title: Role of hydrogen peroxide in cyclosporine-induced renal tubular cell (LLC-PK1) injury.
abstract: We examined the role of hydrogen peroxide production in cyclosporine A (CsA)-induced LLC-PK1 injury. After exposure to CsA (0.1 microM - 100 microM), cytotoxicity assessed by lactate dehydrogenase release to the media increased dose-dependently. LLC-PK1 cells produced hydrogen peroxide, visualized by 2,7-dichlorodihydrofluorescein assay by the treatment with 100 microM CsA, that was blocked by the treatment with catalase. The cytotoxicity of CsA significantly decreased either by the treatment with catalase, mannitol, or deferoxamine, but not with superoxide dismutase. These results suggest the role of hydrogen peroxide as the source of hydroxyl radical, which mainly contributes to CsA-induced LLC-PK1 injury.
authors.affiliation: Division of Pediatrics, Children's Research Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan. mnishida@koto.kpu-mac.jp
authors.forename: Masashi
authors.initials: M
authors.lastname: Nishida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ogawa
authors.forename: Megumi
authors.initials: M
authors.lastname: Tamai
authors.forename: Kohhei
authors.initials: K
authors.lastname: Ishiwari
authors.forename: Kenji
authors.initials: K
authors.lastname: Hamaoka
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000009:adverse effects*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018374:LLC-PK1 Cells; D016877:Oxidants / Q000378:metabolism*; D013552:Swine
chemical_list: D007166:Immunosuppressive Agents; D016877:Oxidants; D016572:Cyclosporine; D006861:Hydrogen Peroxide