Mechanism of inhibitory effect of 3-hydroxykynurenine on erythropoiesis in patients with renal insufficiency.
Increase of 3-hydroxykynurenine (3-HKYN) concentration was observed in plasma patients with chronic renal insufficiency (CRI). These changes positively correlated with the concentration of creatinine, but negatively correlated with haematological parameters: haematocrit, haemoglobin and red blood cells count. The changes were accompanied by a slight decrease of the concentration of erythropoietin (EPO) in plasma of patients with CRI. The "in vitro" study in the conditions of hypoxia showed that 3-HKYN inhibited the release of EPO from HepG2 cells to the culture base. In conclusion, the erythropoiesis in CRI could be attributed to the influence of 3-HKYN on EPO synthesis. Thus, we propose that 3-HKYN can be an uraemic of toxin partially responsible for anaemia patients with CRI.
Pawlak
Dariusz
D
Department of Pharmacodynamics, Medical Academy, Mickiewicza 2C, 15-230 Bialystok, Poland. dariuszpawlak@poczta.onet.pl
Koda
Mariusz
M
Wołczyński
Sawomir
S
Myśliwiec
Michal
M
Buczko
Wlodzimierz
W
D000328:Adult; D000368:Aged; D000740:Anemia / Q000097:blood / Q000209:etiology; D016022:Case-Control Studies; D002460:Cell Line; D004920:Erythropoiesis / Q000187:drug effects* / Q000502:physiology; D004921:Erythropoietin / Q000097:blood; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications; D007737:Kynurenine / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged
D004921:Erythropoietin; C005045:3-hydroxykynurenine; D007737:Kynurenine