Antioxidant action of persulfides and polysulfides against free radical-mediated lipid peroxidation

Abstract

Hydrogen sulfide, hydropersulfides, and hydropolysulfides have been revealed to play important physiological roles such as cell signaling and protection against oxidative stress, but the underlying mechanisms and dynamics of action remain elusive. It is generally accepted that these species act by two-electron redox mechanisms, while the involvement of one-electron redox chemistry has received less attention. In this study, the radical-scavenging activity of hydrogen persulfide, hydrogen polysulfides (HS_nH n = 2–4), and diallyl- or dialkyl-sulfides (RS_nR, n = 1–4) was measured. Furthermore, their antioxidant effects against free radical-mediated human plasma lipid peroxidation were assessed by measuring lipid hydroperoxides. It was found that disodium disulfide, trisulfide, and tetrasulfide acted as potent peroxyl radical scavengers, the rate constant for scavenging peroxyl radical being 3.5 × 10⁵, 4.0 × 10⁵, and 6.0 × 10⁵ M⁻¹ s⁻¹ in PBS pH 7.4 at 37 °C respectively and that they inhibited plasma lipid peroxidation efficiently, the efficacy is increased with the catenation number. Disodium tetrasulfide was 1.5 times as reactive as Trolox toward peroxyl radical and inhibited plasma lipid peroxidation more efficiently than ascorbate and Trolox. On the other hand, diallyl- and dialkyl-sulfides did not exert significant radical-scavenging activity, nor did they inhibit lipid peroxidation efficiently, except for diallyl tetrasulfide, which suppressed plasma lipid peroxidation, despite less significantly than disodium tetrasulfide. Collectively, this study shows that hydrogen persulfide and hydrogen polysulfides act as potent radical-scavenging antioxidants and that, in addition to two-electron redox mechanisms, one electron redox reaction may also play important role in the in vivo defense against deleterious oxidative stress.

Keywords:

• Antioxidant
• free radical
• lipid peroxidation
• persulfides
• polysulfides
• thiols

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported in part by JSPS KAKENHI [grant number 20H00488 and 21H05270 for YS, 21K20707 for TK, and 22H05579 for YM] and Japan Agency for Medical Research and Development [AMED, Grant Number 20ek0210144h0001 and BINDS for YS].