RGD Reference Report - Effects of serum lipoproteins on cyclosporine A cellular uptake and renal toxicity in vitro. - Rat Genome Database

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Effects of serum lipoproteins on cyclosporine A cellular uptake and renal toxicity in vitro.

Authors: Brocks, DR  Chaudhary, HR  Ben-Eltriki, M  Elsherbiny, ME  El-Kadi, AO 
Citation: Brocks DR, etal., Can J Physiol Pharmacol. 2014 Feb;92(2):140-8. doi: 10.1139/cjpp-2013-0250.
RGD ID: 11041167
Pubmed: PMID:24502637   (View Abstract at PubMed)
DOI: DOI:10.1139/cjpp-2013-0250   (Journal Full-text)

In-vitro studies were performed to shed light on previous findings that showed increased uptake of cyclosporine A in the kidneys and liver of hyperlipidemic rats, and increased signs of kidney toxicity. Hepatocytes were obtained from rats, cultured, and exposed to a diluted serum from hyperlipidemic rats. Some cells were also exposed to lipid-lowering drugs. After washing out the rat serum or lipid-lowering drugs, cells were exposed to cyclosporine A embedded in serum lipoproteins. Pretreatment with hyperlipidemic serum and lipid-lowering drugs was associated with an increased uptake of cyclosporine A. As expected, atorvastatin caused an increase in low density lipoprotein receptor and a decrease in MDR1A mRNA in the hepatocytes. A decrease in NRK-52E rat renal tubular cellular viability caused by cyclosporine A was noted when cells were preincubated with diluted hyperlipidemic serum. This was matched with evidence of hyperlipidemic-serum-associated increases in the NRK-52E cellular uptake of cyclosporine A and rhodamine-123. The findings of these experiments suggested that in hyperlipidemia the expression and (or) the functional activity of P-glycoprotein was diminished, leading to greater hepatic and renal uptake of cyclosporine A, and renal cellular toxicity.

Objects referenced in this article
Gene Abcb1a ATP binding cassette subfamily B member 1A Rattus norvegicus

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