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

Toshihiko Tsutsumi; Syougo Yamakawa; Akira Ishihara; Aimi Yamamoto; Tamotsu Tanaka; Akira Tokumura

doi:10.1016/j.toxrep.2015.02.012

Toxicology Reports (Jan 2015)

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

Toshihiko Tsutsumi,
Syougo Yamakawa,
Akira Ishihara,
Aimi Yamamoto,
Tamotsu Tanaka,
Akira Tokumura

Affiliations

Toshihiko Tsutsumi: Department of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Japan
Syougo Yamakawa: Department of Pharmaceutical Health Chemistry, Institute of Health Biosciences, University of Tokushima Graduate School, Japan
Akira Ishihara: Department of Anatomic Pathology, Prefectural Nobeoka Hospital, Japan
Aimi Yamamoto: Department of Pharmaceutical Health Chemistry, Institute of Health Biosciences, University of Tokushima Graduate School, Japan
Tamotsu Tanaka: Department of Pharmaceutical Health Chemistry, Institute of Health Biosciences, University of Tokushima Graduate School, Japan
Akira Tokumura: Department of Pharmaceutical Health Chemistry, Institute of Health Biosciences, University of Tokushima Graduate School, Japan

DOI: https://doi.org/10.1016/j.toxrep.2015.02.012
Journal volume & issue: Vol. 2, no. C
pp. 121 – 129

Abstract

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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.

Published in Toxicology Reports

ISSN: 2214-7500 (Online)
Publisher: Elsevier
Country of publisher: Ireland
LCC subjects: Medicine: Public aspects of medicine: Toxicology. Poisons
Website: http://www.journals.elsevier.com/toxicology-reports/

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