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Trehalose (Tr), a multifunctional bioactive disaccharide, possesses potential kidney protective properties. Nevertheless, the specific biological function of Tr in antagonizing kidney injury induced by Cd remains to be elucidated. Herein, an in vivo model of Tr antagonizing Cd nephrotoxicity was established and the indictors related to kidney function, oxidative stress, and apoptosis were detected to investigate the molecular mechanism underlying the Tr-protection against Cd-induced kidney injury of rats. Firstly, Tr significantly declined the levels of blood urea nitrogen (BUN) and serum creatinine, and partially restored renal pathological changes caused by Cd. Secondly, Cd exposure significantly increased the malondialdehyde (MDA) content, and decreased the levels of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and glutathione (GSH) in serum. However, Tr significantly ameliorated these abnormal alterations. Moreover, Tr regulated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway to suppress the Cd-induced nuclear translocation of Nrf2 and the up-regulation of heme oxygenase-1 (HO-1) and NAD (P) H quinone reductase-1 (NQO1). Meanwhile, Tr significantly reversed the increased Sequestosome-1(SQSTM1\/p62) and decreased Kelch-like ECH associated protein-1 (Keap1) protein levels induced by Cd. Thirdly, further mechanistic exploration suggested that Tr inhibited the mitochondrial apoptotic signaling pathway induced by Cd. Collectively, the results indicated that Tr exerts antioxidant and anti-apoptosis functions involving the Nrf2 and mitochondrial apoptotic signaling pathways to protect against Cd-induced kidney injury in rats.<\/jats:p>","DOI":"10.1039\/d0mt00213e","type":"journal-article","created":{"date-parts":[[2020,11,3]],"date-time":"2020-11-03T01:03:30Z","timestamp":1604365410000},"page":"2098-2107","update-policy":"https:\/\/doi.org\/10.1039\/rsc_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Involvement of Nrf2 and mitochondrial apoptotic signaling in trehalose protection against cadmium-induced kidney injury"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5487-6065","authenticated-orcid":false,"given":"Rui-Feng","family":"Fan","sequence":"first","affiliation":[{"name":"College of Animal Science and Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Tai\u2019an City, Shandong Province, 271018, China. Fax: +86 538-8241419; Tel: +86-538-8242478"},{"name":"Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, 61 Daizong Street, Tai\u2019an City, Shandong Province, 271018, China"},{"name":"Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, 61 Daizong Street, Tai\u2019an City, Shandong Province, 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Fa","family":"Li","sequence":"additional","affiliation":[{"name":"Experimental Center, Shandong University of Traditional Chinese Medicine, Ji\u2019nan City, Shandong Province, 250355, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shandong Provincial Center for Animal Disease Control and Prevention, Ji\u2019nan City, Shandong Province, 250022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8020-8674","authenticated-orcid":false,"given":"Zhen-Yong","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Tai\u2019an City, Shandong Province, 271018, China. Fax: +86 538-8241419; Tel: +86-538-8242478"},{"name":"Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, 61 Daizong Street, Tai\u2019an City, Shandong Province, 271018, China"},{"name":"Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, 61 Daizong Street, Tai\u2019an City, Shandong Province, 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,11,23]]},"reference":[{"key":"2021121004363522300_cit1","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.taap.2009.04.020","article-title":"Current status of cadmium as an environmental health problem","volume":"238","author":"J\u00e4rup","year":"2009","journal-title":"Toxicol. Appl. 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