title: The potential protective role of lysophospholipid mediators in nephrotoxicity induced by chronically exposed cadmium.
abstract: Cadmium is a hazardous metal whose chronic exposure induces renal failure due to fibrosis, but the mechanisms are not well known. In this study we analyzed the molecular species of lysophosphatidic acid (LPA) and related phospholipids, together with their metabolic enzyme activity, in plasma from Wistar rats exposed up to 300ppm Cd(2+) in drinking water for 114days. Exposure of 300ppm Cd(2+) for 114days enhanced autotoxin (ATX)/lysophospholipase D activity, but significantly lowered the total levels of LPA and lysophosphatidylethanolamine. Interestingly, the total level of sphingosine-1-phosphate (S1P) was elevated dose-dependently by Cd(2+). Cultured rat kidney-derived interstitial fibroblast cells, NRK49F cells and proximal epithelial cells, NRK52E cells, were both responsive to the protective action of LPA or S1P against Cd(2+) toxicity. The former cell expresses ATX RNA. In conclusion, the elevation of LPA-producing enzyme activity and S1P concentrations in plasma after exposure of rats to Cd(2+) would protect from the renal toxicity of Cd(2+).
authors.affiliation: Department of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Tsutsumi
authors.affiliation: Department of Anatomic Pathology, Prefectural Nobeoka Hospital, Miyazaki, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ishihara
authors.affiliation: Department of Pharmaceutical Health Chemistry, Institute of Health Biosciences, University of Tokushima Graduate School, Japan.
authors.forename: Aimi
authors.initials: A
authors.lastname: Yamamoto
authors.affiliation: Department of Pharmaceutical Health Chemistry, Institute of Health Biosciences, University of Tokushima Graduate School, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Asaji
authors.affiliation: Department of Pharmaceutical Health Chemistry, Institute of Health Biosciences, University of Tokushima Graduate School, Japan.
authors.forename: Syougo
authors.initials: S
authors.lastname: Yamakawa
authors.affiliation: Department of Pharmaceutical Health Chemistry, Institute of Health Biosciences, University of Tokushima Graduate School, Japan. Electronic address: Tokumura@tokushima-u.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Tokumura
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D001483:Base Sequence; D001835:Body Weight / Q000187:drug effects; D002104:Cadmium / Q000633:toxicity*; D002853:Chromatography, Liquid; D017931:DNA Primers; D007668:Kidney / Q000187:drug effects*; D008246:Lysophospholipids / Q000502:physiology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053719:Tandem Mass Spectrometry
chemical_list: D017931:DNA Primers; D008246:Lysophospholipids; D002104:Cadmium
keywords: Cadmium; Lysophosphatidic acid; NRK49F cells; NRK52E cells; Renal failure; Sphingosine-1-phosphate