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.

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.