Table 1.
Compounds preventing DNA damages due to the stimulation of antioxidant and detoxification systems and transition metal chelation.
| Compounds | Mechanisms | References |
|---|---|---|
| Trace elements | ||
| Selenium | Reduction of the ROS production and MAD levels. Participation in the formation of antioxidant enzymes. Activation of antioxidant enzymes (GPx, TRXR, CAT, SOD, and others). Improvement of protein levels of NRF2, HO-1, NQO-1. Metal ion chelation by selenium nanoparticles. |
[139,140,141,142,143,144,145,146,147] |
| Zinc | Reduction of the ROS production (by NADPH oxidation inhibition). Formation of Cu/Zn SOD. Maintaining the antioxidant defense (including NRF2), improvement of the antioxidant profile. Recovery of the antioxidant enzyme activity (SOD, CAT, GPx). Protection against DNA damages induced by other trace element supplementation. Metallothionein modulation. |
[141,148,149,150,151,152,153,154,155] |
| Iron | Suppression of the mitochondrial respiratory deficiency phenotype and decreases oxidative stress. Activation of antioxidant pathways (CAT, SOD). |
[156,157,158,159] |
| Magnesium | Removing the excess ROS. Elevation of the activity of antioxidant enzymes. |
[160] |
| Manganese | Protecting against ROS and MDA. Maintaining antioxidant defense, including positive regulation of NRF2 and antioxidant enzymes. Formation and enhancement of MnSOD. |
[161,162] |
| Vitamins and their derivatives | ||
| Vitamin A (retinol) | Free radical scavenging. Improvement of the activity of NRF2, HO-1, NQO-1. |
[163,164,165] |
| Vitamin B3 (nicotinic acid, or niacin; nicotinamide; nicotinamide riboside) | The decrease in the ROS production, reduction of mitochondrial defects. Increase in the total antioxidant capacity. NRF2 activation. |
[166,167,168] |
| Vitamin B6 (pyridoxine, pyridoxamine, pyridoxal) | The decrease in ROS and lipid peroxide levels. Improvement of the antioxidant profile. Protection of DNA integrity against hyperglycemia. |
[169,170,171] |
| Vitamin B9 (folic acid, or folate) | The decrease in the free radical production and promotion of the activity of antioxidant enzymes. May be involved in DNA damage in the elderly. |
[172,173,174,175,176,177,178] |
| Vitamin B12 (cobalamin) | The decrease in the free radical production and promotion of the activity of antioxidant enzymes. | [174,176] |
| Vitamin C (ascorbic acid) | Free radical scavenging activity. ROS production and MDA levels decrease. Protects against genotoxic damage induced by endogenous nitrosation. Activation of antioxidant enzymes (CAT, SOD, and others) and an increase in the GSH level. |
[179,180,181,182,183,184] |
| Vitamin D3 | ROS production decrease. Activation of the NRF2 signaling and the expression of antioxidant enzymes. |
[185,186,187,188,189,190,191,192,193] |
| Vitamin E (α-, γ-, δ-tocopherols, tocotrienols) | ROS and RNS scavenging. Antioxidant activity, decrease in the MDA level. γ-Tocopherol converts nitrogen dioxide to nitric oxide. Stimulation of antioxidant enzymes and an increase in the GSH level. |
[164,194,195,196,197,198,199,200,201,202,203,204] |
| Coenzymes | ||
| Coenzyme Q10 | ROS scavenging and a decrease in ROS production. Increase in the total antioxidant capacity, improvement of antioxidant status. Increase in the activity of antioxidant enzymes and GSH levels. |
[205,206,207,208,209,210,211,212] |
| Glutathione | An electron source in enzymatic reactions as a part of antioxidant defense. Excessive ROS level suppression. It can directly intercept DNA radicals to prevent permanent DNA damage. It can inhibit the binding of potential DNA damaging agents with DNA preventing its cleavage. |
[136,213,214] |
| Amino acids and their derivatives | ||
| Trimethylglycine (betaine) | Enhancement of the total antioxidant capacity, the activity of antioxidant enzymes (SOD, CAT, GPx), an increase in the GSH content. | [215,216,217] |
| Carnosine | Prevention of oxidative stress and a decrease in ROS production. Free radical scavenging. Improving the antioxidant status. |
[218,219,220,221,222] |
| L-Carnitine | ROS and MDA production decrease. Increase in the total antioxidant capacity. NRF2 activation. Improvement of the production and activity of antioxidant enzymes (SOD1, CAT, GPX1, PDRX4, and others), as well as the GSH level. |
[223,224,225,226,227,228,229,230,231,232] |
| Histidine | Required for the maintenance of the ROS level, the activity of NRF2, and antioxidant enzymes (both deficiency and excess are harmful). Chelating divalent metal ions. |
[233,234] |
| N-Acetylcysteine | ROS, RNS, and MDA production decrease. Enhancement of the total antioxidant capacity. Involved in glutathione synthesis, which is a cofactor of several antioxidant enzymes. Increase in the NRF2 activity and levels of antioxidant enzymes (GPx, SOD, GST) and GSH. |
[173,218,219,235,236,237,238,239,240,241,242,243,244,245,246,247] |
| γ-Glutamylcysteine | Increases the activity of the antioxidant enzymes and total antioxidant capacity. | [248] |
| Polyphenols | ||
| Green tea polyphenols | ROS production decrease. Restore and stimulate the functioning of antioxidant enzymes (SOD, CAT, XO, PRDX6). |
[202,249,250,251,252] |
| Epigallocatechin gallate | Free radical scavenging activity, ROS, and MDA production decrease. Protection against genotoxic damage by endogenous nitrosation. NRF2 and antioxidant defense activation (or prevention of its impairment). Iron chelating. |
[253,254,255,256,257,258,259,260,261] |
| Epicatechin gallate | The decrease in ROS production, scavenging free radicals. Enhancement of the activities of antioxidant enzymes and the GSH level. |
[262,263,264,265] |
| Catechin | The decrease in the production of ROS and RNS. Stimulation of NRF2 signaling and antioxidant defense (GPx, GST). Modulation of phase 1 and 2 enzyme activities. |
[266,267,268,269,270,271,272] |
| Epicatechin | Free radical scavenging. Metal chelating. Recovery of the antioxidant status. Modulation of phase 1 and 2 enzyme activities. |
[265,268,271,273,274,275] |
| Theaflavin | Inhibition of the ROS and MDA generation. Activation of NRF2 and antioxidant defense enzymes (GPx, CAT, SOD). Modulation of the AKT/FOXO3a signaling. Suppression of cytochrome P450. |
[271,276,277,278,279] |
| Apigenin | Intercalation with DNA bases. Free radical scavenging. Reduction of the ROS, MDA levels, and myeloperoxidase activity. Increase and restore of the GSH, GST, SOD, CAT, GPx levels. |
[280,281,282,283,284] |
| Luteolin | Intercalation with DNA bases. Free radical scavenging. Enhancement of the NRF2 and HO-1 expression. Iron chelator. |
[285,286,287,288,289] |
| Chrysin | Restoration of the antioxidant status after genotoxic treatment. Iron chelator. |
[289,290,291,292] |
| Curcumin | Free radical scavenging. ROS and MDA production decrease. Increase in the total antioxidant capacity. Stimulation of the ARE/NRF2 signaling and antioxidant defense enzymes. |
[293,294,295,296,297,298,299,300] |
| Quercetin | Binding with DNA bases prevents their damage. ROS scavenging, decrease in ROS production. Increase in the total antioxidant capacity. Activation of the NRF2 signaling pathway, enzymatic and non-enzymatic antioxidants. Amelioration of hyperglycemia and nitrosative stress. Iron chelating. |
[258,268,301,302,303,304,305,306,307,308,309] |
| Rutin | Encircles and binds nucleotides preventing DNA damage. ROS scavenging. The decrease in ROS and MDA production. Stimulation of NRF2. Activation or restoration of antioxidant defense enzymes. |
[183,301,309,310,311,312,313,314,315,316] |
| Isoquercitrin | ROS and RNS scavenging activity. Restoration of the antioxidant defense. |
[310,317] |
| Hyperoside | ROS scavenging. MDA production decrease. SOD, CAT, GPx activation. |
[318,319] |
| Kaempferol | Intercalation with DNA bases. The decrease in ROS and MDA levels. Activation of NRF2 and SIRT1. Increase or restoration of the expression of antioxidant enzymes (SOD1, SOD2, CAT, GPx, GCLC) and the GSH level. Suppression of cytochrome P450. |
[286,320,321,322] |
| Myricetin | Binding with DNA bases prevents their damage. The decrease in ROS and MDA levels. |
[268,301,323,324,325] |
| Morin | Free radical scavenging. Decreases the ROS production and content, the level of nitrites. Stimulation of the NRF2, HO-1 activity, and antioxidant defense (SOD, CAT, GSH). Iron binding and oxidation. |
[326,327,328,329,330,331,332] |
| Fisetin | ROS scavenging and decrease in the ROS generation. Increase in GSH, GCLC levels. |
[333,334,335,336] |
| Naringenin | ROS production decrease. Improvement of the antioxidant defense. Suppression of cytochrome P450. |
[337,338,339,340,341] |
| Naringin | Decrease in ROS, NO, XO, MDA. Increases levels of antioxidant enzymes and GSH. |
[342,343,344,345,346,347] |
| Hesperidin | ROS, RNS, MDA production decrease. Increase in the total antioxidant capacity. Activation of antioxidant defense enzymes. |
[348,349,350,351,352,353,354] |
| Diosmin | ROS and RNS production decrease. Antioxidant status maintaining. Activation of antioxidant defense enzymes and GSH. |
[354,355,356] |
| Silymarin and flavonolignans (Silybin) |
ROS scavenging, decrease in the ROS generation. Activation of HO-1. Increase or restoration of the enzymatic and non-enzymatic antioxidant defense. Copper chelating agents. |
[357,358,359,360,361,362,363,364,365] |
| Genistein | Intercalation into DNA. ROS production decrease. Free radical scavenging, including nitric oxide or peroxynitrite scavenging activities. Increase in the total antioxidant capacity. Enhancement of the NRF2 and HO-1 expression. Prevention of the antioxidant defense impairment. Induction of the expression of metallothioneins. It can chelate metabolites of polycyclic aromatic hydrocarbons. |
[366,367,368,369,370,371,372,373,374,375,376] |
| Daidzein | Free radical scavenging, including nitric oxide or peroxynitrite scavenging activities. Increase in the total antioxidant capacity. Prevention of antioxidant defense impairment. |
[366,371,374,375] |
| Grape seed procyanidin and proanthocyanidins | The decrease in the ROS and MDA generation. Activation of NRF2 and HO-1. Stimulation of the expression of SOD, CAT, GPx, GCLC, NQO1, and the GSH level. Metal chelating. |
[377,378,379,380,381,382] |
| Pyrogallol | Antioxidant defense stimulation (total antioxidant capacity, GPx). | [383] |
| Pyrocatechol | Antioxidant defense stimulation (total antioxidant capacity, GPx). | [383] |
| Cyanidin | ROS generation and accumulation decrease. Inhibition of endogenous nitrosation. |
[384,385,386,387] |
| Cyanidin-3-O-glucoside | Intercalation into DNA. The decrease in the ROS generation. Increase in the expression of NRF2 and detoxifying defense enzymes. Modulation of the GSH system. Down-regulation of the cytochrome P450 expression. |
[388,389,390,391] |
| Pelargonidin | Inhibition of the ROS generation and endogenous nitrosation. NRF2 activation. Modulation of antioxidative and detoxification enzymes (particularly, HO-1, GST, GPx, SOD, NQO1). |
[387,392,393,394,395] |
| Delphinidin | Suppression of the ROS formation. Restoration and activation of antioxidant and phase 2 detoxification enzymes (particularly, HO-1, GST, NQO1). Xenobiotic detoxification. |
[396,397,398,399] |
| Honokiol | Suppression of the ROS production. Prevention of the inflammation-induced oxidative stress. |
[400,401,402] |
| Sesamin | The decrease in the intracellular ROS and MDA production. NRF2 activation. Activation and restoration of antioxidant defense genes and enzymes (SOD, CAT, GSTD, GPx, and others), GSH level increase. |
[403,404,405,406,407,408] |
| Sesamol | High free radical scavenging activity. The decrease in intracellular ROS production. Activation and restoration of antioxidant defense genes and enzymes (SOD, CAT, GSTD, GPx, and others), GSH level increase. |
[403,409,410,411,412] |
| Resveratrol | Free radical scavenging activity. Recovering the nucleotide from its radical. ROS production decrease. NRF2 activation. Increases the enzymatic and non-enzymatic antioxidants status. Suppression of cytochrome P450. |
[185,257,413,414,415,416,417,418,419] |
| Polydatin (piceid) | Free radical scavenging, inhibition of oxidative stress. Enhances the antioxidant defense. |
[420,421,422,423,424] |
| Caffeic acid and its esters | Inhibition of the ROS generation and xanthine oxidase activity Free radical scavenging. Total antioxidant activity increase, NRF2 activation. Recovery of the GHS content and the activity of antioxidant enzymes. Iron chelating. |
[303,309,425,426,427,428,429,430,431,432,433] |
| Chlorogenic acid | Free radical scavenging activity. The decrease in ROS production. Protection against the genotoxic damage by endogenous nitrosation. Improves the expressions of NRF2, HO-1, SOD, GSH. Iron chelating. |
[253,433,434,435,436] |
| Rosmarinic acid | Encircling and binding nucleotides to prevent DNA damage. ROS scavenging, MDA decrease. Increase in the total antioxidant activity. Increase in the NRF2 activity and the expression of antioxidant and phase 2 detoxification enzymes, GSH level. Iron chelating. |
[303,428,433,437,438,439,440] |
| Cinnamic acid | Increase in the antioxidant capacity. Stimulation of the activity of antioxidant enzymes. Iron chelating. |
[431,441,442] |
| Coumaric acid | NRF2 activation. Stabilization of the antioxidant status. Blocking an increase in the xanthine oxidase activity. Iron chelating. |
[431,443,444,445] |
| Ferulic acid | Free radical scavenging activity. Protection against the genotoxic damage by endogenous nitrosation. Activation of NRF2 and antioxidant defense enzymes. Decrease in the inflammation-induced oxidative stress. Iron chelating. |
[253,309,431,433,446,447,448,449,450,451] |
| Salvianolic acid B | Improvement of the expressions of NRF2, HO-1, SOD, GSH. | [436] |
| Ellagic acid | ROS scavenging activity. Activation of NRF2, antioxidant, and phase 2 detoxification enzymes, GSH level increase. Reduction of the expression of cytochrome P450. |
[452,453,454,455,456,457] |
| Gallic acid | Free radical scavenging activity. Protection against the genotoxic damage by endogenous nitrosation. Stimulation of the activity of antioxidant enzymes and an increase in the GSH level. |
[253,458,459] |
| Vanillic acid | Free radical scavenging. Increase in the antioxidant capacity. Iron chelating. |
[433,441] |
| Tannins | Iron and copper chelators. Free radical scavenging activity. Reversion of the ROS production. Stimulation of antioxidant enzymes. |
[460,461,462,463,464,465,466] |
| Xanthohumol | ROS scavenging and improvement of the redox status. Activation of the NRF2 signaling. Induction of the glutathione related detoxification and the level of quinone reductase. The decrease in iron accumulation. |
[467,468,469,470,471] |
| Rambutan peel phenolics | High iron and copper chelating activities. The decrease in the production of hydroxyl radical and nitric oxide. |
[472] |
| Terpenes and terpenoids | ||
| Safranal | Protection against genotoxicants. The decrease in ROS, MDA, NO levels. Improvement of the redox status. Activation of the ARE/NRF2 signaling. Improvement of the antioxidant defense, including the activity of SOD, CAT, and the GSH level. |
[473,474,475,476] |
| Limonene | Antioxidant activity. The decrease in the MDA level. Activation of antioxidant enzymes (SOD, CAT, GPx) and GSH increasing. |
[477,478,479] |
| Thymol | Antioxidant activity. Free radical scavenging. The decrease in ROS and MDA levels. Prevention of the decrease in SOD, CAT, GSH levels. |
[480,481,482,483,484,485] |
| Carvacrol | Free radical scavenging. NRF2 activation. Increase in levels of GSH, GPx, SOD, CAT. Increase in metallothionein. |
[481,483,486,487,488,489] |
| Geraniol | Protects against methylating DNA damage. Activation of SOD, CAT, GPx, GST, QR, increase in the GSH level. The decrease in the cytochrome P450 activity. |
[480,490,491] |
| β-Caryophyllene | Decrease in oxidative and nitrative stresses. Activation of antioxidant enzymes. Antioxidant activity mediated by cannabinoid type-2 receptor activation. |
[492,493,494,495] |
| Borneol | Iron chelating. Increase in the GSH level. |
[483,496] |
| Ursolic acid | Free radical scavenging. The decrease in the ROS and RNS generation. Increase in the total antioxidant capacity. NRF2 activation. Improvement of the enzymatic and non-enzymatic antioxidant status. |
[497,498,499,500,501] |
| Oleanolic acid | The decrease in the ROS, NO, MDA levels. Stimulation of antioxidant enzymes (SOD, CAT, GPx, GR) and an increase in the GSH level. |
[502,503] |
| Lupeol | Reducing the ROS and MDA production. Prevention of DNA alkylation. Induction and restoration of the activity of antioxidant enzymes (SOD, CAT, GSH). |
[504,505,506,507] |
| Ginsenosides | ROS scavenging. Reducing the ROS, NO, and MDA levels, ROS absorption. Improvement of the total antioxidant capacity. NRF2 activation. Activation of antioxidant and phase 2 detoxification enzymes (SOD, GPx, NQO1), GSH level increasing. |
[508,509,510,511,512,513] |
| Gypenosides | Inhibition of the ROS production. Increase in the antioxidant enzyme activity (GST, GPx) and the GSH level. |
[514,515,516,517] |
| Glycyrrhetinic acid | The decrease in the ROS generation. NRF2 activation. |
[518,519] |
| Glycyrrhizic acid | Free radical scavenging. Reduction of ROS production. Restoration of levels of antioxidant enzymes and GSH. |
[520,521,522] |
| Astaxanthin | ROS scavenging activity. Prevention of the mitochondrial dysfunction. The decrease in ROS and MDA production. Increase in the total antioxidant capacity. Activation of NRF2 and antioxidant enzymes (SOD1, SOD2), increase in the GSH level. Reduction of the expression of cytochrome P450. |
[523,524,525,526,527,528] |
| Fucoxanthin | ROS scavenging activity. The decrease in the ROS level. Recovery of antioxidative enzymes and the GSH levels. |
[529,530,531,532] |
| Zeaxanthin | ROS scavenging activity. The decrease in ROS, RNS, and MDA levels. Recovery and increase in the expression of antioxidant enzymes (SOD, CAT, GPx) and the GSH level. |
[203,523,533,534,535] |
| Lutein | ROS scavenging activity. The decrease in ROS, RNS, and MDA levels. Influence on the expression of antioxidant defense genes, especially genes of oxygen transporters. Increase in the GSH level. |
[203,523,535,536,537,538] |
| Lycopene | Reduction of ROS, NO, and MDA levels. Activation of the NRF2 and HO-1 pathways. Antioxidant enzymatic and non-enzymatic defense stimulation. |
[539,540,541,542,543,544,545,546,547] |
| Bixin | NRF2 activator. Increase in the GSH level. |
[548,549,550] |
| Crocin | Protection against genotoxicants. The decrease in ROS, MDA, NO levels. Increase in the total antioxidant capacity. Stimulation of SOD, CAT. |
[473,551,552] |
| Organic acids | ||
| α-Lipoic acid | ROS and MDA production decrease. Stimulation of enzymatic and non-enzymatic antioxidant defense, as well as the NRF2/ARE/ERE signaling. It can inhibit the binding of potential damaging agents with DNA preventing its cleavage. Iron chelating. |
[136,208,228,257,258,553,554,555,556] |
| Isothiocyanates | ||
| Sulforaphane | Activator of NRF2/ARE and HO-1. Restoration of levels of antioxidant and phase 2 detoxification enzymes, GSH level increase. Decrease in glucose metabolism and the level of associated enzymes. |
[417,557,558,559,560,561,562,563,564,565,566] |
| Raphasatin | In low doses, it demonstrates anti-genotoxic and antioxidant activities. | [557,567] |
| Polyamines | ||
| Spermine | Free radical scavenging. | [568,569] |
| Alkaloids | ||
| Berberine | Free radical scavenging activity. Reduction of ROS, RNS, and MDA levels. Improvement of the total antioxidant capacity. Stimulation of the NRF2/HO-1 pathway, the expression of antioxidant enzymes and genes, increase in the GSH level. |
[185,570,571,572,573,574,575,576] |
| Indoles | ||
| 3,3′-Diindolylmethane | The decrease in ROS and MDA levels. Activation of NRF2/ARE. Increase in the expression of HO-1, NQO1, GST, and the GSH level. |
[577,578,579,580] |
| Other phytochemicals | ||
| Vanillin and its derivatives | Free radical scavenging. The decrease in ROS and MDA levels. Modulation of enzymatic and non-enzymatic antioxidant defense. |
[581,582,583,584,585] |
| Fucoidan | The decrease in the ROS level. Stimulation of NRF2, HO-1, and antioxidant defense enzymes. Metal ion chelating. |
[586,587,588] |
| Eugenol and isoeugenol | ROS scavenging. The decrease in the ROS and MDA production, block the DNA oxidation. Improvement of the antioxidant status. Activation and decline prevention of antioxidant enzymes (SOD, CAT) and GSH. The decrease in the cytochrome P450 activity. |
[483,589,590,591,592,593] |
| Chlorophyllin | The decrease in ROS and MDA levels. Activation NRF2 and antioxidant enzymes, increase in the GSH level. Reduction of the expression of cytochrome P450. Prevention of DNA fragmentation by poliovirus. |
[455,594,595] |
| Theaphenon-E | Activation NRF2 and antioxidant enzymes. Reduction of the expression of cytochrome P450. |
[455] |
| Hormones | ||
| Melatonin | Free radical scavenging. The decrease in ROS and MDA levels. Increase in the total antioxidant capacity. NRF2 activation. Enhancement of the activity of antioxidant and phase 2 detoxification enzymes (GPx, SOD, CAT, HO-1, NQO1) and the GSH level. Copper chelating agent. |
[257,596,597,598,599,600,601,602,603,604] |
| 17β-Estradiol | Intercalation into DNA. The decrease in ROS and MDA production. Modulation of enzymatic and non-enzymatic antioxidant systems. |
[246,367,605] |
| Raloxifene | ROS production decrease. Modulation of enzymatic and non-enzymatic antioxidant systems. |
[605] |
| Tamoxifen | ROS production decrease. Modulation of enzymatic and non-enzymatic antioxidant systems. |
[605] |
| Synthetic compounds | ||
| Metformin | ROS production inhibition due to AMPK activation. Modulation of NRF2 and antioxidant enzymes. Reduction of the expression of cytochrome P450. |
[185,606,607,608,609,610,611] |
| Rapamycin | Intracellular ROS production decrease. Modulation of intracellular antioxidants. |
[185,612,613] |
| Aspirin and bis(aspirinato)zinc(II) | Free radical scavenging. The decrease in intracellular ROS production. Increase in SOD, CAT, GPx levels. |
[185,614,615,616] |
| Alpha phenyl-tert-butyl nitrone and its derivatives | Free radical scavenging activity. The decrease in ROS production. |
[182,617,618,619,620,621] |
| 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) | Scavenging of DNA radicals. | [235] |
| Trolox | Decrease in ROS and RNS levels. Maintaining the antioxidant status. |
[235,622,623,624] |
| Rosuvastatin | Decrease in ROS and RNS levels. Maintaining the antioxidant status. |
[235] |
| Valproic acid | Decrease in the ROS and MDA production. Stimulates the Nrf2/HO-1 pathway and the expression of antioxidant enzymes. But can induce DNA damages. |
[625,626] |
| RG108 | Decrease in the ROS and MDA production. Stimulation of the expression of NRF2 and antioxidant enzymes. |
[626] |
| Ethylenediaminetetraacetic acid (EDTA) | Chelating of bivalent metals and radionuclides. Decrease in ROS and MDA levels. Maintaining the antioxidant status. |
[169,426,627,628,629] |
| Deferoxamine (Desferal) | Iron chelator. It can act as an antioxidant in stress conditions. But can influence the DNA damage response mechanism, particularly, by inhibition of PARP. |
[245,258,630,631] |
| Bathocuproine disulfonate | Copper chelating agent. | [604] |