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Polydatin (PD) has been demonstrated to regulate autophagy in tumors, sepsis, and diabetes. We have recently confirmed that PD attenuated CP\u2010AKI by inhibiting ferroptosis, but it is not clear whether PD can regulate autophagy to protect from CP\u2010AKI. The purpose of this study was to investigate the effect of PD on autophagy in CP\u2010treated HK\u20102 cells and CP\u2010AKI mouse models, exploring the role of sirtuin 6 (SIRT6) upregulated by PD. In this study, the blocking of autophagy flux was observed in both CP\u2010treated HK\u20102 cells in vitro and CP\u2010AKI mouse models in vivo, whereas this blocking was reversed by PD, which was characterized by the increase of autophagy microtubule\u2010associated protein light chain 3 II expression and autophagolysosome\/autophagosome ratio and the decrease of p62 expression. Furthermore, PD also significantly increased the expression of SIRT6 in vivo and in vitro. The protective effect of PD manifested by the stimulating of autophagy flux, with the reducing of inflammatory response and oxidative stress, which included downregulation of tumor necrosis factor\u2010<jats:italic>\u03b1<\/jats:italic> and interleukin\u20101<jats:italic>\u03b2<\/jats:italic>, decreased activity of myeloperoxidase and content of malondialdehyde, and increased activity of superoxide dismutase and level of glutathione, both in vivo and in vitro, was reversed by either inhibition of autophagy flux by chloroquine or downregulation of SIRT6 by OSS\u2010128167. Taken together, the present findings provide the first evidence demonstrating that PD exhibited nephroprotective effects on CP\u2010AKI by restoring SIRT6\u2010mediated autophagy flux mechanisms.<\/jats:p>","DOI":"10.1155\/2022\/9035547","type":"journal-article","created":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T23:35:14Z","timestamp":1663371314000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Polydatin Attenuates Cisplatin\u2010Induced Acute Kidney Injury via SIRT6\u2010Mediated Autophagy Activation"],"prefix":"10.1155","volume":"2022","author":[{"given":"Zhen","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0270-4912","authenticated-orcid":false,"given":"Lu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwei","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huirong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangnan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1283-4956","authenticated-orcid":false,"given":"Hongbao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13225618"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2020101455"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom12030463"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/9947191"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-03508-y"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-020-02283-2"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2019.103688"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00854"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2016.07.032"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/1737185"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/362158"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0000000000000977"},{"key":"e_1_2_11_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/ph14090902"},{"key":"e_1_2_11_14_2","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/3337013"},{"key":"e_1_2_11_15_2","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/9218738"},{"key":"e_1_2_11_16_2","first-page":"405","article-title":"Polydatin administration improves serum biochemical parameters and oxidative stress markers during chronic alcoholism: a pilot study","volume":"29","author":"Pace M. 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