Table 3.
Redox biomarkers reported in non-auditory noise exposure studies focusing on the circulation and brain regions or other remote organs.
| Redox biomarker | Method of detection/quantificationa | Quality scoreb | Ref. |
|---|---|---|---|
| 3-Nitrotyrosine | Plasma and cardiac levels of 3-NT-positive proteins by dot blot analysis – also abolished in Nox2 knockout mice and only visible upon sleep phase noise. Additive increase by noise/AT-II infusion and suppression by HO-1/NRF-2 activation by hemin and DMF. Aortic levels of 3-NT-positive proteins by IHC with additive increase by noise/AT-II infusion. 3-NT levels increased in plasma of noise-exposed humans. | ++ | Plasma and heart [14,16,245,247,461]; Aorta [14,247,281,463]; Humans [16] |
| Malondialdehyde | Plasma and cardiac levels of MDA-positive proteins by dot blot analysis – also abolished in Nox2 knockout mice and only visible upon sleep phase noise and prevention by LysM+ cell ablation. Brain MDA levels increased in rats by noise by ELISA or by thiobarbituric acid assay. | + | Plasma [14,16,281]; Heart [245]; Rats [206]; Brain [571,574] |
| 4-Hydroxynonenal | Aortic levels of 4-HNE-positive proteins by IHC. Plasma levels of 4-HNE-positive proteins by dot blot analysis - diminished by HO-1/NRF-2 activation by hemin and DMF. | ++ | Aorta [14,463]; Plasma [247,461] |
| 8-Hydroxy-(deoxy)guanosine | Aortic levels of 8-OH-(d)G-positive DNA/RNA by IHC. | ++ | Aorta [463] |
| Lipid peroxides and lipids | 8-isoprostane levels increased in plasma of noise-exposed humans by ELISA. Decreased unsaturated fatty acids in plasma of mice by LC/MS analysis. Increased plasma protein carbonyls in rats after noise by DNPH derivatization and Western blot. | +++ | Plasma humans [16]; Plasma mice [363] and rats [205,574]; Brain rats [275] |
| eNOS S-glutathionylation and uncoupling | Aortic and cardiac eNOS S-glutathionylation by immunoprecipitation and Western blot analysis. Aortic eNOS uncoupling by endothelial DHE staining with or without l-NAME. Endothelial ROS (most likely O2•−) formation and eNOS S-glutathionylation higher in sleep phase versus awake phase noise exposure and additive increase by noise/AT-II infusion and prevention by LysM+ cell ablation. Acute vitamin administration improved impaired endothelial function measured by FMD in humans. | ++ | Aorta and heart [14,16,247,281]; Human [30,234] |
| nNOS uncoupling | Uncoupling of nNOS by phosphorylation of serine 847 b y Western blot analysis. Also cerebral ROS (most likely O2•−) detection by DHE staining was normalized by l-NAME or specific nNOS inhibitor ARL-17477. | + | Brain [16] |
| ROS detection by DHE staining | Aortic and cerebral ROS (most likely O2•−) formation by DHE staining. Signal lower in Nox2 knockout mice and additive increase by noise/AT-II infusion and prevention by LysM+ cell ablation. Cerebral mtROS (O2•− and H2O2) formation by mitochondria-targeted DHE (mitoSOX) staining increased by noise and not diminished in Nox2 knockout mice. Aortic and cerebral ROS (O2•− and H2O2) levels higher in sleep phase versus awake phase noise exposure – in brain diminished by NOX-2 inhibitor GSK2795039. Cerebral mtROS (O2•− and H2O2) formation by mitoSOX staining higher in sleep phase versus awake phase noise exposure. Aortic, cardiac and cerebral ROS (O2•− and H2O2) signals diminished by HO-1/NRF-2 activation by hemin and DMF. Retinal and mesenteric ROS (O2•− and H2O2) formation by DHE staining - prevention by LysM+ cell ablation. | + | Aorta and brain [15,16,245,247,248,281,461]; Heart [461]; Retinal/mesenteric microvessels [281] |
| Superoxide detection by HPLC | Aortic and cerebral superoxide formation by HPLC-based quantification of 2-hydroxyethidium. Signal lower in Nox2 knockout mice by trend (aorta) and significant (brain/cortex). Aortic and cerebral superoxide levels higher in sleep phase versus awake phase noise exposure. Aortic and cardiac mitochondrial superoxide formation by HPLC-based quantification of 2-hydroxyethidium and mito-HE. Additive increase by noise/AT-II infusion and prevention by LysM+ cell ablation and suppression by exercise, fasting and AICAR (AMPK activator). | +++ | Aorta and brain [16,245,567]; Aorta and cardiac mitochondria [245,247,248,281,567] |
| Oxidative burst | Whole blood leukocyte-dependent ROS (O2•− and H2O2) formation upon stimulation with phorbol ester dibutyrate or zymosan A by the luminol analog L-012-enhanced chemiluminescence. Signal abolished in Nox2 knockout mice and was aggravated in Ogg1 knockout mice with impaired repair capacity of 8-OH-(d)G lesions. Cell-specific ROS (O2•− and H2O2) by flow cytometry in different myelomonocytic cell subsets. | + | Blood [16,245,248,463] |
| NOX activation | Cardiac NOX activity by NADPH-dependent stimulation in membrane fractions using lucigenin-enhanced chemiluminescence. Phosphorylation of p47phox at serine 328 and of myristoylated alanine-rich C-kinase substrate (MARCKS) (also in lung), the substrate of protein kinase C, by Western blot analysis. | – | Heart [14]; Brain [16]; Lung [15] |
| Upregulation of NOX isoforms | Aortic, pulmonary and myelomonocytic NOX-2 upregulation by Western blot analysis and immunohistochemistry (IHC) or Nox2 mRNA by RT-PCR - prevention by LysM+ cell ablation. Upregulation of Nox1 mRNA in lung endothelial cells and of NOX-1 protein by trend in the lung. Cerebral upregulation of Nox1 mRNA only by sleep phase noise. | + | Aorta and LEC [14,245,247,281,463]; Brain [16]; Lung [15]; Aorta and PBMCs [248] |
| Nox2 deletion | Vascular functional impairment, inflammatory phenotype and metabolic parameters in response to noise normalized by the knockout. | ++ | [16,363] |
| Hmox1 upregulation | Upregulation of Hmox1 mRNA in lung endothelial cells. Upregulation of Hmox1 mRNA and HO-1 protein by trend in the heart but in contrast decreased bilirubin levels (by oxidative break-down?). | + | LEC [14]; Heart [461] |
| Diminished aortic •NO formation | Aortic •NO bioavailability was decreased as measured by electron paramagnetic resonance spectroscopy-based Fe(DETC)2 spin trapping. DETC means diethyldithiocarbamate. | + | Aorta [14] |
| Altered plasma nitrite levels | Plasma nitrite/nitrate increased by noise as measured by commercial kit (due to iNOS induction). Plasma nitrite diminished by trend in mice by noise as measured by HPLC-based assay - additive significant decrease by noise/AT-II infusion. | + | Rats [206]; Mice [245,247] |
| Altered levels of SODs | Plasma and cerebral SOD activity diminished by noise in rats by ELISA or nitroblue tetrazolium assay. Cardiac SOD2 expression diminished by Western blot analysis in mice. | + | Plasma [206,571,574]; Heart [247] |
| Downregulation of glutathione peroxidase 1 (GPx-1) and catalase and others | Downregulation of various antioxidant genes in aorta by RNA sequencing. Diminished expression of catalase mRNA in brain was abolished in Nox2 knockout mice. Cerebral downregulation of catalase mRNA only by sleep phase noise. Plasma GPx-1 upregulation by ELISA in workers with high noise exposure. Cerebral GPx activity diminished by commercial kit. | + | Aorta [14]; Brain [16,571]; Human plasma [227] |
| GSH levels | GSH levels decreased by noise. | ++ | Rats [275] |
| DNA damage | Blood DNA strand breaks by comet assay higher in workers with high noise exposure. peripheral blood mononuclear cell (PBMCs) 8-oxoguanine glycosylase (OGG-1)-sensitive DNA strand breaks by comet assay higher in noise-exposed humans. Serum DNA damage in rats by ELISA. Heart and adrenal gland DNA strand breaks by comet assay higher in rats after loud noise. | + | Human blood [227]; Human PBMCs [333]; Rat [380,605,606] |
| Decrease in ΔΨm | Impaired mitochondrial membrane potential by TMRM in noise-induced hearing loss. | – | Cochlea [607] |
a
If not stated redox biomarkers were detected in noise-exposed mice.
b
Quality scores, based on the recommended detection modalities (see 2.4.2.): +++, highly recommended/state-of-the-art; ++, recommended; +, of potential value, may lack the specificity and/or straightforward interpretation; –, not recommended if used alone.