Noise-Induced Cochlear Damage Involves PPAR Down-Regulation through the Interplay between Oxidative Stress and Inflammation
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Drug Administration
2.3. Noise Exposure
2.4. Auditory Brainstem Responses (ABRs)
2.5. F-Actin Staining: Hair Cell Count
2.6. Hematoxylin and Eosin Staining: SGN Survival
2.7. Western Immunoblot Analysis
2.8. Immunofluorescence Analysis on Cochlear Samples
2.8.1. DHE Assay
2.8.2. PPARα and PPARγ Expression in the Cochlear Tissue
2.8.3. Activation of Inflammatory Markers
2.9. Statistical Analysis
3. Results
3.1. Noise Exposure Induced Functional and Morphological Cochlear Damage
3.2. Analysis of Cochlear PPARα and PPARγ Expression after Noise Exposure
3.3. Noise Induced Cochlear Inflammatory Response
3.4. The Effects of Q-Ter and Anakinra on PPAR Expression, Oxidative Damage and Inflammatory Processes
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
- Morgan, M.J.; Liu, Z. Crosstalk of Reactive Oxygen Species and NF-ΚB Signaling. Cell Res. 2011, 21, 103–115. [Google Scholar] [CrossRef] [Green Version]
- Collins, Y.; Chouchani, E.; James, A.M.; Menger, K.; Cochemé, H.M.; Murphy, M.P. Mitochondrial redox signalling at a glance. J. Cell Sci. 2012, 125, 801–806. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dunn, J.D.; Alvarez, L.A.; Zhang, X.; Soldati, T. Reactive oxygen species and mitochondria: A nexus of cellular homeostasis. Redox Biol. 2015, 6, 472–485. [Google Scholar] [CrossRef]
- Liu, T.; Zhang, L.; Joo, D.; Sun, S.-C. NF-ΚB Signaling in Inflammation. Signal. Transduct. Target. Ther. 2017, 2, e17023. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fujioka, M.; Kanzaki, S.; Okano, H.J.; Masuda, M.; Ogawa, K.; Okano, H. Proinflammatory cytokines expression in noise-induced damaged cochlea. J. Neurosci. Res. 2006, 83, 575–583. [Google Scholar] [CrossRef] [Green Version]
- Yamamoto, H.; Omelchenko, I.; Shi, X.; Nuttall, A.L. The Influence of NF-KappaB Signal-Transduction Pathways on the Murine Inner Ear by Acoustic Overstimulation. J. Neurosci. Res. 2009, 87, 1832–1840. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- He, W.; Yu, J.; Sun, Y.; Kong, W. Macrophages in Noise-Exposed Cochlea: Changes, Regulation and the Potential Role. Aging Dis. 2020, 11, 191–199. [Google Scholar] [CrossRef] [Green Version]
- Tan, W.J.T.; Thorne, P.; Vlajkovic, S.M. Characterisation of cochlear inflammation in mice following acute and chronic noise exposure. Histochem. Cell Biol. 2016, 146, 219–230. [Google Scholar] [CrossRef]
- Rybak, L.P.; Whitworth, C.A.; Mukherjea, D.; Ramkumar, V. Mechanisms of cisplatin-induced ototoxicity and prevention. Hear. Res. 2007, 226, 157–167. [Google Scholar] [CrossRef]
- Fetoni, A.R.; Paciello, F.; Rolesi, R.; Pisani, A.; Moleti, A.; Sisto, R.; Troiani, D.; Paludetti, G.; Grassi, C. Styrene targets sensory and neural cochlear function through the crossroad between oxidative stress and inflammation. Free Radic. Biol. Med. 2021, 163, 31–42. [Google Scholar] [CrossRef]
- Fujimoto, C.; Yamasoba, T. Oxidative Stresses and Mitochondrial Dysfunction in Age-Related Hearing Loss. Oxidative Med. Cell. Longev. 2014, 2014, 1–6. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fetoni, A.R.; De Bartolo, P.; Eramo, S.L.M.; Rolesi, R.; Paciello, F.; Bergamini, C.; Fato, R.; Paludetti, G.; Petrosini, L.; Troiani, D. Noise-Induced Hearing Loss (NIHL) as a Target of Oxidative Stress-Mediated Damage: Cochlear and Cortical Responses after an Increase in Antioxidant Defense. J. Neurosci. 2013, 33, 4011–4023. [Google Scholar] [CrossRef] [Green Version]
- Fetoni, A.; Rolesi, R.; Paciello, F.; Eramo, S.; Grassi, C.; Troiani, D.; Paludetti, G. Styrene enhances the noise induced oxidative stress in the cochlea and affects differently mechanosensory and supporting cells. Free Radic. Biol. Med. 2016, 101, 211–225. [Google Scholar] [CrossRef]
- Paciello, F.; Di Pino, A.; Rolesi, R.; Troiani, D.; Paludetti, G.; Grassi, C.; Fetoni, A.R. Anti-oxidant and anti-inflammatory effects of caffeic acid: In vivo evidences in a model of noise-induced hearing loss. Food Chem. Toxicol. 2020, 143, 111555. [Google Scholar] [CrossRef]
- Fetoni, A.R.; Mancuso, C.; Eramo, S.L.M.; Ralli, M.; Piacentini, R.; Barone, E.; Paludetti, G.; Troiani, D. In vivo protective effect of ferulic acid against noise-induced hearing loss in the guinea-pig. Neuroscience 2010, 169, 1575–1588. [Google Scholar] [CrossRef]
- Fetoni, A.R.; Paciello, F.; Rolesi, R.; Eramo, S.L.M.; Mancuso, C.; Troiani, D.; Paludetti, G. Rosmarinic acid up-regulates the noise-activated Nrf2/HO-1 pathway and protects against noise-induced injury in rat cochlea. Free Radic. Biol. Med. 2015, 85, 269–281. [Google Scholar] [CrossRef]
- Paciello, F.; Fetoni, A.R.; Mezzogori, D.; Rolesi, R.; Di Pino, A.; Paludetti, G.; Grassi, C.; Troiani, D. The Dual Role of Curcumin and Ferulic Acid in Counteracting Chemoresistance and Cisplatin-Induced Ototoxicity. Sci. Rep. 2020, 10, 1063. [Google Scholar] [CrossRef] [Green Version]
- Paciello, F.; Fetoni, A.R.; Rolesi, R.; Wright, M.B.; Grassi, C.; Troiani, D.; Paludetti, G. Pioglitazone Represents an Effective Therapeutic Target in Preventing Oxidative/Inflammatory Cochlear Damage Induced by Noise Exposure. Front. Pharmacol. 2018, 9, 1103. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Spiegelman, B.M. PPAR-gamma: Adipogenic regulator and thiazolidinedione receptor. Diabetes 1998, 47, 507–514. [Google Scholar] [CrossRef] [PubMed]
- Kersten, S.; Desvergne, B.; Wahli, W. Roles of PPARs in health and disease. Nat. Cell Biol. 2000, 405, 421–424. [Google Scholar] [CrossRef] [PubMed]
- Kumar, B.P.; Kumar, A.P.; Jose, J.A.; Prabitha, P.; Yuvaraj, S.; Chipurupalli, S.; Jeyarani, V.; Manisha, C.; Banerjee, S.; Jeyabalan, J.B.; et al. Minutes of PPAR-γ agonism and neuroprotection. Neurochem. Int. 2020, 140, 104814. [Google Scholar] [CrossRef] [PubMed]
- Cock, T.-A.; Houten, S.M.; Auwerx, J. Peroxisome Proliferator-Activated Receptor-γ: Too Much of a Good Thing Causes Harm. EMBO Rep. 2004, 5, 142–147. [Google Scholar] [CrossRef] [Green Version]
- Mirza, A.Z.; AlThagafi, I.I.; Shamshad, H. Role of PPAR receptor in different diseases and their ligands: Physiological importance and clinical implications. Eur. J. Med. Chem. 2019, 166, 502–513. [Google Scholar] [CrossRef] [PubMed]
- Tontonoz, P.; Spiegelman, B.M. Fat and Beyond: The Diverse Biology of PPARgamma. Annu. Rev. Biochem. 2008, 77, 289–312. [Google Scholar] [CrossRef] [PubMed]
- Collino, M.; Aragno, M.; Mastrocola, R.; Gallicchio, M.; Rosa, A.C.; Dianzani, C.; Danni, O.; Thiemermann, C.; Fantozzi, R. Modulation of the Oxidative Stress and Inflammatory Response by PPAR-Gamma Agonists in the Hippocampus of Rats Exposed to Cerebral Ischemia/Reperfusion. Eur. J. Pharmacol. 2006, 530, 70–80. [Google Scholar] [CrossRef]
- Kim, T.; Yang, Q. Peroxisome-Proliferator-Activated Receptors Regulate Redox Signaling in the Cardiovascular System. World J. Cardiol. 2013, 5, 164–174. [Google Scholar] [CrossRef]
- Galbraith, L.C.A.; Mui, E.; Nixon, C.; Hedley, A.; Strachan, D.; MacKay, G.; Sumpton, D.; Sansom, O.J.; Leung, H.Y.; Ahmad, I. PPAR-gamma induced AKT3 expression increases levels of mitochondrial biogenesis driving prostate cancer. Oncogene 2021, 40, 2355–2366. [Google Scholar] [CrossRef]
- Mandrekar-Colucci, S.; Sauerbeck, A.; Popovich, P.G.; McTigue, D.M. PPAR Agonists as Therapeutics for CNS Trauma and Neurological Diseases. ASN Neuro 2013, 5, AN20130030. [Google Scholar] [CrossRef] [Green Version]
- Yu, J.H.; Kim, K.H.; Kim, H. SOCS 3 and PPAR-Gamma Ligands Inhibit the Expression of IL-6 and TGF-Beta1 by Regulating JAK2/STAT3 Signaling in Pancreas. Int. J. Biochem. Cell Biol. 2008, 40, 677–688. [Google Scholar] [CrossRef] [PubMed]
- Soliman, E.; Behairy, S.F.; El-Maraghy, N.N.; Elshazly, S.M. PPAR-γ agonist, pioglitazone, reduced oxidative and endoplasmic reticulum stress associated with L-NAME-induced hypertension in rats. Life Sci. 2019, 239, 117047. [Google Scholar] [CrossRef]
- Park, C.; Ji, H.-M.; Kim, S.-J.; Kil, S.-H.; Lee, J.N.; Kwak, S.; Choe, S.-K.; Park, R. Fenofibrate exerts protective effects against gentamicin-induced toxicity in cochlear hair cells by activating antioxidant enzymes. Int. J. Mol. Med. 2017, 39, 960–968. [Google Scholar] [CrossRef] [Green Version]
- Sekulic-Jablanovic, M.; Petkovic, V.; Wright, M.B.; Kucharava, K.; Huerzeler, N.; Levano, S.; Brand, Y.; Leitmeyer, K.; Glutz, A.; Bausch, A.; et al. Effects of peroxisome proliferator activated receptors (PPAR)-γ and -α agonists on cochlear protection from oxidative stress. PLoS ONE 2017, 12, e0188596. [Google Scholar] [CrossRef]
- Hou, Y.; Moreau, F.; Chadee, K. PPARγ Is an E3 Ligase That Induces the Degradation of NFκB/P65. Nat. Commun. 2012, 3, 1300. [Google Scholar] [CrossRef] [Green Version]
- Fetoni, A.; Eramo, S.; Rolesi, R.; Troiani, D.; Paludetti, G. Antioxidant treatment with coenzyme Q-ter in prevention of gentamycin ototoxicity in an animal model. Acta Otorhinolaryngol. Ital. 2012, 32, 103–110. [Google Scholar] [PubMed]
- Guan, Y. Peroxisome Proliferator-Activated Receptor Family and Its Relationship to Renal Complications of the Metabolic Syndrome. J. Am. Soc. Nephrol. 2004, 15, 2801–2815. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Daynes, R.A.; Jones, D.C. Emerging roles of PPARS in inflammation and immunity. Nat. Rev. Immunol. 2002, 2, 748–759. [Google Scholar] [CrossRef]
- Kaiser, C.; Knight, A.; Nordström, D.; Pettersson, T.; Fransson, J.; Florin-Robertsson, E.; Pilström, B. Injection-Site Reactions upon Kineret (Anakinra) Administration: Experiences and Explanations. Rheumatol. Int. 2012, 32, 295–299. [Google Scholar] [CrossRef] [Green Version]
- Jesus, A.A.; Goldbach-Mansky, R. IL-1 Blockade in Autoinflammatory Syndromes. Annu. Rev. Med. 2014, 65, 223–244. [Google Scholar] [CrossRef] [Green Version]
- Maulucci, G.; Troiani, D.; Eramo, S.L.M.; Paciello, F.; Podda, M.V.; Paludetti, G.; Papi, M.; Maiorana, A.; Palmieri, V.; De Spirito, M.; et al. Time evolution of noise induced oxidation in outer hair cells: Role of NAD(P)H and plasma membrane fluidity. Biochim. Biophys. Acta (BBA) Gen. Subj. 2014, 1840, 2192–2202. [Google Scholar] [CrossRef] [PubMed]
- Ohlemiller, K.K.; Wright, J.S.; Dugan, L.L. Early Elevation of Cochlear Reactive Oxygen Species following Noise Exposure. Audiol. Neurotol. 1999, 4, 229–236. [Google Scholar] [CrossRef]
- Yamane, H.; Nakai, Y.; Takayama, M.; Iguchi, H.; Nakagawa, T.; Kojima, A. Appearance of free radicals in the guinea pig inner ear after noise-induced acoustic trauma. Eur. Arch. Oto-Rhino-Laryngol. 1995, 252, 504–508. [Google Scholar] [CrossRef] [PubMed]
- Fetoni, A.R.; Paciello, F.; Rolesi, R.; Paludetti, G.; Troiani, D. Targeting dysregulation of redox homeostasis in noise-induced hearing loss: Oxidative stress and ROS signaling. Free Radic. Biol. Med. 2019, 135, 46–59. [Google Scholar] [CrossRef] [PubMed]
- Blanquicett, C.; Kang, B.-Y.; Ritzenthaler, J.D.; Jones, D.P.; Hart, C.M. Oxidative Stress Modulates PPAR Gamma in Vascular Endothelial Cells. Free Radic. Biol. Med. 2010, 48, 1618–1625. [Google Scholar] [CrossRef] [Green Version]
- Poynter, M.E.; Daynes, R.A. Peroxisome Proliferator-Activated Receptor Alpha Activation Modulates Cellular Redox Status, Represses Nuclear Factor-KappaB Signaling, and Reduces Inflammatory Cytokine Production in Aging. J. Biol. Chem. 1998, 273, 32833–32841. [Google Scholar] [CrossRef] [Green Version]
- Gratton, M.A.; Eleftheriadou, A.; Garcia, J.; Verduzco, E.; Martin, G.K.; Lonsbury-Martin, B.L.; Vázquez, A.E. Noise-induced changes in gene expression in the cochleae of mice differing in their susceptibility to noise damage. Hear. Res. 2011, 277, 211–226. [Google Scholar] [CrossRef] [Green Version]
- Nakamoto, T.; Mikuriya, T.; Sugahara, K.; Hirose, Y.; Hashimoto, T.; Shimogori, H.; Takii, R.; Nakai, A.; Yamashita, H. Geranylgeranylacetone suppresses noise-induced expression of proinflammatory cytokines in the cochlea. Auris Nasus Larynx 2012, 39, 270–274. [Google Scholar] [CrossRef] [PubMed]
- Fujioka, M.; Okano, H.; Ogawa, K. Inflammatory and immune responses in the cochlea: Potential therapeutic targets for sensorineural hearing loss. Front. Pharmacol. 2014, 5, 287. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kurabi, A.; Keithley, E.M.; Housley, G.D.; Ryan, A.F.; Wong, A.C.-Y. Cellular mechanisms of noise-induced hearing loss. Hear. Res. 2017, 349, 129–137. [Google Scholar] [CrossRef]
- Haase, G.M.; Prasad, K.N. Oxidative Damage and Inflammation Biomarkers: Strategy in Hearing Disorders. Otol. Neurotol. 2016, 37, e303–e308. [Google Scholar] [CrossRef]
- Kalinec, G.M.; Lomberk, G.; Urrutia, R.A.; Kalinec, F. Resolution of Cochlear Inflammation: Novel Target for Preventing or Ameliorating Drug-, Noise- and Age-related Hearing Loss. Front. Cell Neurosci. 2017, 11, 192. [Google Scholar] [CrossRef] [Green Version]
- Wang, J.; Puel, J.-L. Presbycusis: An Update on Cochlear Mechanisms and Therapies. J. Clin. Med. 2020, 9, 218. [Google Scholar] [CrossRef] [Green Version]
- Varela-Nieto, I.; Murillo-Cuesta, S.; Calvino, M.; Cediel, R.; Lassaletta, L. Drug development for noise-induced hearing loss. Expert Opin. Drug Discov. 2020, 15, 1457–1471. [Google Scholar] [CrossRef] [PubMed]
- Devchand, P.R.; Keller, H.; Peters, J.M.; Vazquez, M.; Gonzalez, F.J.; Wahli, W. The PPARalpha-Leukotriene B4 Pathway to Inflammation Control. Nature 1996, 384, 39–43. [Google Scholar] [CrossRef] [PubMed]
- Chinetti, G.; Lestavel, S.; Bocher, V.; Remaley, A.T.; Neve, B.; Torra, I.P.; Teissier, E.; Minnich, A.; Jaye, M.; Duverger, N.; et al. PPAR-Alpha and PPAR-Gamma Activators Induce Cholesterol Removal from Human Macrophage Foam Cells through Stimulation of the ABCA1 Pathway. Nat. Med. 2001, 7, 53–58. [Google Scholar] [CrossRef]
- Genolet, R.; Wahli, W.; Michalik, L. PPARs as drug targets to modulate inflammatory responses? Curr. Drug Targets-Inflamm. Allergy 2004, 3, 361–375. [Google Scholar] [CrossRef] [PubMed]
- Korbecki, J.; Bobiński, R.; Dutka, M. Self-regulation of the inflammatory response by peroxisome proliferator-activated receptors. Inflamm. Res. 2019, 68, 443–458. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bernardo, A.; Plumitallo, C.; De Nuccio, C.; Visentin, S.; Minghetti, L. Curcumin promotes oligodendrocyte differentiation and their protection against TNF-α through the activation of the nuclear receptor PPAR-γ. Sci. Rep. 2021, 11. [Google Scholar] [CrossRef]
- Bergamini, C.; Moruzzi, N.; Sblendido, A.; Lenaz, G.; Fato, R. A Water Soluble CoQ10 Formulation Improves Intracellular Distribution and Promotes Mitochondrial Respiration in Cultured Cells. PLoS ONE 2012, 7, e33712. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fetoni, A.R.; Piacentini, R.; Fiorita, A.; Paludetti, G.; Troiani, D. Water-soluble Coenzyme Q10 formulation (Q-ter) promotes outer hair cell survival in a guinea pig model of noise induced hearing loss (NIHL). Brain Res. 2009, 1257, 108–116. [Google Scholar] [CrossRef]
- Cavalli, G.; Dinarello, C.A. Anakinra Therapy for Non-cancer Inflammatory Diseases. Front. Pharmacol. 2018, 9, 1157. [Google Scholar] [CrossRef] [Green Version]
- Beg, A.A.; Finco, T.S.; Nantermet, P.V.; Baldwin, A.S. Tumor Necrosis Factor and Interleukin-1 Lead to Phosphorylation and Loss of I Kappa B Alpha: A Mechanism for NF-Kappa B Activation. Mol. Cell Biol. 1993, 13, 3301–3310. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hayden, M.S.; Ghosh, S. Signaling to NF-KappaB. Genes Dev. 2004, 18, 2195–2224. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gonçalves, N.P.; Vieira, P.; Saraiva, M.J. Interleukin-1 signaling pathway as a therapeutic target in transthyretin amyloidosis. Amyloid 2014, 21, 175–184. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhuang, Z.; Ju, H.-Q.; Aguilar, M.; Gocho, T.; Li, H.; Iida, T.; Lee, H.; Fan, X.; Zhou, H.; Ling, J.; et al. IL1 Receptor Antagonist Inhibits Pancreatic Cancer Growth by Abrogating NF-ΚB Activation. Clin. Cancer Res. 2016, 22, 1432–1444. [Google Scholar] [CrossRef] [Green Version]
- Herrington, F.D.; Carmody, R.J.; Goodyear, C.S. Modulation of NF-ΚB Signaling as a Therapeutic Target in Autoimmunity. J. Biomol. Screen 2016, 21, 223–242. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gloire, G.; Legrand-Poels, S.; Piette, J. NF-KappaB Activation by Reactive Oxygen Species: Fifteen Years Later. Biochem. Pharmacol. 2006, 72, 1493–1505. [Google Scholar] [CrossRef]
- Blaser, H.; Dostert, C.; Mak, T.W.; Brenner, D. TNF and ROS Crosstalk in Inflammation. Trends Cell Biol. 2016, 26, 249–261. [Google Scholar] [CrossRef]
- Nunn, A.V.W.; Bell, J.; Barter, P. The integration of lipid-sensing and anti-inflammatory effects: How the PPARs play a role in metabolic balance. Nucl. Recept. 2007, 5, 1. [Google Scholar] [CrossRef] [Green Version]
- Pershadsingh, H.A. Alpha-Lipoic Acid: Physiologic Mechanisms and Indications for the Treatment of Metabolic Syndrome. Expert Opin. Investig. Drugs 2007, 16, 291–302. [Google Scholar] [CrossRef]
- Wang, R.; Li, J.J.; Diao, S.; Kwak, Y.-D.; Liu, L.; Zhi, L.; Büeler, H.; Bhat, N.R.; Williams, R.W.; Park, E.A.; et al. Metabolic Stress Modulates Alzheimer’s β-Secretase Gene Transcription via SIRT1-PPARγ-PGC-1 in Neurons. Cell Metab. 2013, 17, 685–694. [Google Scholar] [CrossRef] [Green Version]
- Cannizzaro, L.; Rossoni, G.; Savi, F.; Altomare, A.; Marinello, C.; Saethang, T.; Carini, M.; Payne, D.M.; Pisitkun, T.; Aldini, G.; et al. Regulatory landscape of AGE-RAGE-oxidative stress axis and its modulation by PPARγ activation in high fructose diet-induced metabolic syndrome. Nutr. Metab. 2017, 14, 5. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Feng, X.; Yu, W.; Li, X.; Zhou, F.; Zhang, W.; Shen, Q.; Li, J.; Zhang, C.; Shen, P. Apigenin, a modulator of PPARγ, attenuates HFD-induced NAFLD by regulating hepatocyte lipid metabolism and oxidative stress via Nrf2 activation. Biochem. Pharmacol. 2017, 136, 136–149. [Google Scholar] [CrossRef] [PubMed]
- Polvani, S.; Tarocchi, M.; Galli, A. PPARγ and Oxidative Stress: Con(β) Catenating NRF2 and FOXO. PPAR Res. 2012, 2012, 641087. [Google Scholar] [CrossRef] [Green Version]
- Reddy, R.C.; Standiford, T.J. Nrf2 and PPAR{gamma}: PPARtnering against Oxidant-Induced Lung Injury. Am. J. Respir. Crit. Care Med. 2010, 182, 134–135. [Google Scholar] [CrossRef]
- Huang, J.; Tabbi-Anneni, I.; Gunda, V.; Wang, L. Transcription factor Nrf2 regulates SHP and lipogenic gene expression in hepatic lipid metabolism. Am. J. Physiol. Liver Physiol. 2010, 299, G1211–G1221. [Google Scholar] [CrossRef] [PubMed] [Green Version]
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Paciello, F.; Pisani, A.; Rolesi, R.; Escarrat, V.; Galli, J.; Paludetti, G.; Grassi, C.; Troiani, D.; Fetoni, A.R. Noise-Induced Cochlear Damage Involves PPAR Down-Regulation through the Interplay between Oxidative Stress and Inflammation. Antioxidants 2021, 10, 1188. https://doi.org/10.3390/antiox10081188
Paciello F, Pisani A, Rolesi R, Escarrat V, Galli J, Paludetti G, Grassi C, Troiani D, Fetoni AR. Noise-Induced Cochlear Damage Involves PPAR Down-Regulation through the Interplay between Oxidative Stress and Inflammation. Antioxidants. 2021; 10(8):1188. https://doi.org/10.3390/antiox10081188
Chicago/Turabian StylePaciello, Fabiola, Anna Pisani, Rolando Rolesi, Vincent Escarrat, Jacopo Galli, Gaetano Paludetti, Claudio Grassi, Diana Troiani, and Anna Rita Fetoni. 2021. "Noise-Induced Cochlear Damage Involves PPAR Down-Regulation through the Interplay between Oxidative Stress and Inflammation" Antioxidants 10, no. 8: 1188. https://doi.org/10.3390/antiox10081188
APA StylePaciello, F., Pisani, A., Rolesi, R., Escarrat, V., Galli, J., Paludetti, G., Grassi, C., Troiani, D., & Fetoni, A. R. (2021). Noise-Induced Cochlear Damage Involves PPAR Down-Regulation through the Interplay between Oxidative Stress and Inflammation. Antioxidants, 10(8), 1188. https://doi.org/10.3390/antiox10081188