Naslov
Membrane transporters of organic anions, cations, and water in experimental cisplatin nephrotoxicity

Autori
Ljubojević, Marija ; Breljak, Davorka ; Herak- Kramberger, Carol M ; Blanuša, Maja ; Rogić, Dunja ; Sabolić, Ivan

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Arhiv za higijenu rada i toksikologiju 64(2) / Kopjar, Nevenka - Zagreb : Institut za medicinska istraživanja i medicinu rada, 2013, 347-347

Skup
1. hrvatski simpozij o transporterima SOT-1

Mjesto i datum
Zagreb, Hrvatska, 06.06.2013. - 07.06.2013

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Domaća recenzija

Ključne riječi
aquaporins; CDDP; Western blotting; immunocytochemistry; organic anion transporters; organic cation transporters; rats

Sažetak
Antineoplastic cis-diaminodichloroplatinum (cisplatin, CDDP) is a highly nephrotoxic drug that causes hypoosmotic polyuria and decreased renal secretion of organic anions (OA) and cations (OC). The aim of this work was to investigate the expression of membrane proteins responsible for the transport of water (water channels/aquaporins, AQP1 and AQP2), OA (Oat1 and Oat3), and OC (Oct1 and Oct2) along the nephron in a rat model of cisplatin nephrotoxicity. Adult male Wistar rats were injected with a single dose of cisplatin (5 mg kg-1 b.m., i.p.) or 0.9 % NaCl (control), and tested for five consecutive days for urine excretion and standard biochemical parameters in urine. The animals were then sacrificed, the kidneys were sampled, and the platinum tissue content was determined by atomic absorption spectrometry. The expression of various transporters was studied using protein-specific polyclonal antibodies by Western blotting (WB) in isolated membranes and by immunofluorescence cytochemistry in tissue cryosections. In comparison with control animals, the cisplatin- treated rats exhibited hypoosmolar polyuria and a high accumulation of platinum in the kidney tissue. The abundance of AQP1, AQP2, Oat1, Oat3, Oct1, and Oct2 proteins in isolated renal membranes from the cisplatin-treated animals was strongly diminished. These WB findings were fully supported by immunocytochemical data. We conclude that the increased excretion of water (urine) OA and OC in cisplatin nephrotoxicity is caused by the downregulation of respective membrane transporters in epithelial cells along the nephron.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Farmacija

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