Table 1.
Nrf2 signaling as a chemoprotection mechanism.
| Toxicity | Signaling Network | Compound | Nrf2 Expression | Outcomes | Refs |
|---|---|---|---|---|---|
| Cardiotoxicity | MiRNA-140-5p/Nrf2 | – | Down-regulation | Deteriorating DOX-mediated cardiotoxicity Reducing expressions of NQO1 and HO-1 Enhancing oxidative stress level |
[140] |
|
Cardiotoxicity
Hepatotoxicity Renotoxicity |
– | Asiatic acid | Up-regulation | Reducing necrosis, congestion and hyaline degeneration in heart Decreasing leukocyte inflammation, necrosis, apoptosis and fatty change in liver Decreasing necrosis and inflammation in kidney Mediating these protective effects via Nrf2 induction |
[98] |
| Cardiotoxicity | Nrf2/HO-1 Nrf2/NQO1 Nrf2/GCL |
Pristimerin | Up-regulation | Increasing expressions of Nrf2 and its downstream targets HO-1, NQO1 and GCL Reducing oxidative stress and fibrosis |
[91] |
| Cardiotoxicity | Nrf2/HO-1 Nrf2/NQO1 |
Tert-butylhydroquinone | Up-regulation | Ameliorating cardiotoxicity via induction of Nrf2 and its downstream targets | [113] |
| Cardiotoxicity | Nrf2/HO-1 | b-LAPachone | Up-regulation | Triggering nuclear translocation of Nrf2 Enhancing expressions of HO-1 and antioxidant enzymes such as SOD, CAT and GPx |
[101] |
| Cardiotoxicity | Nrf2/HO-1 Nrf2/NQO1 |
Cardamonin | Up-regulation | Protecting cells against inflammation and oxidative stress Reducing oxidative stress, apoptosis, and inflammation Inducing Nrf2 signaling and its downstream targets HO-1 and NQO1 |
[105] |
| Cardiotoxicity | Nrf2/HO-1 | Curdione | Up-regulation | Alleviating oxidative stress Preventing ROS overgeneration and mediating mitochondrial dysfunction Triggering Nrf2/HO-1 axis as an antioxidant axis |
[102] |
| Cardiotoxicity | MAPK/Nrf2/ARE | Chitosan oligosaccharide | Up-regulation | Decreasing oxidative stress and apoptosis Stimulating MAPK and subsequent induction of Nrf2/ARE axis Reinforcing antioxidant defense system |
[112] |
| Cardiotoxicity | MiRNA-200a/Nrf2 | – | Up-regulation | Improving cardiomyocyte contractile function Reducing levels of cardiac troponin I Ameliorating oxidative stress, inflammation and apoptosis Inducing Nrf2 signaling |
[143] |
| Cardiotoxicity | Nrf2/ARE | 3,3′-diindolylmethane | Up-regulation | Suppressing apoptosis Improving histopathological profile Enhancing expressions of HO-1, NQO1 and GST Reducing Bax and caspase-3 expression |
[114] |
| Cardiotoxicity | Sirt1/AMPK/Nrf2 | Acacetin | Up-regulation | Alleviation of cardiomyopathy Enhancing cell viability Preventing ROS overgeneration Activation of Sirt1/AMPK to induce Nrf2 signaling Triggering cell defense system |
[170] |
| Cardiotoxicity | Nrf2/HO-1 | Genistein | Up-regulation | Inducing Nrf2/HO-1 axis Reducing ROS levels by its scavenging feature Reducing lipid peroxidation and DNA damage |
[171] |
| Cardiotoxicity | Nrf2/LC-3II/autophagy | – | Down-regulation | Reducing oxidative stress Activating autophagy as a protective mechanism via LC-3II up-regulation Nrf2 inhibition aggravates DOX-mediated cardiotoxicity via impairing autophagy and enhancing oxidative stress |
[144] |
| Cardiotoxicity | – | p-coumaric acid | Up-regulation | Enhancing cell survival Inhibiting apoptosis and oxidative stress Providing nuclear translocation of Nrf2 |
[118] |
| Cardiotoxicity | Nrf2/NQO1 | Tanshinone IIA | Up-regulation | Enhancing cell viability and morphological profile Reducing oxidative parameters Up-regulation of NQO1 |
[124] |
| Cardiotoxicity | ORM1/Nrf2 | – | Up-regulation | ORM1 is correlated with a decrease in oxidative stress and apoptosis Up-regulation of Nrf2 and its downstream target HO-1 |
[158] |
| Testicular toxicity | – | – | Down-regulation | Inducing apoptosis and oxidative stress in testis Reducing Nrf2 expression |
[149] |
| Nephrotoxicity | – | Thymoquinone | Up-regulation | Reducing malondialdehyde and lipid peroxidation levels Enhancing SOD and GST levels Preventing necrosis and oxidative stressActivation of Nrf2 and improving antioxidant defense system |
[119] |