Role of hydrogen peroxide in cyclosporine-induced renal tubular cell (LLC-PK1) injury.
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.
Nishida
Masashi
M
Division of Pediatrics, Children's Research Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan. mnishida@koto.kpu-mac.jp
Ogawa
Hiroshi
H
Tamai
Megumi
M
Ishiwari
Kohhei
K
Hamaoka
Kenji
K
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
D007166:Immunosuppressive Agents; D016877:Oxidants; D016572:Cyclosporine; D006861:Hydrogen Peroxide