Dietary melatonin attenuates chromium-induced lung injuryviaactivating the Sirt1/Pgc-1α/Nrf2 pathway

Abstract

Exposure to chromium (Cr) causes a number of respiratory diseases, including lung cancer and pulmonary fibrosis.

L-carnitine alleviated acute lung injuries induced by potassium dichromate in rats: involvement of Nrf2/HO-1 signaling pathway

“…In the present study, exposure to PD significantly inhibited Nrf2/Keap1/NQO1 expression in the lung tissues. Our findings are in accordance with previous study that showed involvement of Nrf2 pathway in chromium-induced lung injury [ 39 ]. PD disrupted the association of Nrf2/Keap1 in the nucleus and provokes ROS production that inversely correlated with Nrf2 expression and its target genes Ho-1 and detoxification gene NQO1 [ 40 ].…”

Lungs as target of COVID-19 infection: Protective common molecular mechanisms of vitamin D and melatonin as a new potential synergistic treatment

“…At the same time, this caused a rise in the expression of crucial antioxidant target genes and the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). These findings indicate that melatonin exerts anti-inflammatory, antioxidant, and antiapoptosis effects in the attenuation of lung injury provoked by chromium exposure through SIRT1/Pgc-1α/Nrf2 signaling pathway [80]. It has also been determined that melatonin was able to mitigate the lung damage induced by carbon tetrachloride by the elimination of free radicals, the increase in the antioxidant ability of pulmonary tissues, and the induction of an effective anti-inflammatory response [81].…”

The Role of Toxic Metals and Metalloids in Nrf2 Signaling

“…Nrf2 signaling has been found to be an important mechanism in controlling ROS-induced cytotoxicity of liver cells after the exposure of rats to a single dose of K 2 Cr 2 O 7 by activating antioxidant enzymes and protecting the hepatocytes [ 115 ]. In other studies, an even lower single dose of K 2 Cr 2 O 7 was found to decrease the expression of P-AMPK/AMPK and Nrf2 in rat heart, followed by oxidative stress, apoptosis, and release of inflammatory mediators [ 29 ], while the same dose administered longer not only caused a significant decrease in Nrf2 but also affected Sirt1, Pgc-1α, HO-1, and NQO1 expression in rat lungs [ 8 ]. Furthermore, by using the zebrafish model, Shaw et al (2019) demonstrated that even environmentally relevant Cr concentration may initiate the increase in Nrf2 on both the transcriptional and translational levels, as well as enhance its nuclear translocation [ 116 ].…”

“…Under physiological conditions, Nrf2 is located in the cytoplasm, bound to its negative regulator, Kelch-like ECH-associated protein 1 (Keap1), and is constantly primed for proteasomal degradation by the Cul3–Rbx1–E3 ubiquitin ligase complex prompted by the interaction between a single Nrf2 protein and a Keap1 homodimer [ 7 ]. Following stimulation-induced phosphorylation, Nrf2 is relieved from Keap1 negative regulation by two separate mechanisms [ 8 , 9 ]. The first mechanism, the so-called “canonical pathway”, includes the chemical modification of highly reactive cysteines present in Keap1 BTB and IVR domains, which form protein–protein crosslinks following reaction with electrophiles and lead to the disturbance of the Nrf2 interaction with the Cul3–Keap1 E3 ubiquitin ligase complex, causing decreased Nrf2 proteasomal degradation ( Figure 1 A) [ 10 , 11 ].…”

“…After the translocation into the nucleus, Nrf2 binds to the Maf proteins [ 8 , 9 ]. Nrf2–Maf heterodimers positively regulate the expression of numerous of detoxification and antioxidant genes that contain a cis-acting element in their promoter region, which is known as the antioxidant response element (ARE).…”