title: Dual role of acetaminophen in promoting hepatoma cell apoptosis and kidney fibroblast proliferation.
abstract: Acetaminophen (APAP), is a safe analgesic and antipyretic drug at therapeutic dose, and is widely used in the clinic. However, high doses of APAP can induce hepatotoxicity and nephrotoxicity. Most studies have focused on high‑dose APAP‑induced acute liver and kidney injury. So far, few studies have investigated the effects of the therapeutic dose (1/10 of the high dose) or of the low dose (1/100 of the high dose) of APAP on the cells. The aim of this study was to investigate the cellular effects of therapeutic- or low‑dose APAP treatment on hepatoma cells and kidney fibroblasts. As expected, high‑dose APAP treatment inhibited while therapeutic and low‑dose treatment did not inhibit cell survival of kidney tubular epithelial cells. In addition, therapeutic-dose treatment induced an increase in the H2O2 level, activated the caspase‑9/‑3 cascade, and induced cell apoptosis of hepatoma cells. Notably, APAP promoted fibroblast proliferation, even at low doses. This study demonstrates that different cellular effects are exerted upon treatment with different APAP concentrations. Our results indicate that treatment with the therapeutic dose of APAP may exert an antitumor activity on hepatoma, while low‑dose treatment may be harmful for patients with fibrosis, since it may cause proliferation of fibroblasts.
authors.affiliation: Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University, Taichung 404, Taiwan, R.O.C.
authors.forename: Yung-Luen
authors.initials: YL
authors.lastname: Yu
authors.affiliation: Department of Emergency Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei 231, Taiwan, R.O.C.
authors.forename: Giou-Teng
authors.initials: GT
authors.lastname: Yiang
authors.affiliation: Division of Allergy‑Immunology‑Rheumatology, Department of Internal Medicine, Saint Mary's Hospital Luodong, Yilan 265, Taiwan, R.O.C.
authors.forename: Pei-Lun
authors.initials: PL
authors.lastname: Chou
authors.affiliation: Division of General Surgery, Taichung Hospital, Ministry of Health and Welfare, Taichung 403, Taiwan, R.O.C.
authors.forename: Hsu-Hung
authors.initials: HH
authors.lastname: Tseng
authors.affiliation: 2The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University, Taichung 404, Taiwan, R.O.C.
authors.forename: Tsai-Kun
authors.initials: TK
authors.lastname: Wu
authors.affiliation: Department of Nutrition, Master Program of Biomedical Nutrition, Hungkuang University, Taichung 433, Taiwan, R.O.C.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Hung
authors.affiliation: Department of Nutrition, Master Program of Biomedical Nutrition, Hungkuang University, Taichung 433, Taiwan, R.O.C.
authors.forename: Pei-Shiuan
authors.initials: PS
authors.lastname: Lin
authors.affiliation: Department of Nutrition, Master Program of Biomedical Nutrition, Hungkuang University, Taichung 433, Taiwan, R.O.C.
authors.forename: Shu-Yu
authors.initials: SY
authors.lastname: Lin
authors.affiliation: Department of Nursing, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei 231, Taiwan, R.O.C.
authors.forename: Hsiao-Chun
authors.initials: HC
authors.lastname: Liu
authors.affiliation: Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University, Taichung 404, Taiwan, R.O.C.
authors.forename: Wei-Jung
authors.initials: WJ
authors.lastname: Chang
authors.affiliation: Department of Nutrition, Master Program of Biomedical Nutrition, Hungkuang University, Taichung 433, Taiwan, R.O.C.
authors.forename: Chyou-Wei
authors.initials: CW
authors.lastname: Wei
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000166:cytology; D007684:Kidney Tubules / Q000166:cytology; D051381:Rats
chemical_list: D000082:Acetaminophen; D053148:Caspase 3; D053453:Caspase 9