{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T11:19:23Z","timestamp":1787915963212,"version":"build-2784847793"},"reference-count":45,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,12,19]],"date-time":"2021-12-19T00:00:00Z","timestamp":1639872000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2017YFC1600200"],"award-info":[{"award-number":["2017YFC1600200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2017YFC1600500"],"award-info":[{"award-number":["2017YFC1600500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Heavy metals exposure has been associated with liver dysfunction in recent reports, while the hepatoxicity of lead (Pb) and cadmium (Cd) has been well established. However, the combined effects of multi\u2010metal in real\u2010world scenario on liver dysfunction are still unclear. This cross\u2010sectional study examined associations between 10 biomarkers of early liver injury and multiple heavy metals levels. The levels of heavy metals\/metalloid (magnesium [Mg], calcium [Ca], iron [Fe], zinc [Zn], arsenic [As], Cd, copper [Cu], and Pb) were measured in blood and urinary sample collected from 725 participants in a Cd\u2010polluted area and an unpolluted area in southwest China. The early liver dysfunction biomarkers included the liver enzymes (ALT, ALP, AST, and GGT), proteins (TP, ALB, and GLO), and bilirubin (TBIL, DBIL, and IBIL). Confounder\u2010adjusted beta coefficients were determined using multiple linear regression model analysis for the group\u2010classified and gender\u2010classified samples. Our results showed that blood Fe, Cd, and Cu levels were found to be positively related to elevated ALT levels and blood Cu was positively associated with AST levels in the Cd\u2010polluted area, while the highest blood Zn quartile in the polluted area and blood Mg quartile in the unpolluted area were associated with lower ALT levels. Our finding implies that industrial pollution results in heavy metals of Cd and Pb exposure and effects of Fe, Cd, Cu, and Pb in the Cd\u2010polluted area may be the main contributors to increase the risk of liver dysfunction while Zn in the Cd\u2010polluted area and Mg in the unpolluted area may be the protective factors.<\/jats:p>","DOI":"10.1002\/jat.4276","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T00:39:20Z","timestamp":1639960760000},"page":"1044-1056","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Heavy metals exposure is associated with early liver dysfunction among rural residents aged 40\u201375\u2009years in southwest China"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8885-8906","authenticated-orcid":false,"given":"Zhirui","family":"Yang","sequence":"first","affiliation":[{"name":"West China School of Public Health\/West China Fourth Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomeng","family":"Li","sequence":"additional","affiliation":[{"name":"West China School of Public Health\/West China Fourth Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Tian","sequence":"additional","affiliation":[{"name":"West China School of Public Health\/West China Fourth Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Safety Sichuan Center for Disease Control and Prevention  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Safety Sichuan Center for Disease Control and Prevention  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0519-4935","authenticated-orcid":false,"given":"Jinyao","family":"Chen","sequence":"additional","affiliation":[{"name":"West China School of Public Health\/West China Fourth Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lishi","family":"Zhang","sequence":"additional","affiliation":[{"name":"West China School of Public Health\/West China Fourth Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,19]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"1034","article-title":"Oxidative stress, biochemical alterations, and hyperlipidemia in female rats induced by lead chronic toxicity during puberty and post puberty periods","volume":"18","author":"Alya A.","year":"2015","journal-title":"Iranian Journal of Basic Medical Sciences"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0069972"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.20530"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2017.03.014"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.1002720"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2015.12.042"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-27411-3"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2005.05.025"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0406085102"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/46.12.2027"},{"key":"e_1_2_9_12_1","first-page":"10","article-title":"Cadmium levels and sources of exposure among Canadian adults","volume":"27","author":"Garner R.","year":"2016","journal-title":"Health Reports"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2017.01.040"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2019.113683"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfv149"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.36061"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2018.01.002"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2004.04.006"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0201454"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11605-013-2210-9"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-069x-10-64"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10534-010-9328-y"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/oemed-2012-101063"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/142856"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2016.517"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3908"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.Epi-07-2816"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2012.11.027"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2016-014215"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2013.07.013"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0300-483x(01)00345-6"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/10.1016\/s0946-672x(03)80026-3"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCO.0b013e3283312956"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1684\/mrh.2010.0204"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2011.05.008"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2016.31.1.25"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173513"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40572-016-0120-1"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1177\/0192623312468517"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3968"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mpaic.2021.05.010"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2020.111242"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-18076-5"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22363"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12940-017-0304-7"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemosphere.2021.132190"}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.4276","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jat.4276","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.4276","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T13:17:11Z","timestamp":1760534231000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.4276"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,19]]},"references-count":45,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,6]]}},"alternative-id":["10.1002\/jat.4276"],"URL":"https:\/\/doi.org\/10.1002\/jat.4276","archive":["Portico"],"relation":{},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"value":"0260-437X","type":"print"},{"value":"1099-1263","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,19]]},"assertion":[{"value":"2021-08-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}