{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T05:53:44Z","timestamp":1788587624036,"version":"build-2803163510"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T00:00:00Z","timestamp":1602720000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T00:00:00Z","timestamp":1602720000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Alcohol\u2010associated liver disease (ALD) is a common chronic liver disease worldwide with high morbidity and mortality, and no Food and Drug Administration\u2013approved therapies. Fructose (dietary or endogenous), its metabolite uric acid, and aldose reductase (AR, the only endogenous enzyme that produces fructose) are strongly associated with the development of nonalcoholic fatty liver disease. However, the role of AR or its metabolites in ALD remains understudied and was examined using human specimens, cultured cells, and mouse model systems.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>We demonstrated in liver specimens from patients with alcoholic hepatitis, the AR up\u2010regulation and elevated AR metabolites (sorbitol, fructose, and uric acid), which correlated significantly with (1) increased lipid peroxidation byproducts and endoplasmic reticulum (ER) stress, (2) decreased protective ER chaperones, and (3) greater cell death and liver injury. Furthermore, we established a causal role for AR in ALD by showing that the genetic deficiency of AR (knockout mice) prevented alcohol\u2010induced increase in harmful AR metabolites, toxic aldehydes, steatosis, ER stress, apoptosis, and liver injury. Finally, we demonstrated the therapeutic potential of pharmacological AR inhibition against alcohol\u2010induced hepatic injury in experimental ALD.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our data demonstrate that hepatic AR up\u2010regulation, and consequent elevation in fructose, sorbitol and\/or uric acid, are important factors contributing to alcohol\u2010induced steatosis, ER stress, apoptosis, and liver injury in both experimental and human ALD. Our study provides a strong rationale to evaluate AR as a potential therapeutic target and to test AR inhibitors to ameliorate alcohol\u2010induced liver injury.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31197","type":"journal-article","created":{"date-parts":[[2020,2,22]],"date-time":"2020-02-22T11:35:10Z","timestamp":1582371310000},"page":"1617-1637","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":49,"title":["Elevated Fructose and Uric Acid Through Aldose Reductase Contribute to Experimental and Human Alcoholic Liver Disease"],"prefix":"10.1097","volume":"72","author":[{"given":"Min","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Medicine,University of Louisville,Louisville,KY"},{"name":"Alcohol Research Center,University of Louisville,Louisville,KY"},{"name":"Hepatobiology and Toxicology Center,University of Louisville,Louisville,KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Yang","family":"Chen","sequence":"additional","affiliation":[{"name":"Alcohol Research Center,University of Louisville,Louisville,KY"},{"name":"Department of Pharmacology & Toxicology,University of Louisville,Louisville,KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Louisville,Louisville,KY"},{"name":"Alcohol Research Center,University of Louisville,Louisville,KY"},{"name":"Hepatobiology and Toxicology Center,University of Louisville,Louisville,KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila","family":"Gobejishvili","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Louisville,Louisville,KY"},{"name":"Alcohol Research Center,University of Louisville,Louisville,KY"},{"name":"Hepatobiology and Toxicology Center,University of Louisville,Louisville,KY"},{"name":"Department of Pharmacology & Toxicology,University of Louisville,Louisville,KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirish S.","family":"Barve","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Louisville,Louisville,KY"},{"name":"Alcohol Research Center,University of Louisville,Louisville,KY"},{"name":"Hepatobiology and Toxicology Center,University of Louisville,Louisville,KY"},{"name":"Department of Pharmacology & Toxicology,University of Louisville,Louisville,KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig J.","family":"McClain","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Louisville,Louisville,KY"},{"name":"Alcohol Research Center,University of Louisville,Louisville,KY"},{"name":"Hepatobiology and Toxicology Center,University of Louisville,Louisville,KY"},{"name":"Department of Pharmacology & Toxicology,University of Louisville,Louisville,KY"},{"name":"Robley Rex VAMC,Louisville,KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swati","family":"Joshi\u2010Barve","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Louisville,Louisville,KY"},{"name":"Alcohol Research Center,University of Louisville,Louisville,KY"},{"name":"Hepatobiology and Toxicology Center,University of Louisville,Louisville,KY"},{"name":"Department of Pharmacology & Toxicology,University of Louisville,Louisville,KY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2020,10,15]]},"reference":[{"key":"hep31197-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/s41575-019-0144-8","article-title":"Past, present and future perspectives in nonalcoholic fatty liver disease","volume":"16","year":"2019","journal-title":"Nat Rev Gastroenterol 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