The third multidisciplinary conference on drug research, Piła 2002. Effects of 1alpha,25-dihydroxyvitamin D3 and some putative steroid neuroprotective agents on the hydrogen peroxide-induced damage in neuroblastoma-glioma hybrid NG108-15 cells.
Steroids are implicated in the regulation of neurodegenerative processes including oxidative stress. The aim of this study was to compare the effects of 1alpha,25-dihydroxyvitamin D3 (calcitriol) and its low-calcemic analogue (24R)-1,24-dihydroxycholecalciferol (tacalcitol, PRI-2191) and some putative neuroprotective steroids belonging to various pharmacological groups on the hydrogen peroxide-induced cytotoxicity in NG108-15 cell line. Both secosteroids prevented in a concentration-dependent manner (50-500 nM) the hydrogen peroxide-induced lactate dehydrogenase release in the NG108-15 cells. Estrogens (17beta-estradiol and estriol, 100 and 1000 nM) also protected these cells. Of the two neurosteroids tested at micromolar concentrations, dehydroepiandrosterone sulphate markedly reduced cell damage, whereas the allopregnanolone showed a weak neuroprotective effect. These data support some previous observations on the antineurotoxic action of neurosteroids and indicate that calcitriol and its low-calcemic analogue PRI-2191 have neuroprotective properties comparable to those of estrogens. Considering the undesired effects of estrogens, it seems that some calcitriol analogues may be alternative drugs in the treatment of some oxidative stress-related neurodegenerative disorders.
Department of Endocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Str., 31-343 Kraków, Poland.
Magdalena
M
Tetich
Monika
M
Leśkiewicz
Bogusława
B
Budziszewska
Agnieszka
A
Basta-Kaim
Andrzej
A
Kutner
Władysław
W
Lasoń
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D004100:Dihydroxycholecalciferols / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D004964:Estriol / Q000494:pharmacology; D005910:Glioma; D006822:Hybrid Cells; D006861:Hydrogen Peroxide / Q000633:toxicity; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D009447:Neuroblastoma; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D011280:Pregnanolone / Q000494:pharmacology; D051381:Rats; D013256:Steroids / Q000494:pharmacology*
D004100:Dihydroxycholecalciferols; D018696:Neuroprotective Agents; D013256:Steroids; D003687:Dehydroepiandrosterone; D004958:Estradiol; C023850:1 alpha,24-dihydroxyvitamin D3; D006861:Hydrogen Peroxide; D011280:Pregnanolone; D007770:L-Lactate Dehydrogenase; D004964:Estriol; D002117:Calcitriol