Primary culture of proximal tubular cells from normal rat kidney as an in vitro model to study mechanisms of nephrotoxicity

Boogaard, Peter J.; Zoeteweij, J. Paul; Berkel, Theo J.C. Van; Noordende, J. M. van't; Mulder, Gerard J.; Nagelkerke, J. Fred

doi:10.1016/0006-2952(90)90010-i

Cited by 34 publications

(11 citation statements)

References 25 publications

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“…As reported for other drugs (including the anaesthetic benzyl alcohol), cDDP and CBDCA could modify apical membrane fluidity at non-cytotoxic concentrations, a phenomenon which has been involved in modulation of both phosphate and glucose carriers resulting from a change in the physical state of their lipid environment (Friedlander et al 1990). These data, in conjunction with those obtained with rat proximal tubule cells in primary culture (Boogaard et al 1990), suggest that MGP transport could be an appropriate parameter to monitor functional damage induced by cDDP and CBDCA in RPT cells at non-cytotoxic concentrations. These data, in conjunction with those obtained with rat proximal tubule cells in primary culture (Boogaard et al 1990), suggest that MGP transport could be an appropriate parameter to monitor functional damage induced by cDDP and CBDCA in RPT cells at non-cytotoxic concentrations.…”

Section: Discussionsupporting

confidence: 54%

Platinum complex-induced dysfunction of cultured renal proximal tubule cells

et al. 1993

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Platinum coordination complexes (PtCx) are potent against several types of cancer but are often nephrotoxic. With a view to developing a PtCx nephrotoxicity model, the toxicity of cisplatin (cDDP), transplatin (tDDP) and carboplatin (CBDCA) was studied in primary cultures of rabbit proximal tubule (RPT) cells and in the renal epithelial OK cell line. The cytotoxicity of these PtCx (10-3000 microM) was assessed after 24 h exposure of confluent monolayers in terms of LDH release; their effects at non-cytotoxic concentrations (1-1000 microM) on DNA and protein synthesis, glucose transport, marker enzymes and the total glutathione concentration were also determined, together with cellular platinum uptakes. The cytotoxicity ranking of the studied compounds differed for OK and RPT cells (cDDP > tDDP; cDDP > CBDCA and tDDP > cDDP; cDDP > CBDCA, respectively). Only results which were obtained in RPT cells corresponded to reported nephrotoxicity in vivo, making OK cells inappropriate for the study of PtCx nephrotoxicity in vitro. cDDP was about 10 times less cytotoxic for OK cells than for RPT cells because of lower cellular uptake. tDDP was unable markedly to inhibit biochemical and functional parameters in RPT cells below cytotoxic concentrations. At non-cytotoxic concentrations, cDDP and CBDCA depressed synthetic activity (mainly DNA) and, to a lesser extent, Na(+)-K(+)-ATPase activity and glucose transport in RPT cells. Total glutathione levels in RPT cells steadily increased during exposure to cDDP, tDDP and CBDCA, before the onset of cell death, arguing against an early role of glutathione depletion in PtCx toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionsupporting

confidence: 54%

Platinum complex-induced dysfunction of cultured renal proximal tubule cells

et al. 1993

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“…These cells in primary culture retain morphological polarity, exhibiting numerous microvilli at the apical side and having tight junctions, without immortalization or dedifferentiation [30]. In addition, it was confirmed that primary-cultured PTCs retain active transport systems for organic ions, as well as enzyme systems [31][32][33]. …”

Section: Introductionmentioning

confidence: 85%

Transport characteristics of L‐citrulline in renal apical membrane of proximal tubular cells

Mitsuoka

Shirasaka

Fukushi

et al. 2009

Biopharm & Drug Disp

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L-Citrulline has diagnostic potential for renal function, because its plasma concentration increases with the progression of renal failure. Although L-citrulline extracted by glomerular filtration in kidney is mostly reabsorbed, the mechanism involved is not clearly understood. The present study was designed to characterize L-citrulline transport across the apical membranes of renal epithelial tubular cells, using primary-cultured rat renal proximal tubular cells, as well as the human kidney proximal tubular cell line HK-2. L-Citrulline was transported in a Na(+)-dependent manner from the apical side of both cell types cultured on permeable supports with a microporous membrane. Kinetic analysis indicated that the transport involves two distinct Na(+)-dependent saturable systems and one Na(+)-independent saturable system in HK-2 cells. The uptake was competitively inhibited by neutral and cationic, but not anionic amino acids. Relatively large cationic and anionic compounds inhibited the uptake, but smaller ones did not. In HK-2 cells, mRNA expression of SLC6A19 and SLC7A9, which encode B(0)AT1 and b(0,+)AT, respectively, was detected by RT-PCR. In addition, L-citrulline transport was significantly decreased in HK-2 cells in which either SLC6A19 or SLC7A9 was silenced. Hence, these results suggest that amino acid transporters B(0)AT1 and b(0,+)AT are involved in the reabsorption of L-citrulline in the kidney, at least in part, by mediating the apical membrane transport of L-citrulline in renal tubule cells.

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“…In addition, they can be maintained for several days without redifferentiation. [22] The RTEC in culture retains active transport systems for organic ions and D-glucose as well as many enzyme systems, like GGT, cysteinayl-glycinase, beta-lyase, and acrylase, which are essential for the expression of toxicity in the PTC, primary cultures faithfully reflect the toxicological susceptibilities that occur in freshly isolated cells and presumably, in the whole animal. [23] The earlier information makes primary cell cultures the systems of our choice to investigate the difference in CP toxicity in intact animals.…”

Section: Discussionmentioning

confidence: 96%