with high affinity for HDL, whereas E18-3 exposure remained unaffected and failed to produce any beneficial effects.
Keywords: binding affinity; carboxymethyllysine; CIGB-258 (Jusvinza®); ethanol; high-density lipoproteins; surface plasmon resonance (SPR); zebrafish binding affinity; carboxymethyllysine; CIGB-258 (Jusvinza®); ethanol; high-density lipoproteins; surface plasmon resonance (SPR); zebrafish
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MDPI and ACS Style

Cho, K.-H.; Lee, Y.; Lee, S.H.; Bahuguna, A.; Hee Baek, S.; Domínguez-Horta, M.d.C.; Martínez-Donato, G. Comparison of Anti-Acute Phase Effect of CIGB-258 and Its Wild-Type Peptide (E18-3) in a Hyperinflammatory and Acute Bleeding Model of Zebrafish: A Surface Plasmon Resonance Study to Compare Binding Affinity with High-Density Lipoproteins. Int. J. Mol. Sci. 2026, 27, 4516. https://doi.org/10.3390/ijms27104516

AMA Style

Cho K-H, Lee Y, Lee SH, Bahuguna A, Hee Baek S, Domínguez-Horta MdC, Martínez-Donato G. Comparison of Anti-Acute Phase Effect of CIGB-258 and Its Wild-Type Peptide (E18-3) in a Hyperinflammatory and Acute Bleeding Model of Zebrafish: A Surface Plasmon Resonance Study to Compare Binding Affinity with High-Density Lipoproteins. International Journal of Molecular Sciences. 2026; 27(10):4516. https://doi.org/10.3390/ijms27104516

Chicago/Turabian Style

Cho, Kyung-Hyun, Yunki Lee, Sang Hyuk Lee, Ashutosh Bahuguna, Seung Hee Baek, María del Carmen Domínguez-Horta, and Gillian Martínez-Donato. 2026. "Comparison of Anti-Acute Phase Effect of CIGB-258 and Its Wild-Type Peptide (E18-3) in a Hyperinflammatory and Acute Bleeding Model of Zebrafish: A Surface Plasmon Resonance Study to Compare Binding Affinity with High-Density Lipoproteins" International Journal of Molecular Sciences 27, no. 10: 4516. https://doi.org/10.3390/ijms27104516

APA Style

Cho, K.-H., Lee, Y., Lee, S. H., Bahuguna, A., Hee Baek, S., Domínguez-Horta, M. d. C., & Martínez-Donato, G. (2026). Comparison of Anti-Acute Phase Effect of CIGB-258 and Its Wild-Type Peptide (E18-3) in a Hyperinflammatory and Acute Bleeding Model of Zebrafish: A Surface Plasmon Resonance Study to Compare Binding Affinity with High-Density Lipoproteins. International Journal of Molecular Sciences, 27(10), 4516. https://doi.org/10.3390/ijms27104516

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