Reduced kidney levels of lysophosphatidic acids in rats after chronic administration of aristolochic acid: Its possible protective role in renal fibrosis

Toxicology Reports

Akira Ishihara¹  Akira Tokumura²  Syougo Yamakawa²  Aimi Yamamoto²  Tamotsu Tanaka²  Toshihiko Tsutsumi³ 

[1] Department of Anatomic Pathology, Prefectural Nobeoka Hospital, Japan;Department of Pharmaceutical Health Chemistry, Institute of Health Biosciences, University of Tokushima Graduate School, Japan;Department of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Japan;

关键词: Lysophospholipid;    Aristolochic acid;    Lysophosphatidic acid;    Chronic kidney disease;    Fibrosis;    Nephrotoxicity;   

DOI  :  10.1016/j.toxrep.2015.02.012

来源: DOAJ

【 摘 要 】

Aristolochic acid (AA) is considered to be a causative agent for progressive interstitial renal fibrosis, leading to AA nephropathy. Lysophosphatidic acid (LPA) is a mediator in the onset of renal fibrosis. In this study, we analyzed the molecular species of LPA and its precursor lysophospholipids in kidney tissue from rats exposed to AA. Daily intraperitoneal injections of AA for 35 days to rats gave rise to fibrosis in kidney, decreased the kidney levels of LPA, lysophosphatidylserine and lysophosphatidylinositol. In rat renal cell lines (NRK52E and NRK49F), AA-induced cytotoxicity was potentiated by Ki16425, LPA1,3 receptor antagonist. The level of mRNA encording α-smooth muscle actin was significantly increased by AA-treatment only in NRK52E cells, while the mRNA level of collagen III was decreased in both NRK52E and NRK49F cells. These results suggest that endogenous LPA in rat kidney prevents AA-induced renal fibrosis.

【 授权许可】

Unknown