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.
Source: PubMed, NCBI / U.S. National Library of Medicine
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 HDLand HDL, characterized by association rate constants (K) of 14.78 and 6.20 μMs, dissociation rate constants (K) of 0.35 sand 0.22 s, and equilibrium dissociation constants () of 0.024 and 0.035 μM, respectively. In conclusion, CIGB-258 exerted a substantial im
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 HDLand HDL, characterized by association rate constants (K) of 14.78 and 6.20 μMs, dissociation rate constants (K) of 0.35 sand 0.22 s, and equilibrium dissociation constants () 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.