Antioxidant Mitoquinone Alleviates Chronic Pancreatitis via Anti-Fibrotic and Antioxidant Effects

References

• Beyer G, Habtezion A, Werner J, Lerch MM, Mayerle J. Chronic pancreatitis. Lancet. 2020;396(10249):499–512.
   PubMed Web of Science ®Google Scholar
• Kirkegård J, Mortensen FV, Cronin-Fenton D. Chronic Pancreatitis and Pancreatic Cancer Risk: a Systematic Review and Meta-analysis. Am J Gastroenterol. 2017;112(9):1366–1372.
   PubMed Web of Science ®Google Scholar
• Singh VK, Yadav D, Garg PK. Diagnosis and Management of Chronic Pancreatitis: a Review. JAMA. 2019;322(24):2422–2434.
   PubMed Web of Science ®Google Scholar
• Ferdek PE, Jakubowska MA. Biology of pancreatic stellate cells-more than just pancreatic cancer. Eur j Physiol. 2017;469(9):1039–1050.
   PubMed Web of Science ®Google Scholar
• Apte MV, Haber PS, Applegate TL, et al. Periacinar stellate shaped cells in rat pancreas: identification, isolation, and culture. Gut. 1998;43(1):128–133.
   PubMed Web of Science ®Google Scholar
• Xue R, Jia K, Wang J, et al. A Rising Star in Pancreatic Diseases: pancreatic Stellate Cells. Front Physiol. 2018;9:754.
   PubMed Web of Science ®Google Scholar
• Bynigeri RR, Jakkampudi A, Jangala R, et al. Pancreatic stellate cell: pandora’s box for pancreatic disease biology. World j Gastroenterol. 2017;23(3):382–405.
   PubMed Web of Science ®Google Scholar
• Ramakrishnan P, Loh WM, Gopinath SCB, et al. Selective phytochemicals targeting pancreatic stellate cells as new anti-fibrotic agents for chronic pancreatitis and pancreatic cancer. Acta Pharm Sin B. 2020;10(3):399–413.
   PubMed Web of Science ®Google Scholar
• Zhao Q, Manohar M, Wei Y, Pandol SJ, Habtezion A. STING signalling protects against chronic pancreatitis by modulating Th17 response. Gut. 2019;68(10):1827–1837.
   PubMed Web of Science ®Google Scholar
• Li L, Wang G, Hu JS, et al. RB1CC1-enhanced autophagy facilitates PSCs activation and pancreatic fibrogenesis in chronic pancreatitis. Cell Death Dis. 2018;9(10):952.
   PubMed Web of Science ®Google Scholar
• Kim JJ, Lee E, Ryu GR, Ko SH, Ahn YB, Song KH. Hypoxia Increases β-Cell Death by Activating Pancreatic Stellate Cells within the Islet. Diabetes Metab J. 2020;44(6):919–927.
   PubMed Web of Science ®Google Scholar
• Ren Y, Zhang J, Wang M, et al. Identification of irisin as a therapeutic agent that inhibits oxidative stress and fibrosis in a murine model of chronic pancreatitis. Biomed Pharmacother. 2020;126:110101.
   PubMed Web of Science ®Google Scholar
• Tandon RK, Garg PK. Oxidative stress in chronic pancreatitis: pathophysiological relevance and management. Antioxid Redox Signal. 2011;15(10):2757–2766.
   PubMed Web of Science ®Google Scholar
• Daher B, Parks SK, Durivault J, et al. Genetic Ablation of the Cystine Transporter xCT in PDAC Cells Inhibits mTORC1, Growth, Survival, and Tumor Formation via Nutrient and Oxidative Stresses. Cancer Res. 2019;79(15):3877–3890.
   PubMed Web of Science ®Google Scholar
• Kim JW, Park SY, You YH, et al. Suppression of ROS Production by Exendin-4 in PSC Attenuates the High Glucose-Induced Islet Fibrosis. PLoS One. 2016;11(12):e0163187.
   PubMed Web of Science ®Google Scholar
• Tasci I, Deveci S, Isik AT, et al. Allopurinol in rat chronic pancreatitis: effects on pancreatic stellate cell activation. Pancreas. 2007;35(4):366–371.
   PubMed Web of Science ®Google Scholar
• Xue R, Wang J, Yang L, et al. Coenzyme Q10 Ameliorates Pancreatic Fibrosis via the ROS-Triggered mTOR Signaling Pathway. Oxid Med Cell Longev. 2019;2019:8039694.
   PubMed Web of Science ®Google Scholar
• Wang Y, Branicky R, Noë A, Hekimi S. Superoxide dismutases: dual roles in controlling ROS damage and regulating ROS signaling. J Cell Biol. 2018;217(6):1915–1928.
   PubMed Web of Science ®Google Scholar
• Bhatti JS, Bhatti GK, Reddy PH. Mitochondrial dysfunction and oxidative stress in metabolic disorders - A step towards mitochondria based therapeutic strategies. Biochim Biophys Acta Mol Basis Dis. 2017;1863(5):1066–1077.
   PubMed Web of Science ®Google Scholar
• Poprac P, Jomova K, Simunkova M, Kollar V, Rhodes CJ, Valko M. Targeting Free Radicals in Oxidative Stress-Related Human Diseases. Trends Pharmacol Sci. 2017;38(7):592–607.
   PubMed Web of Science ®Google Scholar
• Smith RA, Murphy MP. Animal and human studies with the mitochondria-targeted antioxidant MitoQ. Ann N Y Acad Sci. 2010;1201:96–103.
   PubMed Web of Science ®Google Scholar
• Mukhopadhyay P, Horváth B, Zsengellėr Z, et al. Mitochondrial reactive oxygen species generation triggers inflammatory response and tissue injury associated with hepatic ischemia-reperfusion: therapeutic potential of mitochondrially targeted antioxidants. Free Radic Biol Med. 2012;53(5):1123–1138.
   PubMed Web of Science ®Google Scholar
• Gane EJ, Weilert F, Orr DW, et al. The mitochondria-targeted anti-oxidant mitoquinone decreases liver damage in a Phase II study of hepatitis C patients. Liver Int. 2010;30(7):1019–1026.
   PubMed Web of Science ®Google Scholar
• Vilaseca M, García-Calderó H, Lafoz E, et al. Mitochondria-targeted antioxidant mitoquinone deactivates human and rat hepatic stellate cells and reduces portal hypertension in cirrhotic rats. Liver Int. 2017;37(7):1002–1012.
   PubMed Web of Science ®Google Scholar
• Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010;8(6):e1000412.
   PubMed Web of Science ®Google Scholar
• Klauss S, Schorn S, Teller S, et al. Genetically induced vs. classical animal models of chronic pancreatitis: a critical comparison. FASEB j. 2018;1:fj201800241RR.
   Google Scholar
• Lerch MM, Gorelick FS. Models of acute and chronic pancreatitis. Gastroenterology. 2013;144(6):1180–1193.
   PubMed Web of Science ®Google Scholar
• Li Z, Zhang X, Jin T, Hao J. Nicotine promotes activation of human pancreatic stellate cells through inducing autophagy via α7nAChR-mediated JAK2/STAT3 signaling pathway. Life Sci. 2020;243:117301.
   PubMed Web of Science ®Google Scholar
• Fridovich I. Superoxide anion radical (O2-.), superoxide dismutases, and related matters. J Biol Chem. 1997;272(30):18515–18517.
   PubMed Web of Science ®Google Scholar
• Martinez-Useros J, Li W, Cabeza-Morales M, Garcia-Foncillas J. Oxidative Stress: a New Target for Pancreatic Cancer Prognosis and Treatment. J Clin Med. 2017;6:3.
   PubMed Web of Science ®Google Scholar
• Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev. 2007;87(1):245–313.
   PubMed Web of Science ®Google Scholar
• Sherman MH. Stellate Cells in Tissue Repair, Inflammation, and Cancer. Annu Rev Cell Dev Biol. 2018;34:333–355.
   PubMed Web of Science ®Google Scholar
• An W, Zhu JW, Jiang F, et al. Fibromodulin is upregulated by oxidative stress through the MAPK/AP-1 pathway to promote pancreatic stellate cell activation. Pancreatology. 2020;20(2):278–287.
   PubMed Web of Science ®Google Scholar
• Aviello G, Knaus UG. NADPH oxidases and ROS signaling in the gastrointestinal tract. Mucosal Immunol. 2018;11(4):1011–1023.
   PubMed Web of Science ®Google Scholar
• Swentek L, Chung D, Ichii H. Antioxidant Therapy in Pancreatitis. Antioxidants. 2021;10:5.
   Web of Science ®Google Scholar
• Gu H, Werner J, Bergmann F, Whitcomb DC, Büchler MW, Fortunato F. Necro-inflammatory response of pancreatic acinar cells in the pathogenesis of acute alcoholic pancreatitis. Cell Death Dis. 2013;4(10):e816.
   PubMed Web of Science ®Google Scholar
• Sendler M, van den Brandt C, Glaubitz J, et al. NLRP3 Inflammasome Regulates Development of Systemic Inflammatory Response and Compensatory Anti-Inflammatory Response Syndromes in Mice With Acute Pancreatitis. Gastroenterology. 2020;158(1):253–69.e14.
   PubMed Web of Science ®Google Scholar
• Xue J, Sharma V, Hsieh MH, et al. Alternatively activated macrophages promote pancreatic fibrosis in chronic pancreatitis. Nat Commun. 2015;6:7158.
   PubMed Web of Science ®Google Scholar
• Singh N, Ahuja V, Sachdev V, et al. Antioxidants for Pancreatic Functions in Chronic Pancreatitis: a Double-blind Randomized Placebo-controlled Pilot Study. J Clin Gastroenterol. 2020;54(3):284–293.
   PubMed Web of Science ®Google Scholar
• Bhardwaj P, Garg PK, Maulik SK, Saraya A, Tandon RK, Acharya SK. A randomized controlled trial of antioxidant supplementation for pain relief in patients with chronic pancreatitis. Gastroenterology. 2009;136(1):149–59.e2.
   PubMed Web of Science ®Google Scholar
• Siriwardena AK, Mason JM, Sheen AJ, Makin AJ, Shah NS. Antioxidant therapy does not reduce pain in patients with chronic pancreatitis: the ANTICIPATE study. Gastroenterology. 2012;143(3):655–63.e1.
   PubMed Web of Science ®Google Scholar
• Rustagi T, Njei B. Antioxidant therapy for pain reduction in patients with chronic pancreatitis: a systematic review and meta-analysis. Pancreas. 2015;44(5):812–818.
   PubMed Web of Science ®Google Scholar
• Masamune A, Kikuta K, Satoh M, Satoh A, Shimosegawa T. Alcohol activates activator protein-1 and mitogen-activated protein kinases in rat pancreatic stellate cells. J Pharmacol Exp Ther. 2002;302(1):36–42.
   PubMed Web of Science ®Google Scholar
• Kikuta K, Masamune A, Satoh M, Suzuki N, Satoh K, Shimosegawa T. Hydrogen peroxide activates activator protein-1 and mitogen-activated protein kinases in pancreatic stellate cells. Mol Cell Biochem. 2006;291(1–2):11–20.
   PubMed Web of Science ®Google Scholar
• Huang W, Cash N, Wen L, et al. Effects of the mitochondria-targeted antioxidant mitoquinone in murine acute pancreatitis. Mediators Inflamm. 2015;2015:901780.
   PubMed Web of Science ®Google Scholar
• Rossman MJ, Santos-Parker JR, Steward CAC, et al. Chronic Supplementation With a Mitochondrial Antioxidant (MitoQ) Improves Vascular Function in Healthy Older Adults. Hypertension. 2018;71(6):1056–1063.
   PubMed Web of Science ®Google Scholar
• Williamson J, Hughes CM, Cobley JN, Davison GW. The mitochondria-targeted antioxidant MitoQ, attenuates exercise-induced mitochondrial DNA damage. Redox Biol. 2020;36:101673.
   PubMed Web of Science ®Google Scholar
• Van Remmen H, Ikeno Y, Hamilton M, et al. Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging. Physiol Genomics. 2003;16(1):29–37.
   PubMed Web of Science ®Google Scholar
• Elchuri S, Oberley TD, Qi W, et al. CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life. Oncogene. 2005;24(3):367–380.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Unnikrishnan A, Deepa SS, et al. A new role for oxidative stress in aging: the accelerated aging phenotype in Sod1(-/)(-) mice is correlated to increased cellular senescence. Redox Biol. 2017;11:30–37.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Ikeno Y, Bokov A, et al. Dietary restriction attenuates the accelerated aging phenotype of Sod1(-/-) mice. Free Radic Biol Med. 2013;60:300–306.
   PubMed Web of Science ®Google Scholar
• Iuchi Y, Roy D, Okada F, et al. Spontaneous skin damage and delayed wound healing in SOD1-deficient mice. Mol Cell Biochem. 2010;341(1–2):181–194.
   PubMed Web of Science ®Google Scholar