Effect of pyridoxylidene aminoguanidine on human diploid cells B-HEF-2: in vitro cytotoxicity test and cytogenetic analysis.
BACKGROUND
Pyridoxylidene aminoguanidine is an appropriate inhibitor of protein glycation, respectively formation of advanced glycation products, which are connected with mechanism of pathogenesis in chronic diabetic complications. Moreover, it was found that in comparison with aminoguanidine, pyridoxylidene aminoguanidine does not influence the level of vitamin B6 in liver and kidneys in vivo. The aim of this study was to test cytotoxic effect of pyridoxylidene aminoguanidine in vitro, in regard to its potential use as inhibitor of advance protein glycation in diabetic patients.


METHODS
The potential genotoxic activity of pyridoxylidene aminoguanidine in vitro was assessed by the micronucleus test and the karyological analysis. The direct contact method using diploid human cell line B-HEF-2 was performed to evaluate cytotoxicity. The concentrations of 5 x 10(-3), 2.5 x 10(-3) and 1 x 10(-3) ml/l were used in all tests.


RESULTS
Microscopic analysis did not proved any changes in morphology of exposed fibroblasts. The inhibitive effect of pyridoxylidene aminoguanidine was increased with rising concentration. The proliferative activity of exposed cells to concentrations of 1 x 10(-3), 2.5 x 10(-3), 5 x 10(-3) mol/l was inhibited approximately by 30%, 60% and 80%, respectively. The frequency of micronuclei and rate of numerical or structural aberrations was not increased.


CONCLUSIONS
Obtained results confirmed that pyridoxylidene aminoguanidine in selected concentrations has an inhibitive effect on the proliferation activity of exposed cells, but did not develop any cytotoxic effect on B-HEF-2 cells.
Comenius University in Bratislava, Faculty of Medicine, Institute of Medical Biology and Genetics, Sasinkova 4, 813 72 Bratislava, Slovak Republic.
Ján
J
Vojtassák
Jozef
J
Cársky
L'ubos
L
Danisovic
Daniel
D
Böhmer
Milan
M
Blasko
Tatiana
T
Braxatorisová
D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002869:Chromosome Aberrations; D004171:Diploidy; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects; D006146:Guanidines / Q000633:toxicity*; D006801:Humans; D015162:Micronucleus Tests; D011732:Pyridoxal Phosphate / Q000633:toxicity
D006146:Guanidines; D011732:Pyridoxal Phosphate; C004479:pimagedine