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Autophagy has been reported to be involved in arsenite (iAs<jats:sup>3+<\/jats:sup>) cytotoxicity and plays a dual role in cell proliferation and cell death. However, the effect and molecular regulative mechanisms of iAs<jats:sup>3+<\/jats:sup> on autophagy in hepatocytes remains largely unknown. Here, we found that iAs<jats:sup>3+<\/jats:sup> exposure lead to hepatotoxicity by inducing autophagosome and autolysosome accumulation. On the one hand, iAs<jats:sup>3+<\/jats:sup> promoted autophagosome synthesis by inhibiting E2F1\/mTOR pathway in L\u201002 human hepatocytes. On the other, iAs<jats:sup>3+<\/jats:sup> blocked autophagosome degradation partially via suppressing the expression of INPP5E and Rab7 as well as impairing lysosomal activity. More importantly, autophagosome and autolysosome accumulation induced by iAs<jats:sup>3+<\/jats:sup> increased the protein level of E2F7a, which could further inhibit cell viability and induce apoptosis of L\u201002 cells. The treatment of <jats:italic>Ginkgo biloba<\/jats:italic> extract (GBE) effectively reduced autophagosome and autolysosome accumulation and thus alleviated iAs<jats:sup>3+<\/jats:sup>\u2010induced hepatotoxicity. Moreover, GBE could also protect lysosomal activity, promote the phosphorylation level of E2F1 (Ser364 and Thr433) and Rb (Ser780) as well as suppress the protein level of E2F7a in iAs<jats:sup>3+<\/jats:sup>\u2010treated L\u201002 cells. Taken together, our data suggested that autophagosome and autophagolysosome accumulation play\u00a0a critical role for iAs<jats:sup>3+<\/jats:sup>\u2010induced hepatotoxicity, and GBE is a promising candidate for intervening iAs<jats:sup>3+<\/jats:sup> induced liver damage by regulating E2F1\u2010autophagy\u2010E2F7a pathway and restoring lysosomal activity.<\/jats:p>","DOI":"10.1002\/jcp.30147","type":"journal-article","created":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T03:30:33Z","timestamp":1605065433000},"page":"4050-4065","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["GBE attenuates arsenite\u2010induced hepatotoxicity by regulating E2F1\u2010autophagy\u2010E2F7a pathway and restoring lysosomal activity"],"prefix":"10.1002","volume":"236","author":[{"given":"Xiong","family":"Chen","sequence":"first","affiliation":[{"name":"The Key Laboratory of Environmental Pollution Monitoring and Disease 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