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Studies have demonstrated that nano\u2010TiO<jats:sub>2<\/jats:sub> could induce hepatotoxicity through oxidative stress, and lycopene has strong antioxidant capacity. The present study aimed to explore if lycopene protects the liver of mice from nano\u2010TiO<jats:sub>2<\/jats:sub> damage. Ninety\u2010six ICR mice were randomly divided into eight groups. They were control group, nano\u2010TiO<jats:sub>2<\/jats:sub>\u2010treated group (50\u2009mg\/kg BW), lycopene\u2010treated groups (5, 20, and 40\u2009mg\/kg BW), and 50\u2009mg\/kg BW nano\u2010TiO<jats:sub>2<\/jats:sub>\u2010 and lycopene\u2010co\u2010treated groups (nano\u2010TiO<jats:sub>2<\/jats:sub>\u2009+\u20095 mg\/kg BW of lycopene, nano\u2010TiO<jats:sub>2<\/jats:sub>\u2009+\u200920\u2009mg\/kg BW of lycopene, nano\u2010TiO<jats:sub>2<\/jats:sub>\u2009+\u200940\u2009mg\/kg BW of lycopene). After treated by gavage for 30\u2009days, the histopathology of the liver was observed. Liver function was evaluated using changes in serum biochemical indicators of the liver (AST, ALT, ALP); and the level of ROS was indirectly reflected by the level of SOD, GSH\u2010Px, MDA, GSH, and T\u2010AOC. TUNEL assay was performed to examine the apoptosis of hepatocytes. Proteins of p53, cleaved\u2010caspase 9, cleaved\u2010caspase 3, Bcl\u20102, and Bax as well as p38 were detected. Results showed that lycopene alleviated the liver pathological damage and reduced the injury to liver function induced by nano\u2010TiO<jats:sub>2<\/jats:sub>, as well as decreased nano\u2010TiO<jats:sub>2<\/jats:sub>\u2010induced ROS. Meanwhile, lycopene mitigated apoptosis resulting from nano\u2010TiO<jats:sub>2<\/jats:sub>, accompanied by the reversed expression of apoptosis\u2010related proteins. Furthermore, lycopene significantly reversed the upregulation of p\u2010p38 induced by nano\u2010TiO<jats:sub>2<\/jats:sub>. In conclusion, this study demonstrated that nano\u2010TiO<jats:sub>2<\/jats:sub> resulted in hepatocyte apoptosis through ROS\/ROS\u2010p38 MAPK pathway and led to liver function injury. Lycopene protected mice liver against the hepatotoxicity of nano\u2010TiO<jats:sub>2<\/jats:sub> through antioxidant property.<\/jats:p>","DOI":"10.1002\/jat.4433","type":"journal-article","created":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T02:24:58Z","timestamp":1673490298000},"page":"913-928","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Protective effects of lycopene on TiO<sub>2<\/sub> nanoparticle\u2010induced damage in the liver of mice"],"prefix":"10.1002","volume":"43","author":[{"given":"Hongmei","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Preventive Medicine\/the Key Laboratories for Xinjiang Endemic and Ethnic Diseases, School of Medicine Shihezi University  Shihezi 832003 Xinjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine\/the Key Laboratories for Xinjiang Endemic and Ethnic Diseases, School of Medicine Shihezi University  Shihezi 832003 Xinjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxin","family":"Deng","sequence":"additional","affiliation":[{"name":"Shiyan centers for disease control and prevention  Shiyan 442000 Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3038-7499","authenticated-orcid":false,"given":"Guanling","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine\/the Key Laboratories for Xinjiang Endemic and Ethnic Diseases, School of Medicine Shihezi University  Shihezi 832003 Xinjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine Shihezi University  Shihezi 832002 Xinjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,2,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S192382"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2147\/ijn.S47174"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111831"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/1354750x.2019.1620336"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3109\/17435390.2014.940404"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6632128"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1515\/aiht-2016-67-2762"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2011.09.044"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12989-021-00422-1"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-007-0082-8"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/17435390.2020.1778809"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0304-3835(00)00401-8"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemosphere.2020.128346"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/nano10112102"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jenvman.2020.111428"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.12.151"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.201201506"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1039\/d0nr05591c"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12989-019-0332-2"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3769"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-008-0284-8"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2009.12.022"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S176087"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-25852-4"},{"key":"e_1_2_9_26_1","unstructured":"European Commission. 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