{"id":"https://openalex.org/W7224274376","doi":"https://doi.org/10.1093/toxsci/kfag144","title":"Loss of LKB1 protects against acetaminophen hepatotoxicity in mice through sex-specific mechanisms","display_name":"Loss of LKB1 protects against acetaminophen hepatotoxicity in mice through sex-specific mechanisms","publication_year":2026,"publication_date":"2026-10-29","ids":{"openalex":"https://openalex.org/W7224274376","doi":"https://doi.org/10.1093/toxsci/kfag144","pmid":"https://pubmed.ncbi.nlm.nih.gov/42954343"},"language":"en","primary_location":{"id":"doi:10.1093/toxsci/kfag144","doi":"https://doi.org/10.1093/toxsci/kfag144","is_oa":true,"landing_page_url":"https://doi.org/10.1093/toxsci/kfag144","pdf_url":"https://academic.oup.com/toxsci/advance-article-pdf/doi/10.1093/toxsci/kfag144/72584686/kfag144.pdf","source":{"id":"https://openalex.org/S186282544","display_name":"Toxicological Sciences","issn_l":"1096-0929","issn":["1096-0929","1096-6080"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Toxicological Sciences","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"hybrid","oa_url":"https://academic.oup.com/toxsci/advance-article-pdf/doi/10.1093/toxsci/kfag144/72584686/kfag144.pdf","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5144417188","display_name":"Debasree Bhadra","orcid":"https://orcid.org/0009-0002-5575-5374","observed_orcids":["https://orcid.org/0009-0002-5575-5374"]},"institutions":[{"id":"https://openalex.org/I79620101","display_name":"University of Arkansas for Medical Sciences","ror":"https://ror.org/00xcryt71","country_code":"US","type":"education","lineage":["https://openalex.org/I79620101"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Debasree Bhadra","raw_affiliation_strings":["College of Medicine, University of Arkansas for Medical Sciences Dept. of Pharmacology and Toxicology, , Little Rock, AR"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"College of Medicine, University of Arkansas for Medical Sciences Dept. of Pharmacology and Toxicology, , Little Rock, AR","institution_ids":["https://openalex.org/I79620101"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5160099226","display_name":"Jenna S Caswell","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I79620101","display_name":"University of Arkansas for Medical Sciences","ror":"https://ror.org/00xcryt71","country_code":"US","type":"education","lineage":["https://openalex.org/I79620101"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jenna S Caswell","raw_affiliation_strings":["College of Medicine, University of Arkansas for Medical Sciences Dept. of Pharmacology and Toxicology, , Little Rock, AR"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"College of Medicine, University of Arkansas for Medical Sciences Dept. of Pharmacology and Toxicology, , Little Rock, AR","institution_ids":["https://openalex.org/I79620101"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5160119414","display_name":"Kathryn L Smith","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I79620101","display_name":"University of Arkansas for Medical Sciences","ror":"https://ror.org/00xcryt71","country_code":"US","type":"education","lineage":["https://openalex.org/I79620101"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Kathryn L Smith","raw_affiliation_strings":["Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences Dept. of Environmental Health Sciences, , Little Rock, AR"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences Dept. of Environmental Health Sciences, , Little Rock, AR","institution_ids":["https://openalex.org/I79620101"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5046152669","display_name":"Natalie Porat\u2010Shliom","orcid":"https://orcid.org/0000-0003-2676-8483","observed_orcids":["https://orcid.org/0000-0003-2676-8483"]},"institutions":[{"id":"https://openalex.org/I1299303238","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238"]},{"id":"https://openalex.org/I4210140884","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238","https://openalex.org/I4210140884"]},{"id":"https://openalex.org/I4210149717","display_name":"Center for Cancer Research","ror":"https://ror.org/05bjen692","country_code":"US","type":"facility","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238","https://openalex.org/I4210140884","https://openalex.org/I4210149717"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Natalie Porat-Shliom","raw_affiliation_strings":["Cell Biology and Imaging Section, Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cell Biology and Imaging Section, Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD","institution_ids":["https://openalex.org/I1299303238","https://openalex.org/I4210140884","https://openalex.org/I4210149717"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5031360889","display_name":"Mitchell R. McGill","orcid":"https://orcid.org/0000-0002-0401-0463","observed_orcids":["https://orcid.org/0000-0002-0401-0463"]},"institutions":[{"id":"https://openalex.org/I79620101","display_name":"University of Arkansas for Medical Sciences","ror":"https://ror.org/00xcryt71","country_code":"US","type":"education","lineage":["https://openalex.org/I79620101"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Mitchell R McGill","raw_affiliation_strings":["College of Medicine, University of Arkansas for Medical Sciences Dept. of Pharmacology and Toxicology, , Little Rock, AR","Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences Dept. of Environmental Health Sciences, , Little Rock, AR","University of Arkansas for Medical Sciences Dept. of Pathology, College of Medicine, , Little Rock, AR"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"College of Medicine, University of Arkansas for Medical Sciences Dept. of Pharmacology and Toxicology, , Little Rock, AR","institution_ids":["https://openalex.org/I79620101"]},{"raw_affiliation_string":"Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences Dept. of Environmental Health Sciences, , Little Rock, AR","institution_ids":["https://openalex.org/I79620101"]},{"raw_affiliation_string":"University of Arkansas for Medical Sciences Dept. of Pathology, College of Medicine, , Little Rock, AR","institution_ids":["https://openalex.org/I79620101"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":4,"corresponding_author_ids":["https://openalex.org/A5031360889"],"corresponding_institution_ids":["https://openalex.org/I79620101"],"apc_list":{"value":4671,"currency":"USD","value_usd":4671},"apc_paid":{"value":4671,"currency":"USD","value_usd":4671},"fwci":0.0,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":{"value":0.85991803,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11465","display_name":"Drug-Induced Hepatotoxicity and Protection","score":1.0,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11465","display_name":"Drug-Induced Hepatotoxicity and Protection","score":1.0,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10966","display_name":"Liver physiology and pathology","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2721","display_name":"Hepatology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10375","display_name":"Pharmacogenetics and Drug Metabolism","score":0.0,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/liver-kinase-b1","display_name":"LKB1","score":0.8619999885559082},{"id":"https://openalex.org/keywords/acetaminophen-induced-hepatotoxicity","display_name":"acetaminophen hepatotoxicity","score":0.9919999837875366},{"id":"https://openalex.org/keywords/acute-liver-failure","display_name":"acute liver failure","score":0.972000002861023},{"id":"https://openalex.org/keywords/sex-differences","display_name":"sex differences","score":0.9179999828338623},{"id":"https://openalex.org/keywords/cyp2e1","display_name":"CYP2E1","score":0.9729999899864197},{"id":"https://openalex.org/keywords/pentose-phosphate-pathway","display_name":"pentose phosphate pathway","score":0.8889999985694885},{"id":"https://openalex.org/keywords/glucose-6-phosphate-dehydrogenase","display_name":"glucose-6-phosphate dehydrogenase","score":0.9919999837875366},{"id":"https://openalex.org/keywords/nadph","display_name":"NADPH","score":0.7860000133514404},{"id":"https://openalex.org/keywords/oxidative-stress","display_name":"oxidative stress","score":0.9729999899864197},{"id":"https://openalex.org/keywords/hepatocyte-specific-knockout-mice","display_name":"hepatocyte-specific knockout mice","score":0.824999988079071}],"concepts":[{"id":"https://openalex.org/C140027455","wikidata":"https://www.wikidata.org/wiki/Q14864434","display_name":"CYP2E1","level":4,"score":0.835099995136261},{"id":"https://openalex.org/C2778722691","wikidata":"https://www.wikidata.org/wiki/Q57055","display_name":"Acetaminophen","level":2,"score":0.8065999746322632},{"id":"https://openalex.org/C2776637226","wikidata":"https://www.wikidata.org/wiki/Q6658207","display_name":"Liver injury","level":2,"score":0.6029000282287598},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5358999967575073},{"id":"https://openalex.org/C57600042","wikidata":"https://www.wikidata.org/wiki/Q227564","display_name":"Oxidative phosphorylation","level":2,"score":0.534600019454956},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.5235000252723694},{"id":"https://openalex.org/C3409486","wikidata":"https://www.wikidata.org/wiki/Q827489","display_name":"Pentose phosphate pathway","level":4,"score":0.45660001039505005},{"id":"https://openalex.org/C88045685","wikidata":"https://www.wikidata.org/wiki/Q174576","display_name":"Activator (genetics)","level":3,"score":0.4481000006198883},{"id":"https://openalex.org/C182704531","wikidata":"https://www.wikidata.org/wiki/Q1364740","display_name":"Knockout mouse","level":3,"score":0.44690001010894775},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.444599986076355},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.4244000017642975},{"id":"https://openalex.org/C28859421","wikidata":"https://www.wikidata.org/wiki/Q39572","display_name":"Mitochondrion","level":2,"score":0.40619999170303345},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.3862000107765198},{"id":"https://openalex.org/C184235292","wikidata":"https://www.wikidata.org/wiki/Q421851","display_name":"Kinase","level":2,"score":0.35749998688697815},{"id":"https://openalex.org/C2776151105","wikidata":"https://www.wikidata.org/wiki/Q898814","display_name":"Oxidative stress","level":2,"score":0.3310000002384186},{"id":"https://openalex.org/C526171541","wikidata":"https://www.wikidata.org/wiki/Q407693","display_name":"Cytochrome P450","level":3,"score":0.32839998602867126},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.31200000643730164},{"id":"https://openalex.org/C207583985","wikidata":"https://www.wikidata.org/wiki/Q128723","display_name":"Wild type","level":4,"score":0.2782999873161316},{"id":"https://openalex.org/C48349386","wikidata":"https://www.wikidata.org/wiki/Q424361","display_name":"Reactive oxygen species","level":2,"score":0.2703999876976013},{"id":"https://openalex.org/C2780196906","wikidata":"https://www.wikidata.org/wiki/Q421793","display_name":"Glucose-6-phosphate dehydrogenase","level":4,"score":0.26820001006126404},{"id":"https://openalex.org/C190283241","wikidata":"https://www.wikidata.org/wiki/Q14599311","display_name":"Apoptosis","level":2,"score":0.2540999948978424}],"mesh":[],"locations_count":2,"locations":[{"id":"doi:10.1093/toxsci/kfag144","doi":"https://doi.org/10.1093/toxsci/kfag144","is_oa":true,"landing_page_url":"https://doi.org/10.1093/toxsci/kfag144","pdf_url":"https://academic.oup.com/toxsci/advance-article-pdf/doi/10.1093/toxsci/kfag144/72584686/kfag144.pdf","source":{"id":"https://openalex.org/S186282544","display_name":"Toxicological Sciences","issn_l":"1096-0929","issn":["1096-0929","1096-6080"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Toxicological Sciences","raw_type":"journal-article"},{"id":"pmid:42954343","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/42954343","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Toxicological sciences : an official journal of the Society of Toxicology","raw_type":"Journal Article"}],"best_oa_location":{"id":"doi:10.1093/toxsci/kfag144","doi":"https://doi.org/10.1093/toxsci/kfag144","is_oa":true,"landing_page_url":"https://doi.org/10.1093/toxsci/kfag144","pdf_url":"https://academic.oup.com/toxsci/advance-article-pdf/doi/10.1093/toxsci/kfag144/72584686/kfag144.pdf","source":{"id":"https://openalex.org/S186282544","display_name":"Toxicological Sciences","issn_l":"1096-0929","issn":["1096-0929","1096-6080"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Toxicological Sciences","raw_type":"journal-article"},"sustainable_development_goals":[{"score":0.98580002784729,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7224274376.pdf","grobid_xml":"https://content.openalex.org/works/W7224274376.grobid-xml"},"referenced_works_count":22,"referenced_works":["https://openalex.org/W1521943312","https://openalex.org/W1989446240","https://openalex.org/W2010238890","https://openalex.org/W2033174557","https://openalex.org/W2037691927","https://openalex.org/W2044874695","https://openalex.org/W2056475446","https://openalex.org/W2059655597","https://openalex.org/W2079118329","https://openalex.org/W2092165077","https://openalex.org/W2129070184","https://openalex.org/W2136789586","https://openalex.org/W2140736672","https://openalex.org/W2145560274","https://openalex.org/W2333107025","https://openalex.org/W2472507941","https://openalex.org/W2989726581","https://openalex.org/W3092934667","https://openalex.org/W4211175126","https://openalex.org/W4388215218","https://openalex.org/W4412424500","https://openalex.org/W4412556351"],"related_works":["https://openalex.org/W2057676577","https://openalex.org/W2131375972","https://openalex.org/W2015479450","https://openalex.org/W2073061104","https://openalex.org/W2729295129","https://openalex.org/W2898417872","https://openalex.org/W3137866140","https://openalex.org/W1986291780","https://openalex.org/W2897901019","https://openalex.org/W2009593507"],"abstract_inverted_index":{"Acetaminophen":[0],"(APAP)":[1],"overdose":[2],"is":[3,31,116,229,237],"a":[4,117,238],"major":[5,118],"cause":[6],"of":[7,16,76,120,196],"acute":[8],"liver":[9,17,55,243],"failure":[10],"(ALF).":[11],"We":[12,218],"previously":[13],"observed":[14],"activation":[15,203,236],"kinase":[18],"B1":[19],"(LKB1)":[20],"in":[21,33,149,157,170,191,205,216,231,242,245],"non-surviving":[22],"patients":[23],"with":[24,51,64,179],"APAP-induced":[25],"ALF.":[26],"Thus,":[27],"we":[28,40,127,140],"hypothesized":[29,128],"LKB1":[30,43,67,202,220],"detrimental":[32],"APAP":[34,52,71,186,232],"hepatotoxicity.":[35,72],"To":[36,137],"test":[37,138],"our":[38,65,197],"hypothesis,":[39,66],"overdosed":[41],"hepatocyte-specific":[42],"knockout":[44],"(KO)":[45],"mice":[46,132,160],"and":[47,53,59,100,166,187,208,223,234,247],"wildtype":[48],"(WT)":[49],"littermates":[50],"measured":[54,141],"injury":[56,244],"2,":[57],"6,":[58],"24":[60],"h":[61,177],"later.":[62],"Consistent":[63],"KO":[68,99,131,173],"protected":[69,184],"against":[70,185],"However,":[73],"the":[74,146,150,171,180,224],"mechanisms":[75],"protection":[77],"were":[78],"sex-specific.":[79],"Male":[80],"KOs":[81,105],"had":[82,107],"lower":[83,88],"NAPQI":[84,93],"formation":[85,94],"due":[86],"to":[87,122,162],"mitochondrial":[89,227],"CYP2E1.":[90],"In":[91],"contrast,":[92],"was":[95,155,214],"similar":[96],"between":[97],"female":[98,104,130,158,172,209],"WT":[101,159,164,192],"mice,":[102],"but":[103],"still":[106],"reduced":[108],"oxidative":[109,124,151],"stress.":[110],"The":[111],"pentose":[112],"phosphate":[113],"pathway":[114],"(PPP)":[115],"source":[119],"NADPH":[121,190],"counter":[123],"stress,":[125],"so":[126],"that":[129,226],"have":[133],"increased":[134,156,169,188],"PPP":[135,235],"enzymes.":[136],"that,":[139],"hepatic":[142,189],"glucose-6-phosphate":[143],"dehydrogenase":[144],"(G6PD),":[145],"rate-limiting":[147],"enzyme":[148],"PPP.":[152],"Importantly,":[153],"G6PD":[154,181],"compared":[161],"male":[163,207],"animals":[165],"even":[167],"further":[168],"mice.":[174],"Furthermore,":[175],"1.5":[176],"post-treatment":[178],"activator":[182],"AG1":[183],"animals.":[193],"Finally,":[194],"re-analysis":[195],"prior":[198],"proteomics":[199],"data":[200],"revealed":[201],"occurred":[204],"both":[206],"ALF":[210],"non-survivors,":[211],"though":[212],"it":[213],"greater":[215],"males.":[217],"conclude":[219],"regulates":[221],"CYP2E1":[222,228],"PPP,":[225],"critical":[230],"toxicity,":[233],"potential":[239],"therapeutic":[240],"approach":[241],"men":[246],"women.":[248]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2026-10-30T00:00:00"}
