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Articles in PresS, published online ahead of print December 3, 2002
Am J Physiol Renal Physiol, 10.1152/ajprenal.00327.2002
Submitted on September 9, 2002
Accepted on November 27, 2002
1 Department of Pharmacodynamics, Medical Academy, Bialystok, Poland
2 Department of Clinical Pathology, Medical Academy, Bialystok, Poland
3 Department of Cardiosurgery, Medical Academy, Bialystok, Poland
4 Department of Gyanecological Endocrinology, Medical Academy, Bialystok, Poland
* To whom correspondence should be addressed. E-mail: dariuszpawlak{at}poczta.onet.pl.
Quinolinic acid (QA) is a potent endogenous excitotoxin, elevation of its concentration in organism has been implicated in the pathogenesis of various disorders. The aim of the study was the assessment of quinolinic acid (QA) impact on the process of erythropoiesis. Marked increase of QA concentration was observed in plasma and peripheral tissues of uremic rats. These changes were proportional to the amount of the removed renal tissue and positively correlated with the concentration of creatinine, but negatively correlated with hematological parameters: hematocrit, hemoglobin red blood cells count. The changes were accompanied by a slight decrease in the concentration of endogenic erythropoietin (EPO) in plasma of animals with uremia. Chronic treatment with QA diminished the increase in EPO concentration after cobalt in rats. These changes were associated with the decrease in all hematological parameters after QA administration. The in vitro study in the conditions of hypoxia showed that QA inhibited the EPO release from HepG2 cells to the culture base. Additionally, in HepG2 cells QA had a dose-dependent inhibitory effect on hypoxia- and cobalt- induced EPO gene expression without any cell toxicity. In conclusion, the erythropoiesis in CRF could be attributed to the influence of QA on EPO synthesis. Thus, we propose, that QA can be an uremic toxin responsible for anemia in animals or patients with renal failure.
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