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Int J Physiol Pathophysiol Pharmacol. 2018 Jun 25;10(3):132-138. eCollection 2018.

The peptide glycyl-ʟ-histidyl-ʟ-lysine is an endogenous antioxidant in living organisms, possibly by diminishing hydroxyl and peroxyl radicals.

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Department of Physiological Chemistry, Osaka University of Pharmaceutical Sciences 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.


Despite evidence that tripeptide glycyl-ʟ-histidyl-ʟ-lysine (GHK) is an endogenous antioxidant, its mechanism and importance are not fully understood. In the present study, the ability of GHK to reduce levels of reactive oxygen species (ROS) in Caco-2 cells was evaluated by flow cytometry with the oxidation-sensitive fluorescent dye 2',7'-dichlorodihydrofluorescein diacetate. Further, types of ROS diminished by GHK were assessed by utilizing an electron spin resonance (ESR) spin-trapping technique. GHK reduced the tert-butyl hydroperoxide-induced increase in ROS levels in Caco-2 cells at concentrations of 10 µM or less. Experiments utilizing an ESR spin-trapping technique revealed that, among hydroxyl (·OH), superoxide (O2-·), and peroxyl (ROO·) radicals generated by respective chemical reaction systems, GHK diminished signals of both ·OH and ROO·, but not O2-·. Additionally, the GHK effect on the signal of ·OH was much stronger than those of other well-known antioxidative, endogenous peptides, carnosine and reduced glutathione. These results suggest that GHK can function as an endogenous antioxidant in living organisms, possibly by diminishing ·OH and ROO·.


Glycyl-ʟ-histidyl-ʟ-lysine; endogenous antioxidant; hydroxyl radical; oxidative stress; peroxyl radical


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