Does allopurinol prevent side effects of cyclosporine-A treatment?

Kobelt, Viola; Heß, T; Matzkies, F; Gerhardt, Ulf; Hillebrand, Uta; Suwelack, Barbara; Sindermann, Juergen R.; Hohage, Helge

doi:10.1016/s0041-1345(02)02913-5

Cited by 6 publications

(5 citation statements)

References 17 publications

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“…Chronic cyclosporine use, and to a lesser extent, tacrolimus, are associated with the development of hyperuricemia, renal vasoconstriction, hypertension and a renal lesion characterized by afferent arteriolar hyalinosis and tubulointerstitial fibrosis. Interestingly, the administration of allopurinol (a xanthine-oxidase inhibitor which lowers uric acid) to rats can attenuate both the renal vasoconstriction and the decrease in glomerular filtration rate induced by cyclosporine [31,32]. Furthermore, chronic cyclosporine nephropathy is very similar to what has been observed in normal rats simply by raising uric acid levels [26].…”

Section: Reviewmentioning

confidence: 89%

Could Uric acid have a Pathogenic Role in Chronic Allograft Dysfunction?

Mazzali¹,

Kazamel²,

Johnson³

2010

Arab J. Nephr. Trans

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Section: Reviewmentioning

confidence: 89%

Could Uric acid have a Pathogenic Role in Chronic Allograft Dysfunction?

Mazzali¹,

Kazamel²,

Johnson³

2010

Arab J. Nephr. Trans

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“…Uric acid is also implicated in activation of B cells and IL-2 receptor on monocyte via MyD88 dependent signaling pathway [11][12][13] . Antigen independent mechanisms include interaction with cyclosporine [14][15][16][17][18] , stimulation of smooth muscle cell and association with hypertension, insulin resistance and dyslipidemia [19][20][21][22][23] Hyperuricemia occurs early after transplantation and is associated with decreased GFR. Recent studies investigating the association between increased uric acid and graft dysfunction have suggested that hyperuricemia may contribute to the progressive deterioration of graft function and ultimately to the graft loss 2,24,25 .Cyclosporine and to some extent tacrolimus used in transplant recipients causes renal vasoconstriction, hypertension and hyperuricemia.…”

Section: Introductionmentioning

confidence: 99%

A retrospective study of hyperurecemia in renal transplant recipients

Baruah

Datta

Nath

et al. 2014

Int Jour of Biomed Res

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“…[3][4][5] The brain in many aspects differs from the other organs of the body; particularly because it is completely separated from the systemic circulation by the bloodbrain barrier (BBB) and haemato-cerebrospinal (HCE) barriers. 6) P-glycoprotein (Pgp) is expressed in the luminal face of the BBB endothelial cells membrane.…”

mentioning

confidence: 99%

Effect of Tacrolimus on Activity and Expression of P-Glycoprotein and ATP-Binding Cassette Transporter A5 (ABCA5) Proteins in Hematoencephalic Barrier Cells

Quezada

Garrido

González-Oyarzún

et al. 2008

Biological & Pharmaceutical Bulletin

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Tacrolimus (FK506) is widely used as an immunosuppressor in clinical practice; nonetheless a great part of its mechanisms of action and the processes triggering side effects remain unknown.1) A wide spectrum of adverse effects including neurotoxic, nephrotoxic, gastrointestinal, metabolic and hematological effects have been reported associated with tacrolimus.2) The major central nervous system (CNS) complications induced by this calcineurin inhibitor include headaches, altered mental status (AMS), seizures, cortical blindness, auditory and visual hallucinations, spasticity, paresis, and ataxia.3-5) The brain in many aspects differs from the other organs of the body; particularly because it is completely separated from the systemic circulation by the bloodbrain barrier (BBB) and haemato-cerebrospinal (HCE) barriers.6) P-glycoprotein (Pgp) is expressed in the luminal face of the BBB endothelial cells membrane. 7) A relevant role of Pgp in the extrusion of toxic metabolites from brain and the impairment of drugs to cross the hematoencephalic barrier has been determined using culture of brain capillary endothelial cells and Pgp knockout mice. [8][9][10][11][12][13] Substantial increases in the concentration of vinblastine, paclitaxel and doxorubicin were found in brains of knockout mice. These findings are probably due to the drug removal function exerted by this ATP-dependent efflux pump, also associated with the multidrug resistance (MDR) phenomenon.6) In humans, Pgp is encoded by two genes MDR1 and MDR3 the first being associated with MDR phenotype.14) The participation of MDR3 P-glycoprotein in multidrug resistance has been suggested by numerous studies; however, the rate of MDR3 P-glycoprotein-mediated transport is low for most drugs, and is not detectable due to its low expression rate. [15][16][17] The expression of other two ATP-binding cassette (ABC) type transporters, ABCA2 and ABCA5, was also detected in human brain capillary cells.18) ABCA2 was related to cholesterol and phospholipids remodelling function in neurons and glial cells, while ABCA5 lacks a recognized function in brain. 19) An effect of tacrolimus on multiple resistance to drugs was early observed in lymphoblastic leukemia cell lines leading to an increase in the intracellular accumulation and therefore cytotoxicity of chemotherapeutic agents. 20) In addition, other studies indicate that tacrolimus works as a substrate for Pgp.21) Although many of tacrolimus mechanisms of action and processes triggering neurotoxicity are still unknown, we proposed to explore the possibility that the side effects of tacrolimus at blood concentrations Ն30 ng/ml, could be linked to the functional blockade and variations in the expression levels of MDR proteins, such as MDR1, and probably ABCA5 in BBB cells. MATERIALS AND METHODS Cells CultureThe immortalized human brain microvascular endothelial cells, HBMEC, used in this study were kindly provided by Dr. Kwang Sik Kim (Johns Hopkins University, Baltimore, U.S.A.). The cells were grown in RPMI 1640 medium suppl...

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Does allopurinol prevent side effects of cyclosporine-A treatment?

Cited by 6 publications

References 17 publications

Could Uric acid have a Pathogenic Role in Chronic Allograft Dysfunction?

Could Uric acid have a Pathogenic Role in Chronic Allograft Dysfunction?

A retrospective study of hyperurecemia in renal transplant recipients

Effect of Tacrolimus on Activity and Expression of P-Glycoprotein and ATP-Binding Cassette Transporter A5 (ABCA5) Proteins in Hematoencephalic Barrier Cells

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