ABSTRACT
Paraquat (PQ) is a toxic herbicide to humans. Once absorbed, it accumulates in the lungs. PQ has been well documented that the generation of reactive oxygen species (ROS) is the main mechanism of its toxicity. Oxidative damage of PQ in lungs is represented as generation of cytotoxic and fibrotic mediators, interruption of epithelial and endothelial barriers, and inflammatory cell infiltration. No effective treatment for PQ toxicity is currently available. Several studies have shown that natural compounds (NCs) have the potential to alleviate PQ-induced pulmonary toxicity, due to their antioxidant and anti-inflammatory effects. NCs function as protective agents through stimulation of nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathways. Elevation of Nrf2 levels leads to the expression of its downstream enzymes such as SOD, CAT, and HO-1. The hypothesized role of the Nrf2/ARE signaling pathway as the protective mechanism of NCs against PQ-induced pulmonary toxicity is reviewed.
Abbreviations
ARE | = | Antioxidant response element |
Keap1 | = | Kelch-like ECH-associated protein 1 |
GST | = | Glutathione S-transferase |
NQO1 | = | NAD(P)H quinone oxidoreductase 1 |
Nrf2 | = | Nuclear factor erythroid 2 (NFE2)-related factor 2 |
HO-1 | = | Heme oxygenase-1 |
GPx | = | Glutathione peroxidase |
XO | = | xanthine oxidase |
SOD | = | Superoxide dismutase |
NF-κB | = | Nuclear factor-κB |
NC | = | Natural compounds |
PQ | = | Paraquat |
TRX1 | = | Thioredoxin-1 |
NCs | = | Natural compounds |
TLRs | = | Toll like receptors |
PPAR-γ | = | Peroxisome proliferator-activated receptor-γ |
MAPKs | = | Mitogen-activated protein kinases |
CAT | = | Catalase |
PRDX3 | = | Peroxiredoxin 3 |
PRDX4 | = | Peroxiredoxin 4 |
Acknowledgment
The authors are thankful to the Clinical Toxicology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran, and Mashhad University of Medical Science, Mashhad, Iran.
Disclosure statement
No potential conflict of interest was reported by the authors.