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Cells were treated with aqueous extracts of Senecio (10 mg\u00b7mL<jats:sup>\u20131<\/jats:sup>) with and without NAC. Cytotoxicity was determined by using the MTT assay. Total glutathione (GSH) was measured by using the Tietze assay. Cells were also treated with aqueous extracts of Senecio in the presence or absence of 50 \u03bcmol\/L caspase-3 inhibitor (IDN) for 24 h. Apoptosis was determined by transmission electron microscopy, and DNA fragmentation was determined by ELISA and terminal dUTP nick-end labelling (TUNEL). Senecio produced cytotoxicity and depleted GSH in a concentration- and time-dependent manner. A significant depletion in GSH was observed after 15 min (p &lt; 0.001 vs. control), whereas significant cytotoxicity was only observed after 3 h (p &lt; 0.001 vs. control). Treatment with NAC prevented Senecio-induced GSH depletion and resulted in a significant decrease in Senecio-induced cytotoxicity (p &lt; 0.001 vs. NAC-untreated cells). Treatment with Senecio for 24 h resulted in 22% \u00b1 2.5% (p\u00a0&lt;\u00a00.001) apoptosis (vs. control). Pretreatment with 50 \u03bcmol caspase inhibitor reduced Senecio-induced apoptosis significantly (vs. non-exposed to IDN) (12% \u00b1 1.5%; p\u00a0&lt;\u00a00.05). Our results suggest the mechanism of Senecio-induced cytotoxicity in HepG2 cells in vitro involves depletion of cellular GSH. Cytotoxicity is reduced by supplementation with NAC, which thus prevents GSH depletion. Caspase activation is involved in Senecio-induced apoptosis.<\/jats:p>","DOI":"10.1139\/y07-107","type":"journal-article","created":{"date-parts":[[2007,12,7]],"date-time":"2007-12-07T16:17:15Z","timestamp":1197044235000},"page":"1063-1075","source":"Crossref","is-referenced-by-count":16,"title":["Senecio latifolius induces in vitro hepatocytotoxicity in a human cell lineThis article is one of a selection of papers published in this special issue (part 2 of 2) on the Safety and Efficacy of Natural Health Products."],"prefix":"10.1139","volume":"85","author":[{"given":"Manuela G.","family":"Neuman","sequence":"first","affiliation":[{"name":"In Vitro Drug Safety and BioTechnology, Department of Pharmacology, Institute of Drug Research, University of Toronto, South Tower of the MaRS Discovery Centre, 101 College Street, Toronto, ON M5G 1L5, Canada."},{"name":"Department of Pharmacology, University of Pretoria, Faculty of Health Sciences, Pretoria, South Africa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela Y.","family":"Jia","sequence":"additional","affiliation":[{"name":"In Vitro Drug Safety and BioTechnology, Department of Pharmacology, Institute of Drug Research, University of Toronto, South Tower of the MaRS Discovery Centre, 101 College Street, Toronto, ON M5G 1L5, Canada."},{"name":"Department of Pharmacology, University of Pretoria, Faculty of Health Sciences, Pretoria, South Africa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Steenkamp","sequence":"additional","affiliation":[{"name":"In Vitro Drug Safety and BioTechnology, Department of Pharmacology, Institute of Drug Research, University of Toronto, South Tower of the MaRS Discovery Centre, 101 College Street, Toronto, ON M5G 1L5, Canada."},{"name":"Department of Pharmacology, University of Pretoria, Faculty of Health Sciences, Pretoria, South Africa."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"155","reference":[{"key":"atypb1\/ref1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(85)90221-2"},{"key":"atypb2\/ref2","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/0031-9422(81)85124-2","volume":"20","author":"Birecka H.","year":"1981","journal-title":"Phytochemistry"},{"key":"atypb3\/ref3","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1111\/j.1939-165X.2005.tb00060.x","volume":"34","author":"Bondan C.","year":"2005","journal-title":"Vet. 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