e-journal

Molecular biomarkers of phospholipidosis in rat blood and heart after amiodarone treatment

---

Phospholipidosis (PLD) is characterized by an intracellular accumulation of phospholipids in lysosomes and concurrent
development of concentric lamellar bodies. It is induced in humans and in animals by drugs with a cationic amphiphilic
structure. The purpose of the present study was to identify a set of molecular biomarkers of PLD in rat blood and heart, hypothetically applicable in preclinical screens within the drug development process. A toxicological study was set up in rats orally treated up to 11 days with 300mgkg–1 per day–1 amiodarone (AMD). Light and transmission electron microscopy investigations were performed to confirm the presence of lamellar bodies indicative of phospholipid accumulation. The effects ofAMD upon the transcriptome of these tissues were estimated using DNAmicroarray technology. Microarray data analysis showed that a total of 545 and 8218 genes were modulated byAMD treatment in heart and blood, respectively. Some genes implicated in the phospholipid accumulation in cells, such as phospholipase A2, showed similar alterations of gene expression. After transcriptome criteria of analysis and target selection, including also the involvement in the onset of PLD, 7 genes (Pla2g2a, Pla2g7, Gal, Il1b, Cebpb,Fcgr2b, Acer 2) were selected as candidate biomarkers of PLD in heart and blood tissues, and their potential usefulness as a sensitive screening test was screened and confirmed by quantitative Real-Time PCR analysis. Collectively, these data underscore the importance of ranscriptional profiling in drug discovery and development, and suggest blood as a surrogate tissue for possible
phospholipid accumulation in cardiomyocytes. Copyright © 2014 John Wiley & Sons, Ltd.

Keywords: phospholipidosis; rat; gene expression; blood; heart; amiodarone; toxicogenomics; surrogate

---

Ketersediaan

Tidak ada salinan data

Informasi Detail

Judul Seri

J. Appl. Toxicol.

No. Panggil

-

Penerbit

: John Wiley & Sons, Ltd.., 2015

Deskripsi Fisik

J. Appl. Toxicol. 2015; 35: 90–103

Bahasa

English

ISBN/ISSN

-

Klasifikasi

-

Tipe Isi

-

Tipe Media

-

Tipe Pembawa

-

Edisi

-

Subjek

FISIKA

Info Detail Spesifik

-

Pernyataan Tanggungjawab

Wati/Agus

Versi lain/terkait

Lampiran Berkas

Komentar

---

Anda harus masuk sebelum memberikan komentar