{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:37:00Z","timestamp":1785307020562,"version":"3.55.0"},"reference-count":89,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T00:00:00Z","timestamp":1610582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T00:00:00Z","timestamp":1610582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fipronil (FIP) is a phenylpyrazole insecticide that is commonly used in agricultural and veterinary fields for controlling a wide range of insects, but it is a strong environmentally toxic substance. Exposure to FIP has been reported to increase the hepatic fat accumulation through altered lipid metabolism, which ultimately can contribute to nonalcoholic fatty liver disease (NAFLD) development. The\u00a0present\u00a0study\u00a0aimed to examine the function of cerium oxide nanoparticles (CeNPs) in protecting against hepatotoxicity and lipogenesis induced by FIP. Twenty-eight male albino rats were classified into four groups: FIP (5\u00a0mg\/kg\/day per os), CTR, CeNPs (35\u00a0mg\/kg\/day p.o.), and FIP\u2009+\u2009CeNPs (5 (FIP)\u2009+\u200935 (CeNPs) mg\/kg\/day p.o.) for 28 consecutive days. Serum lipid profiles, hepatic antioxidant parameters and pathology, and mRNA expression of adipocytokines were assessed. The results revealed that FIP increased cholesterol, height-density lipoprotein, triacylglyceride, low-density lipoprotein (LDL-c), and very-low-density lipoprotein (VLDL-c) concentrations. It also increased nitric oxide (NO) and malondialdehyde (MDA) hepatic levels and reduced glutathione peroxidase (GPx) and superoxide dismutase (SOD) enzyme activities. Additionally, FIP up-regulated the fatty acid-binding protein (FABP), acetyl Co-A carboxylase (ACC1), and peroxisome proliferator-activated receptor-alpha (PPAR-\u03b1). Immunohistochemically, a strong proliferation of cell nuclear antigen (PCNA), ionized calcium-binding adapter molecule 1 (Iba-1), cyclooxygenase-2 (COX-2) reactions in the endothelial cells of the hepatic sinusoids, and increased expression of caspase3 were observed following FIP intoxication. FIP also caused histological changes in hepatic tissue. The CeNPs counteracted the hepatotoxic effect of FIP exposure. So, this study recorded an ameliorative effect of CeNPs against FIP-induced hepatotoxicity.<\/jats:p>","DOI":"10.1038\/s41598-020-79479-5","type":"journal-article","created":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T11:11:08Z","timestamp":1610622668000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["The potential ameliorative impacts of cerium oxide nanoparticles against fipronil-induced hepatic steatosis"],"prefix":"10.1038","volume":"11","author":[{"given":"Lamiaa","family":"Wasef","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atef M. K.","family":"Nassar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasser S.","family":"El-Sayed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalia","family":"Samak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Noreldin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norhan","family":"Elshony","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamida","family":"Saleh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaser H. A.","family":"Elewa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaimaa M. A.","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah A.","family":"Saati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helal F.","family":"Hetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaber El-Saber","family":"Batiha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakazu","family":"Umezawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazem M.","family":"Shaheen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,14]]},"reference":[{"key":"79479_CR1","doi-asserted-by":"publisher","first-page":"10769","DOI":"10.1038\/s41598-018-29104-3","volume":"8","author":"AA Al-Badran","year":"2018","unstructured":"Al-Badran, A. A., Fujiwara, M., Gatlin, D. M. & Mora, M. A. Lethal and sub-lethal effects of the insecticide fipronil on juvenile brown shrimp Farfantepenaeus aztecus. Sci. Rep. 8, 10769. https:\/\/doi.org\/10.1038\/s41598-018-29104-3 (2018).","journal-title":"Sci. Rep."},{"key":"79479_CR2","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s11356-014-3470-y","volume":"22","author":"N Simon-Delso","year":"2015","unstructured":"Simon-Delso, N. et al. Systemic insecticides (neonicotinoids and fipronil): trends, uses, mode of action and metabolites. Environ. Sci. Pollut. Res. 22, 5\u201334 (2015).","journal-title":"Environ. Sci. Pollut. Res."},{"key":"79479_CR3","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.etap.2015.06.013","volume":"40","author":"MA Tavares","year":"2015","unstructured":"Tavares, M. A. et al. Comparative effects of fipronil and its metabolites sulfone and desulfinyl on the isolated rat liver mitochondria. Environ. Toxicol. Pharmacol. 40, 206\u2013214. https:\/\/doi.org\/10.1016\/j.etap.2015.06.013 (2015).","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"79479_CR4","volume-title":"SoK: Research Perspectives and Challenges for Bitcoin and Cryptocurrencies","author":"J Bonneau","year":"2015","unstructured":"Bonneau, J. et al. SoK: Research Perspectives and Challenges for Bitcoin and Cryptocurrencies (Springer, New York, 2015)."},{"key":"79479_CR5","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.cbi.2006.09.013","volume":"164","author":"PC Das","year":"2006","unstructured":"Das, P. C., Cao, Y., Cherrington, N., Hodgson, E. & Rose, R. L. Fipronil induces CYP isoforms and cytotoxicity in human hepatocytes. Chem. Biol. Interact. 164, 200\u2013214 (2006).","journal-title":"Chem. Biol. Interact."},{"key":"79479_CR6","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.pestbp.2015.03.010","volume":"124","author":"S Khan","year":"2015","unstructured":"Khan, S., Jan, M., Kumar, D. & Telang, A. Firpronil induced spermotoxicity is associated with oxidative stress, DNA damage and apoptosis in male rats. Pestic. Biochem. Physiol. 124, 8\u201314 (2015).","journal-title":"Pestic. Biochem. Physiol."},{"key":"79479_CR7","doi-asserted-by":"publisher","first-page":"E23","DOI":"10.1073\/pnas.1522687112","volume":"113","author":"B-E Ahn","year":"2016","unstructured":"Ahn, B.-E. & Baker, T. A. Oxidization without substrate unfolding triggers proteolysis of the peroxide-sensor, PerR. Proc. Natl. Acad. Sci. 113, E23\u2013E31 (2016).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"79479_CR8","doi-asserted-by":"crossref","unstructured":"Poljsak, B., \u0160uput, D. & Milisav, I. Achieving the balance between ROS and antioxidants: when to use the synthetic antioxidants. Oxid. Med. Cell. Long. 2013 (2013).","DOI":"10.1155\/2013\/956792"},{"key":"79479_CR9","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1136\/jcp.54.3.176","volume":"54","author":"I Young","year":"2001","unstructured":"Young, I. & Woodside, J. Antioxidants in health and disease. J. Clin. Pathol. 54, 176\u2013186 (2001).","journal-title":"J. Clin. Pathol."},{"key":"79479_CR10","doi-asserted-by":"publisher","first-page":"242","DOI":"10.3389\/fphys.2013.00242","volume":"4","author":"S Pizzimenti","year":"2013","unstructured":"Pizzimenti, S. et al. Interaction of aldehydes derived from lipid peroxidation and membrane proteins. Front. Physiol. 4, 242 (2013).","journal-title":"Front. Physiol."},{"key":"79479_CR11","doi-asserted-by":"publisher","first-page":"8s","DOI":"10.1111\/j.1530-0277.2001.tb02368.x","volume":"25","author":"AM Diehl","year":"2001","unstructured":"Diehl, A. M. Nonalcoholic fatty liver disease: implications for alcoholic liver disease pathogenesis. Alcohol. Clin. Exp. Res. 25, 8s\u201314s (2001).","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"79479_CR12","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1089\/ars.2012.5149","volume":"20","author":"M Mittal","year":"2014","unstructured":"Mittal, M., Siddiqui, M. R., Tran, K., Reddy, S. P. & Malik, A. B. Reactive oxygen species in inflammation and tissue injury. Antioxid. Redox Signal. 20, 1126\u20131167 (2014).","journal-title":"Antioxid. Redox Signal."},{"key":"79479_CR13","doi-asserted-by":"publisher","first-page":"4527","DOI":"10.1042\/bcj20160503c","volume":"473","author":"P Newsholme","year":"2016","unstructured":"Newsholme, P. et al. Molecular mechanisms of ROS production and oxidative stress in diabetes. Biochem. J. 473, 4527\u20134550. https:\/\/doi.org\/10.1042\/bcj20160503c (2016).","journal-title":"Biochem. J."},{"key":"79479_CR14","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.3390\/ijerph120201253","volume":"12","author":"J Dahle","year":"2015","unstructured":"Dahle, J. & Arai, Y. Environmental geochemistry of cerium: applications and toxicology of cerium oxide nanoparticles. Int. J. Environ. Res. Public Health 12, 1253\u20131278 (2015).","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"79479_CR15","doi-asserted-by":"publisher","first-page":"e90","DOI":"10.1038\/am.2013.88","volume":"6","author":"C Xu","year":"2014","unstructured":"Xu, C. & Qu, X. Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Mater. 6, e90 (2014).","journal-title":"NPG Asia Mater."},{"key":"79479_CR16","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1007\/s13346-013-0136-0","volume":"3","author":"JM Dowding","year":"2013","unstructured":"Dowding, J. M., Seal, S. & Self, W. T. Cerium oxide nanoparticles accelerate the decay of peroxynitrite (ONOO\u2212). Drug Deliv. Transl. Res. 3, 375\u2013379 (2013).","journal-title":"Drug Deliv. Transl. Res."},{"key":"79479_CR17","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.bcp.2014.08.015","volume":"92","author":"F Caputo","year":"2014","unstructured":"Caputo, F., De Nicola, M. & Ghibelli, L. Pharmacological potential of bioactive engineered nanomaterials. Biochem. Pharmacol. 92, 112\u2013130. https:\/\/doi.org\/10.1016\/j.bcp.2014.08.015 (2014).","journal-title":"Biochem. Pharmacol."},{"key":"79479_CR18","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1002\/jbm.a.31514","volume":"84","author":"DG Olmedo","year":"2008","unstructured":"Olmedo, D. G., Tasat, D. R., Evelson, P., Guglielmotti, M. B. & Cabrini, R. L. Biological response of tissues with macrophagic activity to titanium dioxide. J. Biomed. Mater. Res. A 84, 1087\u20131093 (2008).","journal-title":"J. Biomed. Mater. Res. A"},{"key":"79479_CR19","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.fct.2015.06.019","volume":"83","author":"M Caballero","year":"2015","unstructured":"Caballero, M. et al. Fipronil induces CYP isoforms in rats. Food Chem. Toxicol. 83, 215\u2013221 (2015).","journal-title":"Food Chem. Toxicol."},{"key":"79479_CR20","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.fct.2018.01.055","volume":"114","author":"MM Abdel-Daim","year":"2018","unstructured":"Abdel-Daim, M. M. & Abdeen, A. Protective effects of rosuvastatin and vitamin E against fipronil-mediated oxidative damage and apoptosis in rat liver and kidney. Food Chem. Toxicol. 114, 69\u201377. https:\/\/doi.org\/10.1016\/j.fct.2018.01.055 (2018).","journal-title":"Food Chem. Toxicol."},{"key":"79479_CR21","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.jtemb.2017.02.013","volume":"41","author":"MR Khaksar","year":"2017","unstructured":"Khaksar, M. R. et al. Protective effects of cerium oxide and yttrium oxide nanoparticles on reduction of oxidative stress induced by sub-acute exposure to diazinon in the rat pancreas. J. Trace Elem. Med Biol. 41, 79\u201390 (2017).","journal-title":"J. Trace Elem. Med Biol."},{"key":"79479_CR22","volume-title":"Determination of Nitrite and Nitrate Content in Water","author":"J Renaudin","year":"2001","unstructured":"Renaudin, J. Determination of Nitrite and Nitrate Content in Water (Springer, New York, 2001)."},{"key":"79479_CR23","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1016\/S0006-291X(72)80218-3","volume":"46","author":"M Nishikimi","year":"1972","unstructured":"Nishikimi, M., Rao, N. A. & Yagi, K. The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochem. Biophys. Res. Commun. 46, 849\u2013854 (1972).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"79479_CR24","first-page":"158","volume":"70","author":"DE Paglia","year":"1967","unstructured":"Paglia, D. E. & Valentine, W. N. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Lab. Clin. Med. 70, 158\u2013169 (1967).","journal-title":"J. Lab. Clin. Med."},{"key":"79479_CR25","doi-asserted-by":"crossref","unstructured":"Bancroft, J. D. & Layton, C. in Bancroft s Theory and practice of histological techniques (ed Christopher Layton and John D. Bancroft S. Kim suvarna) 173\u2013186 (Churchill Livingstone:, 2013).","DOI":"10.1016\/B978-0-7020-4226-3.00010-X"},{"key":"79479_CR26","doi-asserted-by":"crossref","unstructured":"27Layton, C. & Bancroft, J. D. in Bancroft s Theory and practice of histological techniques (ed C. Layton, J. D. B. S. Kim Suvarna) 215\u2013238 (Churchill Livingstone, 2013).","DOI":"10.1016\/B978-0-7020-4226-3.00012-3"},{"key":"79479_CR27","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1177\/0300985813485099","volume":"50","author":"KN Gibson-Corley","year":"2013","unstructured":"Gibson-Corley, K. N., Olivier, A. K. & Meyerholz, D. K. Principles for valid histopathologic scoring in research. Vet. Pathol. 50, 1007\u20131015. https:\/\/doi.org\/10.1177\/0300985813485099 (2013).","journal-title":"Vet. Pathol."},{"key":"79479_CR28","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.acthis.2015.12.001","volume":"118","author":"AE Noreldin","year":"2016","unstructured":"Noreldin, A. E. et al. Spatial distribution of osteoblast activating peptide in the rat stomach. Acta Histochem. 118, 109\u2013117. https:\/\/doi.org\/10.1016\/j.acthis.2015.12.001 (2016).","journal-title":"Acta Histochem."},{"key":"79479_CR29","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/j.acthis.2018.03.001","volume":"120","author":"AE Noreldin","year":"2018","unstructured":"Noreldin, A. E., Elewa, Y. H. A., Kon, Y., Warita, K. & Hosaka, Y. Z. Immunohistochemical localization of osteoblast activating peptide in the mouse kidney. Acta Histochem. 120, 323\u2013328 (2018).","journal-title":"Acta Histochem."},{"key":"79479_CR30","first-page":"4203","volume":"33","author":"AM Sysel","year":"2013","unstructured":"Sysel, A. M., Valli, V. E., Nagle, R. B. & Bauer, J. A. Immunohistochemical quantification of the vitamin B12 transport protein (TCII), cell surface receptor (TCII-R) and Ki-67 in human tumor xenografts. Anticancer Res. 33, 4203\u20134212 (2013).","journal-title":"Anticancer Res."},{"key":"79479_CR31","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1309\/CQWY-E3F6-9KDN-YV36","volume":"113","author":"AN Vis","year":"2000","unstructured":"Vis, A. N., Kranse, R., Nigg, A. L. & van der Kwast, T. H. Quantitative analysis of the decay of immunoreactivity in stored prostate needle biopsy sections. Am. J. Clin. Pathol. 113, 369\u2013373. https:\/\/doi.org\/10.1309\/CQWY-E3F6-9KDN-YV36 (2000).","journal-title":"Am. J. Clin. Pathol."},{"key":"79479_CR32","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.pestbp.2014.10.013","volume":"118","author":"PC Badgujar","year":"2015","unstructured":"Badgujar, P. C., Pawar, N. N., Chandratre, G. A., Telang, A. & Sharma, A. Fipronil induced oxidative stress in kidney and brain of mice: Protective effect of vitamin E and vitamin C. Pestic. Biochem. Physiol. 118, 10\u201318 (2015).","journal-title":"Pestic. Biochem. Physiol."},{"key":"79479_CR33","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.toxlet.2016.04.005","volume":"252","author":"A Romero","year":"2016","unstructured":"Romero, A. et al. Fipronil sulfone induced higher cytotoxicity than fipronil in SH-SY5Y cells: Protection by antioxidants. Toxicol. Lett. 252, 42\u201349 (2016).","journal-title":"Toxicol. Lett."},{"key":"79479_CR34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/02772248.2017.1393818","volume":"99","author":"QC Sun","year":"2017","unstructured":"Sun, Q. C., Clark, J. & Park, Y. Environmental pollutants and type 2 diabetes: A review of human studies. Toxicol. Environ. Chem. 99, 1\u201342. https:\/\/doi.org\/10.1080\/02772248.2017.1393818 (2017).","journal-title":"Toxicol. Environ. Chem."},{"key":"79479_CR35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/cphy.c170012","volume":"8","author":"M Alves-Bezerra","year":"2017","unstructured":"Alves-Bezerra, M. & Cohen, D. E. Triglyceride metabolism in the liver. Compr. Physiol. 8, 1\u20138. https:\/\/doi.org\/10.1002\/cphy.c170012 (2017).","journal-title":"Compr. Physiol."},{"key":"79479_CR36","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/j.jhep.2012.08.018","volume":"58","author":"T-M Leung","year":"2013","unstructured":"Leung, T.-M. & Nieto, N. CYP2E1 and oxidant stress in alcoholic and non-alcoholic fatty liver disease. J. Hepatol. 58, 395\u2013398 (2013).","journal-title":"J. Hepatol."},{"key":"79479_CR37","doi-asserted-by":"publisher","first-page":"1544","DOI":"10.3390\/nu5051544","volume":"5","author":"M Gaggini","year":"2013","unstructured":"Gaggini, M. et al. Non-alcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease. Nutrients 5, 1544\u20131560 (2013).","journal-title":"Nutrients"},{"key":"79479_CR38","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/s12916-017-0806-8","volume":"15","author":"BA Neuschwander-Tetri","year":"2017","unstructured":"Neuschwander-Tetri, B. A. Non-alcoholic fatty liver disease. BMC Med. 15, 45 (2017).","journal-title":"BMC Med."},{"key":"79479_CR39","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1172\/JCI23621","volume":"115","author":"KL Donnelly","year":"2005","unstructured":"Donnelly, K. L. et al. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J. Clin. Investig. 115, 1343\u20131351 (2005).","journal-title":"J. Clin. Investig."},{"key":"79479_CR40","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1016\/j.cmet.2010.04.001","volume":"11","author":"SA Hawley","year":"2010","unstructured":"Hawley, S. A. et al. Use of cells expressing \u03b3 subunit variants to identify diverse mechanisms of AMPK activation. Cell Metab. 11, 554\u2013565 (2010).","journal-title":"Cell Metab."},{"key":"79479_CR41","doi-asserted-by":"publisher","first-page":"43074","DOI":"10.1074\/jbc.M308484200","volume":"278","author":"W Yin","year":"2003","unstructured":"Yin, W., Mu, J. & Birnbaum, M. J. Role of AMP-activated protein kinase in cyclic AMP-dependent lipolysis in 3T3-L1 adipocytes. J. Biol. Chem. 278, 43074\u201343080 (2003).","journal-title":"J. Biol. Chem."},{"key":"79479_CR42","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1042\/BJ20061479","volume":"403","author":"H-J Koh","year":"2007","unstructured":"Koh, H.-J. et al. Adrenaline is a critical mediator of acute exercise-induced AMP-activated protein kinase activation in adipocytes. Biochem. J. 403, 473\u2013481 (2007).","journal-title":"Biochem. J."},{"key":"79479_CR43","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/0955-0674(92)90037-D","volume":"4","author":"BF Trump","year":"1992","unstructured":"Trump, B. F. & Berezesky, I. K. The role of cytosolic Ca2+ in cell injury, necrosis and apoptosis. Curr. Opin. Cell Biol. 4, 227\u2013232 (1992).","journal-title":"Curr. Opin. Cell Biol."},{"key":"79479_CR44","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.fct.2016.04.011","volume":"92","author":"Q Sun","year":"2016","unstructured":"Sun, Q. et al. Fipronil promotes adipogenesis via AMPKalpha-mediated pathway in 3T3-L1 adipocytes. Food Chem. Toxicol. 92, 217\u2013223. https:\/\/doi.org\/10.1016\/j.fct.2016.04.011 (2016).","journal-title":"Food Chem. Toxicol."},{"key":"79479_CR45","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.fct.2016.04.011","volume":"92","author":"Q Sun","year":"2016","unstructured":"Sun, Q. et al. Fipronil promotes adipogenesis via AMPK\u03b1-mediated pathway in 3T3-L1 adipocytes. Food Chem. Toxicol. 92, 217\u2013223 (2016).","journal-title":"Food Chem. Toxicol."},{"key":"79479_CR46","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1530\/EJE-10-1195","volume":"164","author":"X Terra","year":"2011","unstructured":"Terra, X. et al. FABP 4 is associated with inflammatory markers and metabolic syndrome in morbidly obese women. Eur. J. Endocrinol. 164, 539\u2013547 (2011).","journal-title":"Eur. J. Endocrinol."},{"key":"79479_CR47","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1016\/j.nano.2015.05.001","volume":"11","author":"A Rocca","year":"2015","unstructured":"Rocca, A. et al. Pilot in vivo investigation of cerium oxide nanoparticles as a novel anti-obesity pharmaceutical formulation. Nanomed. Nanotechnol. Biol. Med. 11, 1725\u20131734 (2015).","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"79479_CR48","first-page":"1159","volume":"11","author":"A Arya","year":"2016","unstructured":"Arya, A. et al. Cerium oxide nanoparticles promote neurogenesis and abrogate hypoxia-induced memory impairment through AMPK\u2013PKC\u2013CBP signaling cascade. Int. J. Nanomed. 11, 1159 (2016).","journal-title":"Int. J. Nanomed."},{"key":"79479_CR49","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1006\/bbrc.2001.5484","volume":"286","author":"SA Habinowski","year":"2001","unstructured":"Habinowski, S. A. & Witters, L. A. The effects of AICAR on adipocyte differentiation of 3T3-L1 cells. Biochem. Biophys. Res. Commun. 286, 852\u2013856 (2001).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"79479_CR50","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1038\/415339a","volume":"415","author":"Y Minokoshi","year":"2002","unstructured":"Minokoshi, Y. et al. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 415, 339\u2013343. https:\/\/doi.org\/10.1038\/415339a (2002).","journal-title":"Nature"},{"key":"79479_CR51","doi-asserted-by":"publisher","first-page":"25250","DOI":"10.1074\/jbc.M414222200","volume":"280","author":"M Daval","year":"2005","unstructured":"Daval, M. et al. Anti-lipolytic action of AMP-activated protein kinase in rodent adipocytes. J. Biol. Chem. 280, 25250\u201325257 (2005).","journal-title":"J. Biol. Chem."},{"key":"79479_CR52","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1016\/j.biopha.2017.03.099","volume":"90","author":"N Kobyliak","year":"2017","unstructured":"Kobyliak, N. et al. Cerium dioxide nanoparticles possess anti-inflammatory properties in the conditions of the obesity-associated NAFLD in rats. Biomed. Pharmacother. 90, 608\u2013614. https:\/\/doi.org\/10.1016\/j.biopha.2017.03.099 (2017).","journal-title":"Biomed. Pharmacother."},{"key":"79479_CR53","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.molmet.2014.02.002","volume":"3","author":"S Kersten","year":"2014","unstructured":"Kersten, S. Integrated physiology and systems biology of PPAR\u03b1. Mol. Metab. 3, 354\u2013371 (2014).","journal-title":"Mol. Metab."},{"key":"79479_CR54","doi-asserted-by":"publisher","first-page":"28918","DOI":"10.1074\/jbc.M910350199","volume":"275","author":"T Hashimoto","year":"2000","unstructured":"Hashimoto, T. et al. Defect in peroxisome proliferator-activated receptor \u03b1-inducible fatty acid oxidation determines the severity of hepatic steatosis in response to fasting. J. Biol. Chem. 275, 28918\u201328928 (2000).","journal-title":"J. Biol. Chem."},{"key":"79479_CR55","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1016\/j.cell.2006.06.049","volume":"126","author":"AL Bookout","year":"2006","unstructured":"Bookout, A. L. et al. Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network. Cell 126, 789\u2013799 (2006).","journal-title":"Cell"},{"key":"79479_CR56","doi-asserted-by":"publisher","first-page":"4195","DOI":"10.1210\/endo.142.10.8458","volume":"142","author":"P Escher","year":"2001","unstructured":"Escher, P. et al. Rat PPARs: quantitative analysis in adult rat tissues and regulation in fasting and refeeding. Endocrinology 142, 4195\u20134202 (2001).","journal-title":"Endocrinology"},{"key":"79479_CR57","doi-asserted-by":"publisher","first-page":"1508","DOI":"10.1210\/en.2005-1132","volume":"147","author":"D Patsouris","year":"2006","unstructured":"Patsouris, D., Reddy, J. K., M\u00fcller, M. & Kersten, S. Peroxisome proliferator-activated receptor \u03b1 mediates the effects of high-fat diet on hepatic gene expression. Endocrinology 147, 1508\u20131516 (2006).","journal-title":"Endocrinology"},{"key":"79479_CR58","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.gene.2004.06.015","volume":"340","author":"S Kim","year":"2004","unstructured":"Kim, S. et al. Hepatic gene expression profiles in a long-term high-fat diet-induced obesity mouse model. Gene 340, 99\u2013109 (2004).","journal-title":"Gene"},{"key":"79479_CR59","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1155\/2012\/757803","volume":"2012","author":"M Peyrou","year":"2012","unstructured":"Peyrou, M., Ramadori, P., Bourgoin, L. & Foti, M. PPARs in liver diseases and cancer: epigenetic regulation by MicroRNAs. PPAR Res. 2012, 16. https:\/\/doi.org\/10.1155\/2012\/757803 (2012).","journal-title":"PPAR Res."},{"key":"79479_CR60","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1007\/s00018-003-3216-3","volume":"61","author":"S Mandard","year":"2004","unstructured":"Mandard, S., Muller, M. & Kersten, S. Peroxisome proliferator-activated receptor alpha target genes. Cell. Mol. Life Sci. 61, 393\u2013416. https:\/\/doi.org\/10.1007\/s00018-003-3216-3 (2004).","journal-title":"Cell. Mol. Life Sci."},{"key":"79479_CR61","doi-asserted-by":"publisher","first-page":"9967","DOI":"10.1038\/s41598-017-10524-6","volume":"7","author":"Q Zhao","year":"2017","unstructured":"Zhao, Q., Yang, R., Wang, J., Hu, D.-D. & Li, F. PPAR\u03b1 activation protects against cholestatic liver injury. Sci. Rep. 7, 9967. https:\/\/doi.org\/10.1038\/s41598-017-10524-6 (2017).","journal-title":"Sci. Rep."},{"key":"79479_CR62","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/j.jhep.2015.10.020","volume":"64","author":"D Oro","year":"2016","unstructured":"Oro, D. et al. Cerium oxide nanoparticles reduce steatosis, portal hypertension and display anti-inflammatory properties in rats with liver fibrosis. J. Hepatol. 64, 691\u2013698. https:\/\/doi.org\/10.1016\/j.jhep.2015.10.020 (2016).","journal-title":"J. Hepatol."},{"key":"79479_CR63","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1007\/978-1-4419-9072-3_22","volume-title":"Peroxisomal Disorders and Regulation of Genes","author":"WV Berghe","year":"2003","unstructured":"Berghe, W. V. et al. Peroxisomal Disorders and Regulation of Genes 181\u2013196 (Springer, New York, 2003)."},{"key":"79479_CR64","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1007\/s12640-009-9065-6","volume":"16","author":"MA Ortiz-Ortiz","year":"2009","unstructured":"Ortiz-Ortiz, M. A. et al. Nitric oxide-mediated toxicity in paraquat-exposed SH-SY5Y cells: a protective role of 7-nitroindazole. Neurotox. Res. 16, 160\u2013173 (2009).","journal-title":"Neurotox. Res."},{"key":"79479_CR65","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1007\/s10616-014-9779-z","volume":"68","author":"MM Abdel-Daim","year":"2016","unstructured":"Abdel-Daim, M. M. Synergistic protective role of ceftriaxone and ascorbic acid against subacute diazinon-induced nephrotoxicity in rats. Cytotechnology 68, 279\u2013289 (2016).","journal-title":"Cytotechnology"},{"key":"79479_CR66","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1590\/S1516-89132015060298","volume":"58","author":"M Guelfi","year":"2015","unstructured":"Guelfi, M., Maioli, M. A., Tavares, M. A. & Mingatto, F. E. Citotoxicity of fipronil on hepatocytes isolated from rat and effects of its biotransformation. Braz. Arch. Biol. Technol. 58, 843\u2013853 (2015).","journal-title":"Braz. Arch. Biol. Technol."},{"key":"79479_CR67","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1515\/aiht-2017-68-2989","volume":"68","author":"S Karami-Mohajeri","year":"2017","unstructured":"Karami-Mohajeri, S., Ahmadipour, A., Rahimi, H.-R. & Abdollahi, M. Adverse effects of organophosphorus pesticides on the liver: a brief summary of four decades of research. Arhiv Rada Toksikol. 68, 261\u2013275 (2017).","journal-title":"Arhiv Rada Toksikol."},{"key":"79479_CR68","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.pestbp.2015.01.019","volume":"119","author":"B Zhang","year":"2015","unstructured":"Zhang, B. et al. Fipronil induces apoptosis through caspase-dependent mitochondrial pathways in Drosophila S2 cells. Pestic. Biochem. Physiol. 119, 81\u201389. https:\/\/doi.org\/10.1016\/j.pestbp.2015.01.019 (2015).","journal-title":"Pestic. Biochem. Physiol."},{"key":"79479_CR69","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1111\/j.1440-1797.2012.01572.x","volume":"17","author":"DM Small","year":"2012","unstructured":"Small, D. M., Coombes, J. S., Bennett, N., Johnson, D. W. & Gobe, G. C. Oxidative stress, anti-oxidant therapies and chronic kidney disease. Nephrology 17, 311\u2013321. https:\/\/doi.org\/10.1111\/j.1440-1797.2012.01572.x (2012).","journal-title":"Nephrology"},{"key":"79479_CR70","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1177\/0192623309356453","volume":"38","author":"JE Klaunig","year":"2010","unstructured":"Klaunig, J. E., Kamendulis, L. M. & Hocevar, B. A. Oxidative stress and oxidative damage in carcinogenesis. Toxicol. Pathol. 38, 96\u2013109. https:\/\/doi.org\/10.1177\/0192623309356453 (2010).","journal-title":"Toxicol. Pathol."},{"key":"79479_CR71","first-page":"141","volume":"10","author":"M Abdollahi","year":"2004","unstructured":"Abdollahi, M., Ranjbar, A., Shadnia, S., Nikfar, S. & Rezaiee, A. Pesticides and oxidative stress: A review. Med. Sci. Monit. 10, 141\u2013147 (2004).","journal-title":"Med. Sci. Monit."},{"key":"79479_CR72","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1093\/mutage\/geu038","volume":"29","author":"M Kumari","year":"2014","unstructured":"Kumari, M., Kumari, S. I. & Grover, P. Genotoxicity analysis of cerium oxide micro and nanoparticles in Wistar rats after 28 days of repeated oral administration. Mutagenesis 29, 467\u2013479 (2014).","journal-title":"Mutagenesis"},{"key":"79479_CR73","doi-asserted-by":"publisher","first-page":"3479","DOI":"10.3390\/molecules25153479","volume":"25","author":"H Saleh","year":"2020","unstructured":"Saleh, H. et al. Chemo-protective potential of cerium oxide nanoparticles against fipronil-induced oxidative stress, apoptosis, inflammation and reproductive dysfunction in male white albino rats. Molecules 25, 3479 (2020).","journal-title":"Molecules"},{"key":"79479_CR74","doi-asserted-by":"publisher","first-page":"4950","DOI":"10.1039\/c2nr30406f","volume":"4","author":"T Naganuma","year":"2012","unstructured":"Naganuma, T. & Traversa, E. Stability of the Ce 3+ valence state in cerium oxide nanoparticle layers. Nanoscale 4, 4950\u20134953 (2012).","journal-title":"Nanoscale"},{"key":"79479_CR75","doi-asserted-by":"publisher","first-page":"133113","DOI":"10.1063\/1.2061873","volume":"87","author":"S Deshpande","year":"2005","unstructured":"Deshpande, S., Patil, S., Kuchibhatla, S. V. & Seal, S. Size dependency variation in lattice parameter and valency states in nanocrystalline cerium oxide. Appl. Phys. Lett. 87, 133113 (2005).","journal-title":"Appl. Phys. Lett."},{"key":"79479_CR76","doi-asserted-by":"publisher","first-page":"2848","DOI":"10.1002\/smll.200901048","volume":"5","author":"SM Hirst","year":"2009","unstructured":"Hirst, S. M. et al. Anti-inflammatory properties of cerium oxide nanoparticles. Small 5, 2848\u20132856 (2009).","journal-title":"Small"},{"key":"79479_CR77","volume-title":"Cerium Dioxide Nanoparticles Possess Anti-inflammatory Properties in the Conditions of the Obesity-Associated NAFLD in Rats","author":"N Kobyliak","year":"2017","unstructured":"Kobyliak, N. et al. Cerium Dioxide Nanoparticles Possess Anti-inflammatory Properties in the Conditions of the Obesity-Associated NAFLD in Rats Vol. 90 (Springer, New York, 2017)."},{"key":"79479_CR78","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1159\/000282083","volume":"28","author":"H Tilg","year":"2010","unstructured":"Tilg, H. The role of cytokines in non-alcoholic fatty liver disease. Dig. Dis. 28, 179\u2013185 (2010).","journal-title":"Dig. Dis."},{"key":"79479_CR79","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1136\/gutjnl-2015-310798","volume":"65","author":"A Montagner","year":"2016","unstructured":"Montagner, A. et al. Liver PPAR\u03b1 is crucial for whole-body fatty acid homeostasis and is protective against NAFLD. Gut 65, 1202\u20131214. https:\/\/doi.org\/10.1136\/gutjnl-2015-310798 (2016).","journal-title":"Gut"},{"key":"79479_CR80","first-page":"27","volume":"36","author":"WB Salt","year":"2004","unstructured":"Salt, W. B. Nonalcoholic fatty liver disease (NAFLD): A comprehensive review. J. Insurance Med. 36, 27\u201341 (2004).","journal-title":"J. Insurance Med."},{"key":"79479_CR81","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1177\/011542650702200101","volume":"22","author":"S Saadeh","year":"2007","unstructured":"Saadeh, S. Nonalcoholic fatty liver disease and obesity. Nutr. Clin. Pract. 22, 1\u201310 (2007).","journal-title":"Nutr. Clin. Pract."},{"key":"79479_CR82","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1016\/S0016-5085(98)70599-2","volume":"114","author":"CP Day","year":"1998","unstructured":"Day, C. P. & James, O. F. W. Steatohepatitis: A tale of two & #x201c;hits\u201d?. Gastroenterology 114, 842\u2013845. https:\/\/doi.org\/10.1016\/S0016-5085(98)70599-2 (1998).","journal-title":"Gastroenterology"},{"key":"79479_CR83","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1016\/j.jhep.2007.09.009","volume":"48","author":"JP Allard","year":"2008","unstructured":"Allard, J. P. et al. Nutritional assessment and hepatic fatty acid composition in non-alcoholic fatty liver disease (NAFLD): a cross-sectional study. J. Hepatol. 48, 300\u2013307. https:\/\/doi.org\/10.1016\/j.jhep.2007.09.009 (2008).","journal-title":"J. Hepatol."},{"key":"79479_CR84","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5152\/etd.2018.0016","volume":"40","author":"FT Amiri","year":"2018","unstructured":"Amiri, F. T., Hamzeh, M., Beklar, S. Y. & Hosseinimehr, S. J. Anti-apoptotic and antioxidant effect of cerium oxide nanoparticles on cyclophosphamide-induced hepatotoxicity. Erciyes Med. J. 40, 1\u20132 (2018).","journal-title":"Erciyes Med. J."},{"key":"79479_CR85","doi-asserted-by":"publisher","first-page":"101","DOI":"10.3748\/wjg.v3.i2.101","volume":"3","author":"D Wang","year":"1997","unstructured":"Wang, D., Shi, J. Q. & Liu, F. X. Immunohistochemical detection of proliferating cell nuclear antigen in hepatocellular carcinoma. World J. Gastroenterol. 3, 101\u2013103. https:\/\/doi.org\/10.3748\/wjg.v3.i2.101 (1997).","journal-title":"World J. Gastroenterol."},{"key":"79479_CR86","doi-asserted-by":"publisher","first-page":"C1083","DOI":"10.1152\/ajpcell.00381.2005","volume":"290","author":"Y Tian","year":"2006","unstructured":"Tian, Y., Kelemen, S. E. & Autieri, M. V. Inhibition of AIF-1 expression by constitutive siRNA expression reduces macrophage migration, proliferation, and signal transduction initiated by atherogenic stimuli. Am. J. Physiol. Cell Physiol. 290, C1083-1091. https:\/\/doi.org\/10.1152\/ajpcell.00381.2005 (2006).","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"79479_CR87","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1084\/jem.154.6.1899","volume":"154","author":"Y Takasaki","year":"1981","unstructured":"Takasaki, Y., Deng, J.-S. & Tan, E. M. A nuclear antigen associated with cell proliferation and blast transformation. J. Exp. Med. 154, 1899\u20131909 (1981).","journal-title":"J. Exp. Med."},{"key":"79479_CR88","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.2174\/1381612053764896","volume":"11","author":"Y Lee","year":"2005","unstructured":"Lee, Y., Rodriguez, C. & Dionne, R. A. The role of COX-2 in acute pain and the use of selective COX-2 inhibitors for acute pain relief. Curr. Pharm. Des. 11, 1737\u20131755 (2005).","journal-title":"Curr. Pharm. Des."},{"key":"79479_CR89","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1038\/oby.2001.16","volume":"9","author":"JL Miner","year":"2001","unstructured":"Miner, J. L., Cederberg, C. A., Nielsen, M. K., Chen, X. & Baile, C. A. Conjugated linoleic acid (CLA), body fat, and apoptosis. Obes. Res. 9, 129\u2013134 (2001).","journal-title":"Obes. Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-79479-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-79479-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-79479-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T02:02:03Z","timestamp":1670032923000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-79479-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,14]]},"references-count":89,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["79479"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-79479-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,14]]},"assertion":[{"value":"16 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 December 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1310"}}