S-Nitrosothiols in Food and Biological Systems: Formation, Stability, and Functional Applications

Omca Demirkol; İnci Cerit; Özlem Aktürk Gümüşay

S-Nitrosothiols in Food and Biological Systems: Formation, Stability, and Functional Applications

Abstract

This comprehensive review explores the multifaceted roles and applications of S-nitrosothiols (RSNOs) in both biological and food systems. RSNOs are formed through the covalent bonding of nitric oxide (NO) to thiol-containing molecules, enabling them to act as NO reservoirs and redox modulators. In physiological systems, RSNOs are implicated in key signaling pathways, including vasodilation, immune response, and protein regulation via reversible S-nitrosation.

In food systems, RSNOs contribute as antioxidants and natural preservatives, formed especially under acidic conditions or during the use of NO-donors like sodium nitrite. These compounds help extend shelf life and preserve sensory qualities, while also offering potential health benefits via NO bioactivity in the gastrointestinal tract. Factors such as pH, light, temperature, and metal ion exposure significantly affect RSNOs stability. Their degradation pathways, mainly thermal and photolytic, release NO and reactive nitrogen species (RNS), which influence both physiological effects and food safety.

This review explicitly connects the biochemical and physiological roles of RSNOs as nitric oxide reservoirs and redox modulators with their formation pathways, stability determinants, and functional behavior in food systems, thereby integrating molecular mechanisms with food matrix dynamics. The review also outlines applications in meat and plant-based products, including enhanced color, flavor, antimicrobial properties, and fraud detection. RSNOs show promise in functional foods, nutraceuticals, and clean-label formulations due to their antioxidant and cardiovascular benefits. Despite their potential, safety and toxicity concerns—especially related to NO overproduction and oxidative stress—require careful dose regulation and further toxicological studies.

Keywords

S nitrosothiols (RSNOs), Nitric oxide (NO), Food processing effects, Redox reactions, Bioactive nitrogen species

References

K. Broniowska, A. Diers, and N. Hogg, “S-nitrosoglutathione,” Biochim. Biophys. Acta Gen. Subj., vol. 1830, no. 5, pp. 3173–3181, 2013, doi: 10.1016/j.bbagen.2013.02.004.
C. Massa et al., “Biological mechanisms of S-nitrosothiol formation and degradation: How is specificity of S-nitrosylation achieved?” Antioxidants, vol. 10, no. 7, Art. no. 1111, 2021, doi: 10.3390/antiox10071111.
E. Whalen et al., “Regulation of β-adrenergic receptor signaling by S-nitrosylation of G-protein-coupled receptor kinase 2,” Cell, vol. 129, no. 3, pp. 511–522, 2007, doi: 10.1016/j.cell.2007.02.046.
D. Jourd’heuil, F. Jourd’heuil, and M. Feelisch, “Oxidation and nitrosation of thiols at low micromolar exposure to nitric oxide,” J. Biol. Chem., vol. 278, no. 18, pp. 15720–15726, 2003, doi: 10.1074/jbc.M300203200.
N. M. Giles, S. Kumari, B. Gang, C. Yuen, E. Billaud, and G. I. Giles, “The molecular design of S-nitrosothiols as photodynamic agents for controlled nitric oxide release,” Chem. Biol. Drug Des., vol. 80, no. 3, pp. 471–478, 2012, doi: 10.1111/j.1747-0285.2012.01420.x.
L. C. Pinheiro et al., “Gastric S-nitrosothiol formation drives the antihypertensive effects of oral sodium nitrite and nitrate in a rat model of renovascular hypertension,” Free Radic. Biol. Med., vol. 87, pp. 252–262, 2015, doi: 10.1016/j.freeradbiomed.2015.06.038.
R. J. Singh, N. Hogg, J. Joseph, and B. Kalyanaraman, “Photosensitized decomposition of S-nitrosothiols and 2-methyl-2-nitrosopropane: Possible use for site-directed nitric oxide production,” FEBS Lett., vol. 360, no. 1, pp. 47–51, 1995, doi: 10.1016/0014-5793(95)00065-H.
M. G. Oliveira, S. Shishido, A. B. Seabra, and N. H. Morgon, “Thermal stability of primary S-nitrosothiols: Roles of autocatalysis and structural effects on the rate of nitric oxide release,” J. Phys. Chem. A, vol. 106, no. 38, pp. 8963–8970, 2002, doi: 10.1021/jp025756u.
N. J. Kettenhofen, K. Broniowska, Á. Keszler, Y. Zhang, and N. Hogg, “Proteomic methods for analysis of S-nitrosation,” J. Chromatogr. B, vol. 851, no. 1–2, pp. 152–159, 2007, doi: 10.1016/j.jchromb.2007.02.035.
R. Gogiraju et al., “Arginase-1 deletion in erythrocytes promotes vascular calcification via enhanced GSNOR (S-nitrosoglutathione reductase) expression and NO signaling in smooth muscle cells,” Arterioscler. Thromb. Vasc. Biol., vol. 42, no. 12, 2022, doi: 10.1161/ATVBAHA.122.318338.

K. Wolhuter and P. Eaton, “How widespread is stable protein S-nitrosylation as an end-effector of protein regulation?,” Free Radic. Biol. Med., vol. 109, pp. 156–166, 2017, doi: 10.1016/j.freeradbiomed.2017.02.013.
B. A. Maron, S. S. Tang, and J. Loscalzo, “S-nitrosothiols and the S-nitrosoproteome of the cardiovascular system,” Antioxid. Redox Signal., vol. 18, no. 3, pp. 270–287, 2013, doi: 10.1089/ars.2012.4744.
S. Priya, T. Kaviyarasan, and S. Berchmans, “Naked eye detection of nitric oxide release from nitrosothiols aided by gold nanoparticles,” Analyst, vol. 137, no. 7, pp. 1541–1547, 2012, doi: 10.1039/C2AN16182F.
Q. Wang et al., “Catalytic formation of nitric oxide mediated by Ti–Cu coatings provides multifunctional interfaces for cardiovascular applications,” Adv. Mater. Interfaces, vol. 5, no. 6, 2018, doi: 10.1002/admi.201701487.
M. Begley, C. Kerr, and C. Hill, “Exposure to bile influences biofilm formation by Listeria monocytogenes,” Gut Pathog., vol. 1, no. 1, Art. no. 11, 2009, doi: 10.1186/1757-4749-1-11.
F. Vilhena, A. Silva, and S. Louro, “Reductive nitrosylation of water-soluble iron porphyrins by S-nitroso-N-acetylpenicillamine: Rate constants and EPR characterization,” J. Inorg. Biochem., vol. 100, no. 11, pp. 1722–1729, 2006, doi: 10.1016/j.jinorgbio.2006.06.006.
I. Srianta, I. Kuswardani, S. Ristiarini, N. Kusumawati, L. Godelive, and I. Nugerahani, “Utilization of durian seed for Monascus fermentation and its application as a functional ingredient in yogurt,” Bioresour. Bioprocess., vol. 9, no. 1, 2022, doi: 10.1186/s40643-022-00619-y.
J. Bonetti et al., “Intestinal absorption of S-nitrosothiols: Permeability and transport mechanisms,” Biochem. Pharmacol., vol. 155, pp. 21–31, 2018, doi: 10.1016/j.bcp.2018.06.018.
H. Remini et al., “Recent advances on stability of anthocyanins,” RUDN J. Agron. Anim. Ind., vol. 13, no. 4, pp. 257–286, 2018, doi: 10.22363/2312-797x-2018-13-4-257-286.
S. Aleryani, E. Milo, Y. Rose, and P. Kostka, “Superoxide-mediated decomposition of biological S-nitrosothiols,” J. Biol. Chem., vol. 273, no. 11, pp. 6041–6045, 1998, doi: 10.1074/jbc.273.11.6041.
A. Doosti, P. G. Dehkordi, and E. Rahimi, “Molecular assay to fraud identification of meat products,” J. Food Sci. Technol., vol. 51, no. 1, pp. 148–152, 2011, doi: 10.1007/s13197-011-0456-3.
M. Feelisch et al., “Concomitant S-, N-, and heme-nitros(yl)ation in biological tissues and fluids: Implications for the fate of NO in vivo,” FASEB J., vol. 16, no. 13, pp. 1775–1785, 2002, doi: 10.1096/fj.02-0363com.
J. S. Stamler et al., “Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin,” Proc. Natl. Acad. Sci. U.S.A., vol. 89, no. 16, pp. 7674–7677, 1992, doi: 10.1073/pnas.89.16.7674.
O. Demirkol, C. Adams, and N. Ercal, “Biologically important thiols in various vegetables and fruits,” J. Agric. Food Chem., vol. 52, no. 26, pp. 8151–8154, 2004.
D. M. Cawthorn, H. A. Steinman, and L. C. Hoffman, “A high incidence of species substitution and mislabelling detected in meat products sold in South Africa,” Food Control, vol. 32, no. 2, pp. 440–449, 2013, doi: 10.1016/j.foodcont.2013.01.008.
M. T. Gladwin et al., “S-nitrosohemoglobin is unstable in the reductive erythrocyte environment and lacks O₂/NO-linked allosteric function,” J. Biol. Chem., vol. 277, no. 31, pp. 27818–27828, 2002, doi: 10.1074/jbc.M203236200.
C. von Bargen, J. Dojahn, D. Waidelich, H.-U. Humpf, and J. Brockmeyer, “New sensitive high-performance liquid chromatography–tandem mass spectrometry method for the detection of horse and pork in halal beef,” J. Agric. Food Chem., vol. 61, no. 49, pp. 11986–11994, 2013, doi: 10.1021/jf404121b.
M. Montowska, M. R. Alexander, G. A. Tucker, and D. A. Barrett, “Authentication of processed meat products by peptidomic analysis using rapid ambient mass spectrometry,” Food Chem., vol. 187, pp. 297–304, 2015, doi: 10.1016/j.foodchem.2015.04.078.
K. Takaki, N. Hayashi, D. Wang, and T. Ohshima, “High-voltage technologies for agriculture and food processing,” J. Phys. D: Appl. Phys., vol. 52, no. 47, Art. no. 473001, 2019, doi: 10.1088/1361-6463/ab2e2d.
M. M. Cantwell and C. T. Elliott, “Nitrates, nitrites and nitrosamines from processed meat intake and colorectal cancer risk,” J. Clin. Nutr. Diet., vol. 3, no. 4, 2017, doi: 10.4172/2472-1921.100062.
L. Zhong et al., “Development of a food composition database for assessing nitrate and nitrite intake from animal-based foods,” Mol. Nutr. Food Res., vol. 66, no. 1, 2021, doi: 10.1002/mnfr.202100272.
N. Stanišić, V. Kurčubić, S. Stajić, I. Tomasevic, and I. Tomašević, “Integration of dietary fibre for health benefits, improved structure, and nutritional value of meat products and plant-based meat alternatives,” Foods, vol. 14, no. 12, Art. no. 2090, 2025, doi: 10.3390/foods14122090.
Y. Higashi, K. Noma, M. Yoshizumi, and Y. Kihara, “Endothelial function and oxidative stress in cardiovascular diseases,” Circ. J., vol. 73, no. 3, pp. 411–418, 2009, doi: 10.1253/circj.CJ-08-1102.
R. Hu et al., “Living macrophage-delivered tetrapod PdH nanoenzyme for targeted atherosclerosis management by ROS scavenging, hydrogen anti-inflammation, and autophagy activation,” ACS Nano, vol. 16, no. 10, pp. 15959–15976, 2022, doi: 10.1021/acsnano.2c03422.
P. Song and M.-H. Zou, “Regulation of NAD(P)H oxidases by AMPK in cardiovascular systems,” Free Radic. Biol. Med., vol. 52, no. 9, pp. 1607–1619, 2012, doi: 10.1016/j.freeradbiomed.2012.01.025.
A. A. Zaky et al., “Bioactivities, applications, safety, and health benefits of bioactive peptides from food and by-products: A review,” Front. Nutr., vol. 8, 2022, doi: 10.3389/fnut.2021.815640.
M. Aspri, P. Papademas, and D. Tsaltas, “Review on non-dairy probiotics and their use in non-dairy based products,” Fermentation, vol. 6, no. 1, Art. no. 30, 2020, doi: 10.3390/fermentation6010030.
N. Singh, “Functional foods,” in Edited Book of Dietary Supplements and Nutraceuticals [According to Latest Syllabus of B. Pharm–VIII Semester of Pharmacy Council of India], IIP Series, vol. 4, Sep. 2024, pp. 155–178, doi:10.58532/nbennurdsch16.
S. Rafaqat et al., “A comprehensive review on the sources, stability, and health implications of bioactive compounds present in foods,” Int. J. Biosci. Res. (IJBR), vol. 3, no. 8, pp. 112–118, 2025, doi: 10.70749/ijbr.v3i8.2007.
A. Nazir et al., “Functional foods as the prospective therapeutic option in chronic diseases: A systemic review,” J. Plant Environ., vol. 3, no. 2, 2021, doi: 10.33687/jpe.003.02.3990.
C. Dimou, H. Karantonis, D. Skalkos, and A. Koutelidakis, “Valorization of fruits by-products to unconventional sources of additives, oil, biomolecules and innovative functional foods,” Curr. Pharm. Biotechnol., vol. 20, no. 10, pp. 776–786, 2019, doi: 10.2174/1389201020666190405181537.
K. Rockett, M. Awburn, B. Aggarwal, W. Cowden, and I. Clark, “In vivo induction of nitrite and nitrate by tumor necrosis factor, lymphotoxin, and interleukin-1: Possible roles in malaria,” Infect. Immun., vol. 60, no. 9, pp. 3725–3730, 1992, doi: 10.1128/iai.60.9.3725-3730.1992.
N. Weiss, Y. Zhang, S. Heydrick, C. Bierl, and J. Loscalzo, “Overexpression of cellular glutathione peroxidase rescues homocyst(e)ine-induced endothelial dysfunction,” Proc. Natl. Acad. Sci. U.S.A., vol. 98, no. 22, pp. 12503–12508, 2001, doi: 10.1073/pnas.231428998.
S. M. Andrabi, N. S. Sharma, A. Karan, S. S. Shahriar, B. Cordon, B. Ma, and J. Xie, “Nitric oxide: Physiological functions, delivery, and biomedical applications,” Adv. Sci., vol. 10, no. 30, Art. no. 2303259, 2023, doi: 10.1002/advs.202303259.
J. O. Lundberg and E. Weitzberg, “Nitric oxide signaling in health and disease,” Cell, vol. 185, no. 16, pp. 2853–2878, 2022, doi: 10.1016/j.cell.2022.06.010.
J. E. Freedman, B. Frei, G. N. Welch, and J. Loscalzo, “Glutathione peroxidase potentiates the inhibition of platelet function by S-nitrosothiols,” J. Clin. Invest., vol. 96, no. 1, pp. 394–400, 1995, doi: 10.1172/JCI118047.
C. Rodrigues and A. Gonçalves, “Estudos toxicológicos e segurança de medicamentos,” Rev. FT, vol. 29, no. 150, pp. 21–22, 2025, doi: 10.69849/revistaft/ni10202509301521.
V. Ciaravino, T. McCullough, and A. Dayan, “Pharmacokinetic and toxicology assessment of INTERCEPT (S-59 and UVA treated) platelets,” Hum. Exp. Toxicol., vol. 20, no. 10, pp. 533–550, 2001, doi: 10.1191/096032701718120319.
P. Balmer, H. Phillips, A. Maestre, F. McMonagle, and S. Phillips, “The effect of nitric oxide on the growth of Plasmodium falciparum, P. chabaudi and P. berghei in vitro,” Parasite Immunol., vol. 22, no. 2, pp. 97–106, 2000, doi: 10.1046/j.1365-3024.2000.00281.x.

Details

Primary Language

English

Subjects

Food Sciences (Other)

Journal Section

Review

Authors

Omca Demirkol ^*
0000-0002-6026-5997
Türkiye

İnci Cerit
0000-0002-3106-8951
Türkiye

Özlem Aktürk Gümüşay
0000-0001-9106-3151
Türkiye

Early Pub Date

March 14, 2026

Publication Date

March 14, 2026

Submission Date

January 9, 2026

Acceptance Date

February 23, 2026

Published in Issue

Year 2026 Volume: 1 Number: 1

IZ

https://izlik.org/JA25SP37ES

APA

Demirkol, O., Cerit, İ., & Gümüşay, Ö. A. (2026). S-Nitrosothiols in Food and Biological Systems: Formation, Stability, and Functional Applications. Food Science Insights, 1(1), 27-40. https://izlik.org/JA25SP37ES

AMA

1.Demirkol O, Cerit İ, Gümüşay ÖA. S-Nitrosothiols in Food and Biological Systems: Formation, Stability, and Functional Applications. Food Science Insights. 2026;1(1):27-40. https://izlik.org/JA25SP37ES

Chicago

Demirkol, Omca, İnci Cerit, and Özlem Aktürk Gümüşay. 2026. “S-Nitrosothiols in Food and Biological Systems: Formation, Stability, and Functional Applications”. Food Science Insights 1 (1): 27-40. https://izlik.org/JA25SP37ES.

EndNote

Demirkol O, Cerit İ, Gümüşay ÖA (April 1, 2026) S-Nitrosothiols in Food and Biological Systems: Formation, Stability, and Functional Applications. Food Science Insights 1 1 27–40.

IEEE

[1]O. Demirkol, İ. Cerit, and Ö. A. Gümüşay, “S-Nitrosothiols in Food and Biological Systems: Formation, Stability, and Functional Applications”, Food Science Insights, vol. 1, no. 1, pp. 27–40, Apr. 2026, [Online]. Available: https://izlik.org/JA25SP37ES

ISNAD

Demirkol, Omca - Cerit, İnci - Gümüşay, Özlem Aktürk. “S-Nitrosothiols in Food and Biological Systems: Formation, Stability, and Functional Applications”. Food Science Insights 1/1 (April 1, 2026): 27-40. https://izlik.org/JA25SP37ES.

JAMA

1.Demirkol O, Cerit İ, Gümüşay ÖA. S-Nitrosothiols in Food and Biological Systems: Formation, Stability, and Functional Applications. Food Science Insights. 2026;1:27–40.

MLA

Demirkol, Omca, et al. “S-Nitrosothiols in Food and Biological Systems: Formation, Stability, and Functional Applications”. Food Science Insights, vol. 1, no. 1, Apr. 2026, pp. 27-40, https://izlik.org/JA25SP37ES.

Vancouver

1.Omca Demirkol, İnci Cerit, Özlem Aktürk Gümüşay. S-Nitrosothiols in Food and Biological Systems: Formation, Stability, and Functional Applications. Food Science Insights [Internet]. 2026 Apr. 1;1(1):27-40. Available from: https://izlik.org/JA25SP37ES