{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T22:09:25Z","timestamp":1785362965767,"version":"3.55.0"},"reference-count":33,"publisher":"Japanese Society of Toxicologic Pathology","issue":"1","funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K06415"],"award-info":[{"award-number":["20K06415"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Toxicol Pathol"],"published-print":{"date-parts":[[2026]]},"DOI":"10.1293\/tox.2024-0104","type":"journal-article","created":{"date-parts":[[2025,7,20]],"date-time":"2025-07-20T22:07:09Z","timestamp":1753049229000},"page":"3-14","source":"Crossref","is-referenced-by-count":1,"title":["Influence of rapamycin and chloroquine on chemically-induced liver injury in          rats"],"prefix":"10.1293","volume":"39","author":[{"given":"Sho","family":"Fujiwara","sequence":"first","affiliation":[{"name":"Laboratory of Veterinary Pathology, Osaka Metropolitan University, 1-58              Rinku-Orai-Kita, Izumisano, Osaka 598-8531, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Izawa","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Osaka Metropolitan University, 1-58              Rinku-Orai-Kita, Izumisano, Osaka 598-8531, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mutsuki","family":"Mori","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Osaka Metropolitan University, 1-58              Rinku-Orai-Kita, Izumisano, Osaka 598-8531, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuru","family":"Kuwamura","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Osaka Metropolitan University, 1-58              Rinku-Orai-Kita, Izumisano, Osaka 598-8531, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"121","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1.  Hoofnagle              JH, and                Bj\u00f6rnsson              ES.            Drug-induced liver injury\u2014types and phenotypes. N            Engl J Med. 381: 264\u2013273.            2019.","DOI":"10.1056\/NEJMra1816149"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2.  Alempijevic              T,                Zec              S, and                Milosavljevic              T. Drug-induced            liver injury: do we know everything?          World J Hepatol. 9:            491\u2013502. 2017.","DOI":"10.4254\/wjh.v9.i10.491"},{"key":"3","doi-asserted-by":"publisher","unstructured":"3.  Sgro              C,                Clinard              F,                Ouazir              K,                Chanay              H,                Allard              C,                Guilleminet              C,                Lenoir              C,                Lemoine              A, and                Hillon              P. Incidence of            drug-induced hepatic injuries: a French population-based study.            Hepatology. 36: 451\u2013455.            2002.","DOI":"10.1053\/jhep.2002.34857"},{"key":"4","doi-asserted-by":"publisher","unstructured":"4.  Bj\u00f6rnsson              ES,                Bergmann              OM,                Bj\u00f6rnsson              HK,                Kvaran              RB, and                Olafsson              S. Incidence,            presentation, and outcomes in patients with drug-induced liver injury in the general            population of Iceland. Gastroenterology.          144: 1419\u20131425, 1425.e1\u20131425.e3, quiz            e19\u2013e20. 2013.","DOI":"10.1053\/j.gastro.2013.02.006"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5.  Glick              D,                Barth              S, and                Macleod              KF. Autophagy:            cellular and molecular mechanisms. J Pathol.            221: 3\u201312. 2010.","DOI":"10.1002\/path.2697"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6.  Mizushima              N. Autophagy:            process and function. Genes Dev. 21:            2861\u20132873. 2007.","DOI":"10.1101\/gad.1599207"},{"key":"7","doi-asserted-by":"publisher","unstructured":"7.  Wang              K. Autophagy            and apoptosis in liver injury. Cell Cycle.            14: 1631\u20131642. 2015.","DOI":"10.1080\/15384101.2015.1038685"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8.  Qian              H,                Chao              X,                Williams              J,                Fulte              S,                Li              T,                Yang              L, and                Ding              WX. Autophagy            in liver diseases: a review. Mol Aspects Med.            82: 100973. 2021.","DOI":"10.1016\/j.mam.2021.100973"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9.  Liu              T,                Zhang              J,                Li              K,                Deng              L, and                Wang              H. Combination            of an autophagy inducer and an autophagy inhibitor: a smarter strategy emerging in            cancer therapy. Front Pharmacol. 11:            408. 2020.","DOI":"10.3389\/fphar.2020.00408"},{"key":"10","doi-asserted-by":"publisher","unstructured":"10.  Ni              HM,                Bockus              A,                Boggess              N,                Jaeschke              H, and                Ding              WX. Activation            of autophagy protects against acetaminophen-induced hepatotoxicity.            Hepatology. 55: 222\u2013232.            2012.","DOI":"10.1002\/hep.24690"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11.  Ding              WX,                Li              M,                Chen              X,                Ni              HM,                Lin              CW,                Gao              W,                Lu              B,                Stolz              DB,                Clemens              DL, and                Yin              XM. Autophagy            reduces acute ethanol-induced hepatotoxicity and steatosis in mice.            Gastroenterology. 139:            1740\u20131752. 2010.","DOI":"10.1053\/j.gastro.2010.07.041"},{"key":"12","doi-asserted-by":"publisher","unstructured":"12.  Mori              M,                Izawa              T,                Inai              Y,                Fujiwara              S,                Aikawa              R,                Kuwamura              M, and                Yamate              J. Dietary iron            overload differentially modulates chemically-induced liver injury in            rats. Nutrients. 12:            2784. 2020.","DOI":"10.3390\/nu12092784"},{"key":"13","doi-asserted-by":"publisher","unstructured":"13.  Atarashi              M,                Izawa              T,                Mori              M,                Inai              Y,                Kuwamura              M, and                Yamate              J. Dietary iron            overload abrogates chemically-induced liver cirrhosis in rats.            Nutrients. 10: 1400. 2018.","DOI":"10.3390\/nu10101400"},{"key":"14","doi-asserted-by":"publisher","unstructured":"14.  Mizushima              N, and                Yoshimori              T. How to            interpret LC3 immunoblotting. Autophagy.            3: 542\u2013545. 2007.","DOI":"10.4161\/auto.4600"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15.  Dai              C,                Xiao              X,                Li              D,                Tun              S,                Wang              Y,                Velkov              T, and                Tang              S. Chloroquine            ameliorates carbon tetrachloride-induced acute liver injury in mice via the concomitant            inhibition of inflammation and induction of apoptosis. Cell            Death Dis. 9: 1164. 2018.","DOI":"10.1038\/s41419-018-1136-2"},{"key":"16","doi-asserted-by":"publisher","unstructured":"16.  Mizushima              N,                Yoshimori              T, and                Levine              B. Methods in            mammalian autophagy research. Cell.            140: 313\u2013326. 2010.","DOI":"10.1016\/j.cell.2010.01.028"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17.  Song              YM,                Song              SO,                Jung              YK,                Kang              ES,                Cha              BS,                Lee              HC, and                Lee              BW. Dimethyl            sulfoxide reduces hepatocellular lipid accumulation through autophagy            induction. Autophagy. 8:            1085\u20131097. 2012.","DOI":"10.4161\/auto.20260"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18.  Recknagel              RO,                Glende                  EA Jr,           Dolak              JA, and                Waller              RL. Mechanisms            of carbon tetrachloride toxicity. Pharmacol Ther.            43: 139\u2013154. 1989.","DOI":"10.1016\/0163-7258(89)90050-8"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19.  Scholten              D,                Trebicka              J,                Liedtke              C, and                Weiskirchen              R. The carbon            tetrachloride model in mice. Lab Anim.            49(Suppl): 4\u201311.            2015.","DOI":"10.1177\/0023677215571192"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20.  Dunlop              EA, and                Tee              AR. Mammalian            target of rapamycin complex 1: signalling inputs, substrates and feedback            mechanisms. Cell Signal. 21:            827\u2013835. 2009.","DOI":"10.1016\/j.cellsig.2009.01.012"},{"key":"21","doi-asserted-by":"publisher","unstructured":"21.  Laplante              M, and                Sabatini              DM. mTOR            signaling in growth control and disease. Cell.            149: 274\u2013293. 2012.","DOI":"10.1016\/j.cell.2012.03.017"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22.  Mart\u00ednez-Cisuelo              V,                G\u00f3mez              J,                Garc\u00eda-Junceda              I,                Naud\u00ed              A,                Cabr\u00e9              R,                Mota-Martorell              N,                L\u00f3pez-Torres              M,                Gonz\u00e1lez-S\u00e1nchez              M,                Pamplona              R, and                Barja              G. Rapamycin            reverses age-related increases in mitochondrial ROS production at complex I, oxidative            stress, accumulation of mtDNA fragments inside nuclear DNA, and lipofuscin level, and            increases autophagy, in the liver of middle-aged mice. Exp            Gerontol. 83: 130\u2013138.            2016.","DOI":"10.1016\/j.exger.2016.08.002"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23.  Jiang              J,                Jiang              J,                Zuo              Y, and                Gu              Z. Rapamycin            protects the mitochondria against oxidative stress and apoptosis in a rat model of            Parkinson\u2019s disease. Int J Mol Med.          31: 825\u2013832. 2013.","DOI":"10.3892\/ijmm.2013.1280"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24.  Li              YN,                Sun              FF,                Ouyang              F,                Luo              D,                Zhang              ZX,                Lu              MX,                Hu              CY,                Shi              YH,                Gui              Q,                Zhang              JY, and                Yang              TS. Alterations            in liver triglyceride profiles in CCl<sub>4<\/sub>-induced liver            regeneration. Biochem Biophys Res Commun.            734: 150662. 2024.","DOI":"10.1016\/j.bbrc.2024.150662"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25.  Chen              H. Nutrient            mTORC1 signaling contributes to hepatic lipid metabolism in the pathogenesis of            non-alcoholic fatty liver disease. Liver Res.            4: 15\u201322. 2020.","DOI":"10.1016\/j.livres.2020.02.004"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26.  den                Hartigh              LJ,                Goodspeed              L,                Wang              SA,                Kenerson              HL,                Omer              M,                O\u2019Brien              KD,                Ladiges              W,                Yeung              R, and                Subramanian              S. Chronic oral            rapamycin decreases adiposity, hepatic triglycerides and insulin resistance in male mice            fed a diet high in sucrose and saturated fat. Exp            Physiol. 103: 1469\u20131480.            2018.","DOI":"10.1113\/EP087207"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27.  Wu              Y,                He              X,                Chen              H,                Lin              Y,                Zheng              C, and                Zheng              B. Extraction            and characterization of hepatoprotective polysaccharides from Anoectochilus roxburghii            against CCl<sub>4<\/sub>-induced liver injury via regulating lipid metabolism and the gut            microbiota. Int J Biol Macromol. 277:            134305. 2024.","DOI":"10.1016\/j.ijbiomac.2024.134305"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28.  Yamamoto              M,                Kensler              TW, and                Motohashi              H. The            KEAP1-NRF2 system: a THIOL-based sensor-effector apparatus for maintaining redox            homeostasis. Physiol Rev. 98:            1169\u20131203. 2018.","DOI":"10.1152\/physrev.00023.2017"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29.  Komatsu              M,                Kurokawa              H,                Waguri              S,                Taguchi              K,                Kobayashi              A,                Ichimura              Y,                Sou              YS,                Ueno              I,                Sakamoto              A,                Tong              KI,                Kim              M,                Nishito              Y,                Iemura              S,                Natsume              T,                Ueno              T,                Kominami              E,                Motohashi              H,                Tanaka              K, and                Yamamoto              M. The            selective autophagy substrate p62 activates the stress responsive transcription factor            Nrf2 through inactivation of Keap1. Nat Cell Biol.            12: 213\u2013223. 2010.","DOI":"10.1038\/ncb2021"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30.  Chen              M,                Huang              W,                Wang              C,                Nie              H,                Li              G,                Sun              T,                Yang              F,                Zhang              Y,                Shu              K,                Wang              C, and                Gong              Q.            High-mobility group box 1 exacerbates CCl<sub>4<\/sub>-induced acute liver            injury in mice. Clin Immunol. 153:            56\u201363. 2014.","DOI":"10.1016\/j.clim.2014.03.021"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31.  Brki\u0107              BM,                Rov\u010danin              B,                Stojanovi\u0107              M,                Srebro              D,                Vu\u010dkovi\u0107              S, and                Savi\u0107 Vujovi\u0107              K. Chloroquine            attenuates oxidative stress in gentamicin-induced nephrotoxicity in          rats. Dose Response. 20:            15593258221119871. 2022.","DOI":"10.1177\/15593258221119871"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32.  Chen              S,                Melchior                  WB Jr,           Wu              Y, and                Guo              L. Autophagy in            drug-induced liver toxicity. Yao Wu Shi Pin Fen Xi.            22: 161\u2013168. 2014.","DOI":"10.1016\/j.jfda.2014.03.007"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33.  Klinger              W,                Devereux              T,                Maronpot              R, and                Fouts              J. Functional            hepatocellular heterogeneity determined by the hepatotoxins allyl alcohol and            bromobenzene in immature and adult Fischer 344 rats. Toxicol            Appl Pharmacol. 83: 108\u2013114.            1986.","DOI":"10.1016\/0041-008X(86)90328-5"}],"container-title":["Journal of Toxicologic Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/tox\/39\/1\/39_2024-0104\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T04:39:39Z","timestamp":1768624779000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/tox\/39\/1\/39_2024-0104\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":33,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.1293\/tox.2024-0104","relation":{},"ISSN":["0914-9198","1881-915X"],"issn-type":[{"value":"0914-9198","type":"print"},{"value":"1881-915X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026]]},"article-number":"2024-0104"}}