Garlic oil polysulfides: H₂S- and O₂-independent prooxidants in buffer and antioxidants in cells

Abstract

The health benefits of garlic and other organosulfur-containing foods are well recognized and have been attributed to both prooxidant and antioxidant activities. The effects of garlic are surprisingly similar to those of hydrogen sulfide (H2S), which is also known to be released from garlic under certain conditions. However, recent evidence suggests that polysulfides, not H2S, may be the actual mediator of physiological signaling. In this study, we monitored formation of H2S and polysulfides from garlic oil in buffer and in human embryonic kidney (HEK) 293 cells with fluorescent dyes, 7-azido-4-methylcoumarin and SSP4, respectively and redox activity with two redox indicators redox-sensitive green fluorescent protein (roGFP) and DCF. Our results show that H2S release from garlic oil in buffer requires other low-molecular-weight thiols, such as cysteine (Cys) or glutathione (GSH), whereas polysulfides are readily detected in garlic oil alone. Administration of garlic oil to cells rapidly increases intracellular polysulfide but has minimal effects on H2S unless Cys or GSH are also present in the extracellular medium. We also observed that garlic oil and diallyltrisulfide (DATS) potently oxidized roGFP in buffer but did not affect DCF. This appears to be a direct polysulfide-mediated oxidation that does not require a reactive oxygen species intermediate. Conversely, when applied to cells, garlic oil became a significant intracellular reductant independent of extracellular Cys or GSH. This suggests that intracellular metabolism and further processing of the sulfur moieties are necessary to confer antioxidant properties to garlic oil in vivo.

Inorganic Reactive Sulfur-Nitrogen Species: Intricate Release Mechanisms or Cacophony in Yellow, Blue and Red?

“…It is in agreement with results of DeLeon et al who, in an assay based on the H 2 S-sensitive fluorescent dye 7-azido-4-methylcoumarin (AzMC), demonstrated that garlic oil and DATS, when used independently, cannot release H 2 S [35]. Interestingly, normoxic and hypoxic conditions showed comparable effects on H 2 S-release from garlic oil and DATS in the presence of Cys or GSH, jettisoning the idea of a crucial involvement of dioxygen.…”

The Effects of Different Garlic-Derived Allyl Sulfides on Anaerobic Sulfur Metabolism in the Mouse Kidney

“…In the aforementioned studies by Benavides et al [38], the real-time in vitro measurement of the H 2 S level was reported. Moreover, a recent study of DeLeon et al monitoring the formation of H 2 S and polysulfides from garlic oil in human embryonic kidney cells (HEK 293) revealed that administration of garlic oil to cells increased the intracellular polysulfide (sulfane sulfur) level but had a minimal effect on the H 2 S level [40]. Only after the addition of exogenous thiols (Cys, GSH) to cell culture, an increase in the H 2 S level was observed.…”

Allium vegetables for possible future of cancer treatment

“…(De Martino, Filomeni, Aquilano, Ciriolo, & Rotilio, ), (DeLeon, Gao, Huang, & Olson, ; Ueda et al, ), (Y.‐L. Chu et al, )…”

“…For many years, they have been used to prevent and treat certain diseases such as diabetes, arthritis, colds and flu, cough, headache, hemorrhage, asthma, atherosclerosis, and inflammatory diseases (H. A. R. Suleria, Butt, Anjum, Arshad, & Khalid, 2013;Zeng et al, 2017). It has recently been noted that these vegetables, in addition to the conventional antibacterial, antifungal, antiviral, antiprotozoal, and antiworm effects, showed extensive in vitro and in vivo antiproliferative, antimotility, and cytotoxic potentials against cancer cells (Abdelrahman, Mahmoud, El-Sayed, Tanaka, & Tran, 2017; Chu et al, -Others antitumor effects (chelating irons, ↓p38 adhesion of tumor cells and metastasis, growth inhibition, cell cycle arrest, ↑ROS production and damaging to lipids and proteins, ↓MMP, antiangiogenesis, block cellular aging, hindering cellular division by expression of p38, ↓autophagy, ↓side effects of chemotherapy and radiotherapy, AMPK/ TSC2 expression and beclin-1 signaling pathways) (Thomson & Ali, 2003), (Saedi, Md Noor, Ismail, & Othman, 2014), (Oommen, Anto, Srinivas, & Karunagaran, 2004) (Grudzien & Rapak, 2018), (Ishikawa et al, 2006), (Lestari & Rifa'i, 2018) (Saud et al, 2016;Ziaei et al, 2015), (Hodge, Hodge, & Han, 2002), (Guan, Zhao, Xie, & Zeng, 2018) (Belloir, Singh, Daurat, Siess, & Le Bon, 2006), (Knowles & Milner, 2003) (De Martino, Filomeni, Aquilano, Ciriolo, & Rotilio, 2006), (DeLeon, Gao, Huang, & Olson, 2016;Ueda et al, 2002), (Y.-L. Chu et al, 2013) (Belloir et al, 2006), (Yamazaki et al, 1992) (Saud et al, 2016;Ziaei et al, 2015), (Hodge et al, 2002) , (H.-S. Chang et al, 2012), (Sowjanya, Devi, & Madhavi, 2009;Upadhyay, 2017), (Lin et al, 2017), (Y.-L. …”