{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T18:49:21Z","timestamp":1761677361369,"version":"build-2065373602"},"reference-count":61,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T00:00:00Z","timestamp":1738886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Metabolic Technologies Inc.","award":["R43 AA023715"],"award-info":[{"award-number":["R43 AA023715"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Products of lipid peroxidation include a number of reactive lipid aldehydes including reactive dicarbonyl electrophiles (DEs) and contribute to disease processes. DEs play a significant role in the development and progression of metabolic-associated steatotic liver disease (MASLD) by contributing to oxidative stress, inflammation, protein dysfunction, and mitochondrial impairment. Reducing DE stress may be a potential strategy for managing MASLD. We hypothesized that the DE scavenger 2-hydroxybenzylamine (2-HOBA) would reduce liver injury by reducing liver protein adduct formation by DE in mouse models of MASLD. Methods: Protein adducts were measured in human livers by immunohistochemistry and immunoblot. The effects of 2-HOBA were assessed in two different mouse models of MASLD. Results: Isolevuglandin (IsoLG) protein adducts were increased in MASH-staged human livers relative to histologically normal controls. Diet-Induced Animal Model of Nonalcoholic Fatty Liver Disease (DIAMOND) mice treated with 2-HOBA exhibited significantly lower fibrosis scores (* p = 0.012) and reduced liver transaminases (AST, p = 0.03) and ALT, p = 0.012) by over 40%. In STAM (Stelic Animal Model) mice, 2-HOBA improved NAFLD activity scores (p = 0.03, NAS), hyperglycemia, and inflammatory cytokines and reduced serum F2-isoprostanes (IsoPs) by 30%, p = 0.05. These improvements were absent mRNA changes in hepatic antioxidant enzymes (Cat, Gpx1, or Sod2) or ROS-generating proteins (p22PHOX, p47PHOX, NOX4 or COX1). Conclusions: DE scavenging with 2-HOBA may be a promising therapeutic strategy for managing MASLD. While findings are currently limited to male mice, a nutraceutical that reduces liver fibrosis could significantly improve the management of MASH by offering a non-invasive treatment option to potentially slow or reverse liver scarring, delay progression to cirrhosis, and improve patient outcomes, while also providing a potential treatment option for patients who may not be suitable for other interventions like liver transplantation.<\/jats:p>","DOI":"10.3390\/nu17040610","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T11:03:51Z","timestamp":1738926231000},"page":"610","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Reactive Dicarbonyl Scavenging with 2-Hydroxybenzylamine Improves MASH"],"prefix":"10.3390","volume":"17","author":[{"given":"Joyce","family":"Cheung-Flynn","sequence":"first","affiliation":[{"name":"Department of Vascular Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8210-4289","authenticated-orcid":false,"given":"John A.","family":"Rathmacher","sequence":"additional","affiliation":[{"name":"MTI Biotech Inc., Iowa State University Research Park, Ames, IA 50010, USA"},{"name":"Department of Animal Science, Iowa State University, Ames, IA 50011, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa M.","family":"Pitchford","sequence":"additional","affiliation":[{"name":"MTI Biotech Inc., Iowa State University Research Park, Ames, IA 50010, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanhua","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3749-0598","authenticated-orcid":false,"given":"Charles Robert","family":"Flynn","sequence":"additional","affiliation":[{"name":"Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.2337\/dsi23-0010","article-title":"Understanding the Burden of Nonalcoholic Fatty Liver Disease: Time for Action","volume":"37","author":"Younossi","year":"2024","journal-title":"Diabetes Spectr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.cgh.2018.05.057","article-title":"Nonalcoholic Steatohepatitis Is the Fastest Growing Cause of Hepatocellular Carcinoma in Liver Transplant Candidates","volume":"17","author":"Younossi","year":"2019","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1016\/j.cell.2021.04.015","article-title":"Mechanisms and disease consequences of nonalcoholic fatty liver disease","volume":"184","author":"Loomba","year":"2021","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/s41591-018-0104-9","article-title":"Mechanisms of NAFLD development and therapeutic strategies","volume":"24","author":"Friedman","year":"2018","journal-title":"Nat. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1056\/NEJMoa2309000","article-title":"A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis","volume":"390","author":"Harrison","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"60","DOI":"10.17925\/EE.2023.19.1.60","article-title":"Resmetirom: An Orally Administered, Smallmolecule, Liver-directed, beta-selective THR Agonist for the Treatment of Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis","volume":"19","author":"Karim","year":"2023","journal-title":"touchREVIEWS Endocrinol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1136\/gut.2004.057968","article-title":"Immune response towards lipid peroxidation products as a predictor of progression of non-alcoholic fatty liver disease to advanced fibrosis","volume":"54","author":"Albano","year":"2005","journal-title":"Gut"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1111\/j.1572-0241.2005.41500.x","article-title":"Systemic markers of lipid peroxidation and antioxidants in patients with nonalcoholic Fatty liver disease","volume":"100","author":"Yesilova","year":"2005","journal-title":"Am. J. Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1096\/fasebj.13.10.1157","article-title":"New developments in the isoprostane pathway: Identification of novel highly reactive gamma-ketoaldehydes (isolevuglandins) and characterization of their protein adducts","volume":"13","author":"Roberts","year":"1999","journal-title":"FASEB J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6049","DOI":"10.1021\/ja00332a049","article-title":"Solvent-induced fragmentation of prostaglandin endoperoxies. New aldehydeproducts from PGH2 and a novel intramolecular 1,2-hydride shift during endoperoxide fragmentation in aqueous solution","volume":"106","author":"Salomon","year":"1984","journal-title":"J. Am. Chem. Soc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.bbalip.2009.02.003","article-title":"Low concentrations of reactive gamma-ketoaldehydes prime thromboxane-dependent human platelet aggregation via p38-MAPK activation","volume":"1791","author":"Alam","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1194\/jlr.M001040","article-title":"Isoketals form cytotoxic phosphatidylethanolamine adducts in cells","volume":"51","author":"Sullivan","year":"2010","journal-title":"J. Lipid Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1021\/bi401673b","article-title":"Levuglandin forms adducts with histone h4 in a cyclooxygenase-2-dependent manner, altering its interaction with DNA","volume":"53","author":"Carrier","year":"2014","journal-title":"Biochemistry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1046\/j.1365-2796.2000.00656.x","article-title":"Immune responses to oxidative neoepitopes on LDL and phospholipids modulate the development of atherosclerosis","volume":"247","author":"Palinski","year":"2000","journal-title":"J. Intern. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.orcp.2020.06.002","article-title":"Pro-inflammatory HDL in women with obesity and nonalcoholic steatohepatitis","volume":"14","author":"Sarkar","year":"2020","journal-title":"Obes. Res. Clin. Pract."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.freeradbiomed.2016.11.036","article-title":"Reactive gamma-ketoaldehydes as novel activators of hepatic stellate cells in vitro","volume":"102","author":"Longato","year":"2017","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1002\/hep.25778","article-title":"Pentoxifylline decreases oxidized lipid products in nonalcoholic steatohepatitis: New evidence on the potential therapeutic mechanism","volume":"56","author":"Zein","year":"2012","journal-title":"Hepatology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1369\/0022155420946402","article-title":"4-HNE Immunohistochemistry and Image Analysis for Detection of Lipid Peroxidation in Human Liver Samples Using Vitamin E Treatment in NAFLD as a Proof of Concept","volume":"68","author":"Podszun","year":"2020","journal-title":"J. Histochem. Cytochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1080\/10715762.2019.1635691","article-title":"Oxidative stress biomarkers in the serum and plasma of patients with non-alcoholic fatty liver disease (NAFLD). Can plasma AGE be a marker of NAFLD? Oxidative stress biomarkers in NAFLD patients","volume":"53","author":"Swiderska","year":"2019","journal-title":"Free Radic. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/S2468-1253(20)30077-7","article-title":"Global prevalence, incidence, and outcomes of non-obese or lean non-alcoholic fatty liver disease: A systematic review and meta-analysis","volume":"5","author":"Ye","year":"2020","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/0090-6980(89)90096-8","article-title":"Levuglandin E2 crosslinks proteins","volume":"37","author":"Iyer","year":"1989","journal-title":"Prostaglandins"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.yrtph.2018.10.017","article-title":"Subchronic (90-day) repeated dose oral toxicity study of 2-hydroxybenzylamine acetate in rabbit","volume":"100","author":"Fuller","year":"2018","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.yrtph.2018.09.025","article-title":"Subchronic (90-day) repeated dose toxicity study of 2-hydroxybenzylamine acetate in rats","volume":"99","author":"Fuller","year":"2018","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.fct.2018.09.047","article-title":"In vitro safety pharmacology evaluation of 2-hydroxybenzylamine acetate","volume":"121","author":"Fuller","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4084","DOI":"10.1038\/s41467-020-17915-w","article-title":"Scavenging of reactive dicarbonyls with 2-hydroxybenzylamine reduces atherosclerosis in hypercholesterolemic Ldlr(-\/-) mice","volume":"11","author":"Tao","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"A166","DOI":"10.1161\/hyp.60.suppl_1.A166","article-title":"Activation of T cells by dendritic cells in hypertension: A potential role of isoketal-modified proteins","volume":"60","author":"Kirabo","year":"2012","journal-title":"Hypertension"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.jacbts.2020.04.004","article-title":"Highly Reactive Isolevuglandins Promote Atrial Fibrillation Caused by Hypertension","volume":"5","author":"Prinsen","year":"2020","journal-title":"JACC Basic. Transl. Sci."},{"key":"ref_28","first-page":"A15543","article-title":"A common mechanism of autoinflammation in systemic lupus erythematosus and essential hypertension","volume":"140","author":"Patrick","year":"2019","journal-title":"Circulation"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1086\/690236","article-title":"Dysfunctional BMPR2 signaling drives an abnormal endothelial requirement for glutamine in pulmonary arterial hypertension","volume":"7","author":"Egnatchik","year":"2017","journal-title":"Pulm. Circ."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Gobert, A.P., Asim, M., Smith, T.M., Williams, K.J., Barry, D.P., Allaman, M.M., McNamara, K.M., Hawkins, C.V., Delgado, A.G., and Blanca Piazuelo, M. (2022). The nutraceutical electrophile scavenger 2-hydroxybenzylamine (2-HOBA) attenuates gastric cancer development caused by Helicobacter pylori. Biomed. Pharmacother., 158.","DOI":"10.1016\/j.biopha.2022.114092"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3233\/JAD-2011-102118","article-title":"Treatment with a gamma-ketoaldehyde scavenger prevents working memory deficits in hApoE4 mice","volume":"27","author":"Davies","year":"2011","journal-title":"J. Alzheimers. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1172\/JCI80761","article-title":"Immune activation caused by vascular oxidation promotes fibrosis and hypertension","volume":"126","author":"Wu","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Design and validation of a histological scoring system for nonalcoholic fatty liver disease","volume":"41","author":"Kleiner","year":"2005","journal-title":"Hepatology"},{"key":"ref_34","unstructured":"National Research Council (2010). Guide for the Care and Use of Laboratory Animals, National Academies Press."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.4254\/wjh.v7.i24.2551","article-title":"Role of pentoxifylline in non-alcoholic fatty liver disease in high-fat diet-induced obesity in mice","volume":"7","author":"Acedo","year":"2015","journal-title":"World J. Hepatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s00795-013-0016-1","article-title":"A murine model for non-alcoholic steatohepatitis showing evidence of association between diabetes and hepatocellular carcinoma","volume":"46","author":"Fujii","year":"2013","journal-title":"Med. Mol. Morphol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"9383","DOI":"10.1073\/pnas.87.23.9383","article-title":"A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism","volume":"87","author":"Morrow","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1096\/fj.01-0696fje","article-title":"Effects of reactive gamma-ketoaldehydes formed by the isoprostane pathway (isoketals) and cyclooxygenase pathway (levuglandins) on proteasome function","volume":"16","author":"Davies","year":"2002","journal-title":"Faseb J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1016\/j.freeradbiomed.2004.02.014","article-title":"Localization of isoketal adducts in vivo using a single-chain antibody","volume":"36","author":"Davies","year":"2004","journal-title":"Free Radic. Biol. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1530\/JOE-15-0409","article-title":"Metformin improves hepatic IRS2\/PI3K\/Akt signaling in insulin-resistant rats of NASH and cirrhosis","volume":"229","author":"Xu","year":"2016","journal-title":"J. Endocrinol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1053\/j.gastro.2016.02.066","article-title":"Pathogenesis of Nonalcoholic Steatohepatitis","volume":"150","author":"Machado","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"11960","DOI":"10.1073\/pnas.220413597","article-title":"Phosphorylation and inactivation of glycogen synthase kinase 3 by protein kinase A","volume":"97","author":"Fang","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"39450","DOI":"10.1074\/jbc.M111.265330","article-title":"Mechanical regulation of glycogen synthase kinase 3beta (GSK3beta) in mesenchymal stem cells is dependent on Akt protein serine 473 phosphorylation via mTORC2 protein","volume":"286","author":"Case","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.pharmthera.2014.11.016","article-title":"Glycogen synthase kinase-3 (GSK3): Regulation, actions, and diseases","volume":"148","author":"Beurel","year":"2015","journal-title":"Pharmacol. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/hep.510250216","article-title":"Effect of chronic ethanol feeding on lipid peroxidation and protein oxidation in relation to liver pathology","volume":"25","author":"Rouach","year":"1997","journal-title":"Hepatology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"13447","DOI":"10.1074\/jbc.M313349200","article-title":"Modification of proteins by isoketal-containing oxidized phospholipids","volume":"279","author":"Brame","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1016\/j.freeradbiomed.2009.07.015","article-title":"Formation of gamma-ketoaldehyde-protein adducts during ethanol-induced liver injury in mice","volume":"47","author":"Roychowdhury","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.redox.2014.12.009","article-title":"Steatosis-induced proteins adducts with lipid peroxidation products and nuclear electrophilic stress in hepatocytes","volume":"4","author":"Anavi","year":"2015","journal-title":"Redox Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1001\/jama.2024.1215","article-title":"Aspirin for Metabolic Dysfunction-Associated Steatotic Liver Disease Without Cirrhosis: A Randomized Clinical Trial","volume":"331","author":"Simon","year":"2024","journal-title":"JAMA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1007\/s11745-001-0812-7","article-title":"Polyunsaturated fatty acids, inflammation, and immunity","volume":"36","author":"Calder","year":"2001","journal-title":"Lipids"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0925-4439(99)00025-3","article-title":"The mechanism of inhibition of beta-oxidation by aspirin metabolites in skin fibroblasts from Reye\u2019s syndrome patients and controls","volume":"1454","author":"Glasgow","year":"1999","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1126\/science.1215327","article-title":"The ancient drug salicylate directly activates AMP-activated protein kinase","volume":"336","author":"Hawley","year":"2012","journal-title":"Science"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"E1099","DOI":"10.1152\/ajpendo.00185.2011","article-title":"Aspirin reduces hypertriglyceridemia by lowering VLDL-triglyceride production in mice fed a high-fat diet","volume":"301","author":"Vroegrijk","year":"2011","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.jacl.2023.06.005","article-title":"Clinical trials to improve outcomes in patients with elevated Lp(a) undergoing PCI: The time has arrived","volume":"17","author":"Tsimikas","year":"2023","journal-title":"J. Clin. Lipidol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Khan, P., Bhattacharya, A., Sengupta, D., Banerjee, S., Adhikary, A., and Das, T. (2019). Aspirin enhances cisplatin sensitivity of resistant non-small cell lung carcinoma stem-like cells by targeting mTOR-Akt axis to repress migration. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-53134-0"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1158\/0008-5472.CAN-16-2400","article-title":"Aspirin Suppresses Growth in PI3K-Mutant Breast Cancer by Activating AMPK and Inhibiting mTORC1 Signaling","volume":"77","author":"Henry","year":"2017","journal-title":"Cancer Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1007\/s10753-023-01801-w","article-title":"Inflammation Biomarker Response to Oral 2-Hydroxybenzylamine (2-HOBA) Acetate in Healthy Humans","volume":"46","author":"Rathmacher","year":"2023","journal-title":"Inflammation"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1097\/MEG.0000000000002741","article-title":"Prevalence, trends, and characteristics of metabolic dysfunction-associated steatotic liver disease among the US population aged 12-79 years","volume":"36","author":"Shen","year":"2024","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Pitchford, L.M., Driver, P.M., Fuller, J.C., Akers, W.S., Abumrad, N.N., Amarnath, V., Milne, G.L., Chen, S.C., Ye, F., and Roberts, L.J. (2020). Safety, tolerability, and pharmacokinetics of repeated oral doses of 2-hydroxybenzylamine acetate in healthy volunteers: A double-blind, randomized, placebo-controlled clinical trial. BMC Pharmacol. Toxicol., 21.","DOI":"10.1186\/s40360-020-0382-y"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Pitchford, L.M., Rathmacher, J.A., Fuller, J.C., Daniels, J.S., Morrison, R.D., Akers, W.S., Abumrad, N.N., Amarnath, V., Currey, P.M., and Roberts, L.J. (2019). First-in-human study assessing safety, tolerability, and pharmacokinetics of 2-hydroxybenzylamine acetate, a selective dicarbonyl electrophile scavenger, in healthy volunteers. BMC Pharmacol. Toxicol., 20.","DOI":"10.1186\/s40360-018-0281-7"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.jhep.2024.04.034","article-title":"FGF21 agonists: An emerging therapeutic for metabolic dysfunction-associated steatohepatitis and beyond","volume":"81","author":"Harrison","year":"2024","journal-title":"J. Hepatol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/4\/610\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:29:01Z","timestamp":1760027341000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/4\/610"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,7]]},"references-count":61,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["nu17040610"],"URL":"https:\/\/doi.org\/10.3390\/nu17040610","relation":{},"ISSN":["2072-6643"],"issn-type":[{"type":"electronic","value":"2072-6643"}],"subject":[],"published":{"date-parts":[[2025,2,7]]}}}