{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T06:24:00Z","timestamp":1789885440981,"version":"4.0.1"},"reference-count":41,"publisher":"Japanese Society of Toxicology","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Toxicol. Sci."],"published-print":{"date-parts":[[2018]]},"DOI":"10.2131\/jts.43.611","type":"journal-article","created":{"date-parts":[[2018,10,4]],"date-time":"2018-10-04T18:32:18Z","timestamp":1538677938000},"page":"611-621","source":"Crossref","is-referenced-by-count":13,"title":["Differential impacts of mineralocorticoid receptor antagonist potassium canrenoate on liver and renal changes in high fat diet-mediated early hepatocarcinogenesis model rats"],"prefix":"10.2131","volume":"43","author":[{"given":"Misato","family":"Nakamura","sequence":"first","affiliation":[{"name":"Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayumi","family":"Eguchi","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Inohana","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rei","family":"Nagahara","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotada","family":"Murayama","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Kawashima","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayaka","family":"Mizukami","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology"},{"name":"Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihoko","family":"Koyanagi","sequence":"additional","affiliation":[{"name":"Global Scientific and Regulatory Affairs, San-Ei Gen F. F. I., Inc."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shim-mo","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Global Scientific and Regulatory Affairs, San-Ei Gen F. F. I., Inc."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert R.","family":"Maronpot","sequence":"additional","affiliation":[{"name":"Maronpot Consulting LLC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Shibutani","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshinori","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"898","reference":[{"key":"1","first-page":"98","year":"2010","unstructured":"Angeli, P., Fasolato, S., Mazza, E., Okolicsanyi, L., Maresio, G., Velo, E., Galioto, A., Salinas, F., D\u2019Aquino, M., Sticca, A. and Gatta, A. (2010): Combined versus sequential diuretic treatment of ascites in non-azotaemic patients with cirrhosis: results of an open randomised clinical trial. Gut, <b>59<\/b>, 98-104.","journal-title":"Gut","ISSN":"https:\/\/id.crossref.org\/issn\/0017-5749","issn-type":"print"},{"key":"2","doi-asserted-by":"crossref","unstructured":"Aranda, M., Albendea, C.D., Lostal\u00e9, F., L\u00f3pez-Pingarr\u00f3n, L., Fuentes-Broto, L., Mart\u00ednez-Ballar\u00edn, E., Reiter, R.J., P\u00e9rez-Castej\u00f3n, M.C. and Garc\u00eda, J.J. (2010): In vivo hepatic oxidative stress because of carbon tetrachloride toxicity: protection by melatonin and pinoline. J. Pineal Res., <b>49<\/b>, 78-85.","DOI":"10.1111\/j.1600-079X.2010.00769.x"},{"key":"3","doi-asserted-by":"crossref","unstructured":"Bolondi, L., Piscaglia, F., Gatta, A., Salerno, F., Bernardi, M., Ascione, A., Ferra\u00f9, O., Sacerdoti, D., Visentin, S., Trevisani, F., Mazzanti, R., Donati, G., Arena, U., Gentilini, P. and Group, D.O.; DOC (Decrease Of Complications in cirrhosis) Study Group. (2006): Effect of potassium canrenoate, an anti-aldosterone agent, on incidence of ascites and variceal progression in cirrhosis. Clin. Gastroenterol. Hepatol., <b>4<\/b>, 1395-1402.","DOI":"10.1016\/j.cgh.2006.06.005"},{"key":"4","doi-asserted-by":"crossref","unstructured":"Bos, R., Mougenot, N., M\u00e9diani, O., Vanhoutte, P.M. and Lechat, P. (2004): Potassium canrenoate, an aldosterone receptor antagonist, reduces isoprenaline-induced cardiac fibrosis in the rat. J. Pharmacol. Exp. Ther., <b>309<\/b>, 1160-1166.","DOI":"10.1124\/jpet.103.063388"},{"key":"5","doi-asserted-by":"crossref","unstructured":"Brambilla, G. and Martelli, A. (2002): Are some progestins genotoxic liver carcinogens? Mutat. Res., <b>512<\/b>, 155-163.","DOI":"10.1016\/S1383-5742(02)00047-9"},{"key":"6","doi-asserted-by":"publisher","unstructured":"Bugianesi, E., McCullough, A.J. and Marchesini, G. (2005): Insulin resistance: a metabolic pathway to chronic liver disease. Hepatology, <b>42<\/b>, 987-1000.","DOI":"10.1002\/hep.20920"},{"key":"7","doi-asserted-by":"crossref","unstructured":"Catalogna, M., Fishman, S., Halpern, Z., Ben-Shlomo, S., Nevo, U. and Ben-Jacob, E. (2016): Regulation of glucose dynamics by noninvasive peripheral electrical stimulation in normal and insulin-resistant rats. Metabolism, <b>65<\/b>, 863-873.","DOI":"10.1016\/j.metabol.2016.03.004"},{"key":"8","doi-asserted-by":"crossref","unstructured":"Chatterjee, S., Ganini, D., Tokar, E.J., Kumar, A., Das, S., Corbett, J., Kadiiska, M.B., Waalkes, M.P., Diehl, A.M. and Mason, R.P. (2013): Leptin is key to peroxynitrite-mediated oxidative stress and Kupffer cell activation in experimental non-alcoholic steatohepatitis. J. Hepatol., <b>58<\/b>, 778-784.","DOI":"10.1016\/j.jhep.2012.11.035"},{"key":"9","doi-asserted-by":"crossref","unstructured":"C\u00f6mert, B., Mas, M.R., Erdem, H., Dinc, A., Saglamkaya, U., Cigerim, M., Kuzhan, O., Unal, T. and Kocabalkan, F. (2001): Insulin resistance in non-alcoholic steatohepatitis. Dig. Liver Dis., <b>33<\/b>, 353-358.","DOI":"10.1016\/S1590-8658(01)80091-8"},{"key":"10","doi-asserted-by":"crossref","unstructured":"Di Meo, S., Reed, T.T., Venditti, P. and Victor, V.M. (2016): Role of ROS and RNS Sources in Physiological and Pathological Conditions. Oxid. Med. Cell. Longev., <b>2016<\/b>, 1245049.","DOI":"10.1155\/2016\/1245049"},{"key":"11","doi-asserted-by":"crossref","unstructured":"Dongiovanni, P., Romeo, S. and Valenti, L. (2014): Hepatocellular carcinoma in nonalcoholic fatty liver: role of environmental and genetic factors. World J. Gastroenterol., <b>20<\/b>, 12945-12955.","DOI":"10.3748\/wjg.v20.i36.12945"},{"key":"12","doi-asserted-by":"crossref","unstructured":"Frazier, K.S., Seely, J.C., Hard, G.C., Betton, G., Burnett, R., Nakatsuji, S., Nishikawa, A., Durchfeld-Meyer, B. and Bube, A. (2012): Proliferative and nonproliferative lesions of the rat and mouse urinary system. Toxicol. Pathol., <b>40<\/b> (Suppl), 14S-86S.","DOI":"10.1177\/0192623312438736"},{"key":"13","doi-asserted-by":"crossref","unstructured":"Hara, S., Morita, R., Ogawa, T., Segawa, R., Takimoto, N., Suzuki, K., Hamadate, N., Hayashi, S.M., Odachi, A., Ogiwara, I., Shibusawa, S., Yoshida, T. and Shibutani, M. (2014): Tumor suppression effects of bilberry extracts and enzymatically modified isoquercitrin in early preneoplastic liver cell lesions induced by piperonyl butoxide promotion in a two-stage rat hepatocarcinogenesis model. Exp. Toxicol. Pathol., <b>66<\/b>, 225-234.","DOI":"10.1016\/j.etp.2014.02.002"},{"key":"14","unstructured":"International Agency for Research on Cancer (IARC). (1999): Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol. 72, Hormonal Contraception and Post-Menopausal Hormonal Therapy, IARC, Lyon, France."},{"key":"15","doi-asserted-by":"crossref","unstructured":"Ito, N., Tamano, S. and Shirai, T. (2003): A medium-term rat liver bioassay for rapid <i>in vivo<\/i> detection of carcinogenic potential of chemicals. Cancer Sci., <b>94<\/b>, 3-8.","DOI":"10.1111\/j.1349-7006.2003.tb01343.x"},{"key":"16","doi-asserted-by":"crossref","unstructured":"Jonassen, T.E., Petersen, J.S., S\u00f8rensen, A.M., Andreasen, F. and Christensen, S. (1998): Aldosterone receptor blockade inhibits increased furosemide-sensitive sodium reabsorption in rats with liver cirrhosis. J. Pharmacol. Exp. Ther., <b>287<\/b>, 931-936.","DOI":"10.1016\/S0022-3565(24)37883-8"},{"key":"17","first-page":"1313","year":"2005","unstructured":"Kleiner, D.E., Brunt, E.M., Van Natta, M., Behling, C., Contos, M.J., Cummings, O.W., Ferrell, L.D., Liu, Y.C., Torbenson, M.S., Unalp-Arida, A., Yeh, M., McCullough, A.J. and Sanyal, A.J.; Nonalcoholic Steatohepatitis Clinical Research Network. (2005): Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology, <b>41<\/b>, 1313-1321.","journal-title":"Hepatology","ISSN":"https:\/\/id.crossref.org\/issn\/0270-9139","issn-type":"print"},{"key":"18","doi-asserted-by":"crossref","unstructured":"Kono, H., Rusyn, I., Yin, M., G\u00e4bele, E., Yamashina, S., Dikalova, A., Kadiiska, M.B., Connor, H.D., Mason, R.P., Segal, B.H., Bradford, B.U., Holland, S.M. and Thurman, R.G. (2000): NADPH oxidase-derived free radicals are key oxidants in alcohol-induced liver disease. J. Clin. Invest., <b>106<\/b>, 867-872.","DOI":"10.1172\/JCI9020"},{"key":"19","doi-asserted-by":"crossref","unstructured":"Liu, W., Baker, R.D., Bhatia, T., Zhu, L. and Baker, S.S. (2016): Pathogenesis of nonalcoholic steatohepatitis. Cell. Mol. Life Sci., <b>73<\/b>, 1969-1987.","DOI":"10.1007\/s00018-016-2161-x"},{"key":"20","doi-asserted-by":"crossref","unstructured":"Livak, K.J. and Schmittgen, T.D. (2001): Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)). Method. Methods, <b>25<\/b>, 402-408.","DOI":"10.1006\/meth.2001.1262"},{"key":"21","doi-asserted-by":"crossref","unstructured":"Lomb\u00e8s, M., Farman, N., Oblin, M.E., Baulieu, E.E., Bonvalet, J.P., Erlanger, B.F. and Gasc, J.M. (1990): Immunohistochemical localization of renal mineralocorticoid receptor by using an anti-idiotypic antibody that is an internal image of aldosterone. Proc. Natl. Acad. Sci. USA, <b>87<\/b>, 1086-1088.","DOI":"10.1073\/pnas.87.3.1086"},{"key":"22","first-page":"917","year":"2003","unstructured":"Marchesini, G., Bugianesi, E., Forlani, G., Cerrelli, F., Lenzi, M., Manini, R., Natale, S., Vanni, E., Villanova, N., Melchionda, N. and Rizzetto, M. (2003): Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology, <b>37<\/b>, 917-923.","journal-title":"Hepatology","ISSN":"https:\/\/id.crossref.org\/issn\/0270-9139","issn-type":"print"},{"key":"23","doi-asserted-by":"crossref","unstructured":"Martelli, A., Carrozzino, R., Mattioli, F., Bucci, G., Lamarino, G. and Brambilla, G. (2002): DNA damage in tissues of rat treated with potassium canrenoate. Toxicology, <b>171<\/b>, 95-103.","DOI":"10.1016\/S0300-483X(01)00562-5"},{"key":"24","doi-asserted-by":"crossref","unstructured":"Martelli, A., Mattioli, F., Carrozzino, R., Ferraris, E., Marchese, M., Angiola, M. and Brambilla, G. (1999): Genotoxicity testing of potassium canrenoate in cultured rat and human cells. Mutagenesis, <b>14<\/b>, 463-472.","DOI":"10.1093\/mutage\/14.5.463"},{"key":"25","doi-asserted-by":"crossref","unstructured":"Nagai, J., Christensen, E.I., Morris, S.M., Willnow, T.E., Cooper, J.A. and Nielsen, R. (2005): Mutually dependent localization of megalin and Dab2 in the renal proximal tubule. Am. J. Physiol. Renal Physiol., <b>289<\/b>, F569-F576.","DOI":"10.1152\/ajprenal.00292.2004"},{"key":"26","doi-asserted-by":"crossref","unstructured":"Nasri, R., Abdelhedi, O., Jemil, I., Daoued, I., Hamden, K., Kallel, C., Elfeki, A., Lamri-Senhadji, M., Boualga, A., Nasri, M. and Karra-Ch\u00e2abouni, M. (2015): Ameliorating effects of goby fish protein hydrolysates on high-fat-high-fructose diet-induced hyperglycemia, oxidative stress and deterioration of kidney function in rats. Chem. Biol. Interact., <b>242<\/b>, 71-80.","DOI":"10.1016\/j.cbi.2015.08.003"},{"key":"27","first-page":"1145","year":"2015","unstructured":"Nie, H., Li, J., Yang, X.M., Cao, Q.Z., Feng, M.X., Xue, F., Wei, L., Qin, W., Gu, J., Xia, Q. and Zhang, Z.G. (2015): Mineralocorticoid receptor suppresses cancer progression and the Warburg effect by modulating the miR-338-3p-PKLR axis in hepatocellular carcinoma. Hepatology, <b>62<\/b>, 1145-1159.","journal-title":"Hepatology","ISSN":"https:\/\/id.crossref.org\/issn\/0270-9139","issn-type":"print"},{"key":"28","doi-asserted-by":"crossref","unstructured":"Nyska, A., Hayashi, S.M., Koyanagi, M., Davis, J.P., Jokinen, M.P., Ramot, Y. and Maronpot, R.R. (2016): Ninety-day toxicity and single-dose toxicokinetics study of alpha-glycosyl isoquercitrin in Sprague-Dawley rats. Food Chem. Toxicol., <b>97<\/b>, 354-366.","DOI":"10.1016\/j.fct.2016.09.030"},{"key":"29","doi-asserted-by":"crossref","unstructured":"Odermatt, A. and Kratschmar, D.V. (2012): Tissue-specific modulation of mineralocorticoid receptor function by 11\u03b2-hydroxysteroid dehydrogenases: an overview. Mol. Cell. Endocrinol., <b>350<\/b>, 168-186.","DOI":"10.1016\/j.mce.2011.07.020"},{"key":"30","doi-asserted-by":"crossref","unstructured":"Ong, G.S. and Young, M.J. (2017): Mineralocorticoid regulation of cell function: the role of rapid signalling and gene transcription pathways. J. Mol. Endocrinol., <b>58<\/b>, R33-R57.","DOI":"10.1530\/JME-15-0318"},{"key":"31","doi-asserted-by":"crossref","unstructured":"Ozaki, K., Mahler, J.F., Haseman, J.K., Moomaw, C.R., Nicolette, M.L. and Nyska, A. (2001): Unique renal tubule changes induced in rats and mice by the peroxisome proliferators 2,4-dichlorophenoxyacetic acid (2,4-D) and WY-14643. Toxicol. Pathol., <b>29<\/b>, 440-450.","DOI":"10.1080\/01926230152499791"},{"key":"32","doi-asserted-by":"crossref","unstructured":"Sanchez-Lazo, L., Brisard, D., Elis, S., Maillard, V., Uzbekov, R., Labas, V., Desmarchais, A., Papillier, P., Monget, P. and Uzbekova, S. (2014): Fatty acid synthesis and oxidation in cumulus cells support oocyte maturation in bovine. Mol. Endocrinol., <b>28<\/b>, 1502-1521.","DOI":"10.1210\/me.2014-1049"},{"key":"33","doi-asserted-by":"crossref","unstructured":"Schuppler, J. and G\u00fcnzel, P. (1979): Liver tumors and steroid hormones in rats and mice. Arch. Toxicol. Suppl., <b>2<\/b>, 181-195.","DOI":"10.1007\/978-3-642-67265-1_16"},{"key":"34","doi-asserted-by":"crossref","unstructured":"Serra, A., Romero, R., Lopez, D., Navarro, M., Esteve, A., Perez, N., Alastrue, A. and Ariza, A. (2008): Renal injury in the extremely obese patients with normal renal function. Kidney Int., <b>73<\/b>, 947-955.","DOI":"10.1038\/sj.ki.5002796"},{"key":"35","doi-asserted-by":"crossref","unstructured":"Shibata, S. (2017): 30 YEARS OF THE MINERALOCORTICOID RECEPTOR: mineralocorticoid receptor and NaCl transport mechanisms in the renal distal nephron. J. Endocrinol., <b>234<\/b>, T35-T47.","DOI":"10.1530\/JOE-16-0669"},{"key":"36","doi-asserted-by":"crossref","unstructured":"Thiesson, H.C., Jensen, B.L., Bistrup, C., Ottosen, P.D., McNeilly, A.D., Andrew, R., Seckl, J. and Sk\u00f8tt, O. (2007): Renal sodium retention in cirrhotic rats depends on glucocorticoid-mediated activation of mineralocorticoid receptor due to decreased renal 11beta-HSD-2 activity. Am. J. Physiol. Regul. Integr. Comp. Physiol., <b>292<\/b>, R625-R636.","DOI":"10.1152\/ajpregu.00418.2005"},{"key":"37","doi-asserted-by":"crossref","unstructured":"Wada, T., Kenmochi, H., Miyashita, Y., Sasaki, M., Ojima, M., Sasahara, M., Koya, D., Tsuneki, H. and Sasaoka, T. (2010): Spironolactone improves glucose and lipid metabolism by ameliorating hepatic steatosis and inflammation and suppressing enhanced gluconeogenesis induced by high-fat and high-fructose diet. Endocrinology, <b>151<\/b>, 2040-2049.","DOI":"10.1210\/en.2009-0869"},{"key":"38","doi-asserted-by":"crossref","unstructured":"Whaley-Connell, A., Johnson, M.S. and Sowers, J.R. (2010): Aldosterone: role in the cardiometabolic syndrome and resistant hypertension. Prog. Cardiovasc. Dis., <b>52<\/b>, 401-409.","DOI":"10.1016\/j.pcad.2009.12.004"},{"key":"39","doi-asserted-by":"crossref","unstructured":"Yoshida, T., Murayama, H., Kawashima, M., Nagahara, R., Kangawa, Y., Mizukami, S., Kimura, M., Abe, H., Hayashi, S.M. and Shibutani, M. (2017): Apocynin and enzymatically modified isoquercitrin suppress the expression of a NADPH oxidase subunit p22phox in steatosis-related preneoplastic liver foci of rats. Exp. Toxicol. Pathol., <b>69<\/b>, 9-16.","DOI":"10.1016\/j.etp.2016.10.003"},{"key":"40","unstructured":"Zang, S.S., Song, A., Liu, Y.X., Wang, C., Song, G.Y., Li, X.L., Zhu, Y.J., Yu, X., Li, L., Liu, C.X., Kang, J.C. and Ren, L.P. (2015): Chinese medicine Jinlida (JLD) ameliorates high-fat-diet induced insulin resistance in rats by reducing lipid accumulation in skeletal muscle. Int. J. Clin. Exp. Med., <b>8<\/b>, 4620-4634."},{"key":"41","doi-asserted-by":"crossref","unstructured":"Zennaro, M.C., Caprio, M. and F\u00e8ve, B. (2009): Mineralocorticoid receptors in the metabolic syndrome. Trends Endocrinol. Metab., <b>20<\/b>, 444-451.","DOI":"10.1016\/j.tem.2009.05.006"}],"container-title":["The Journal of Toxicological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/jts\/43\/10\/43_611\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T15:14:30Z","timestamp":1769526870000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/jts\/43\/10\/43_611\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018]]},"references-count":41,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2018]]}},"URL":"https:\/\/doi.org\/10.2131\/jts.43.611","relation":{},"ISSN":["0388-1350","1880-3989"],"issn-type":[{"value":"0388-1350","type":"print"},{"value":"1880-3989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018]]}}}