Reaction targets of antioxidants in azo-initiator or lipid hydroperoxide induced lipid peroxidation

Abstract

Lipid peroxidation (LPO) is reported to be involved in the pathogenesis of several oxidative diseases, and several therapeutic approaches using antioxidants have been proposed. LPO is thought to progress via a complicated series of multistep reactions suggesting that the activity of each antioxidant may be different, and depends on the reacting molecules. Hence, in this study, we evaluated the inhibitory mechanisms of several antioxidants toward arachidonic acid (AA) peroxidation induced by the azo initiator 2,2’-azobis(2-amidinopropane) dihydrochloride (AAPH) or a lipid hydroperoxide, hydroperoxyoctadecadienoic acid (HpODE)/hemin. Edaravone, ferrostatin-1, TEMPO and trolox effectively inhibited the production of malondialdehyde (MDA) and several oxidised AAs generated in the AAPH-induced LPO because of their scavenging ability toward lipid peroxyl radicals. In contrast, ebselen and ferrostatin-1 showed strong antioxidative activity in the HpODE/hemin-induced peroxidation. Under this condition, ebselen and ferrostatin-1 were thought to reduce HpODE and its derived alkoxyl radicals to the corresponding lipid alcohols. In conclusion, we found that each antioxidant had different antioxidative activities that prevented the progression of LPO. We expect that these findings will contribute to the design of novel therapeutic strategies using an appropriate antioxidant targeted to each step of the development of oxidative stress diseases.

Keywords:

• Lipid peroxidation
• antioxidant
• lipid radical
• lipid hydroperoxide
• LC/MS/MS

Acknowledgments

The authors appreciate the technical support provided by the Research Support Center of the Graduate School of Medical Sciences, Kyushu University. The authors thank Renee Mosi, PhD, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

This work was supported in part by the AMED under AMED-CREST Grant [JP19gm0910013 to K. Y.] and JSPS under KAKENHI Grants [18K14884 to Y. M., 18K19405, and 17H03977 to K. Y.], Japan. This work was supported in part by the Platform Project for Supporting Drug Discovery and Life Science Research from the AMED.