The effect of nordihydroguaiaretic acid on iodoacetate-induced toxicity in cultured neurons.
Nordihydroguaiaretic acid (NDGA) is present in high concentrations in the desert shrub Creosote bush, Larrea tridentate. This plant has been used in traditional medicine because of its beneficial effects related, at least in part, to its antioxidant properties. Taking into account some evidence about neuroprotective effects elicited by NDGA, we evaluated the effect of this compound on the neurotoxicity induced by iodoacetate (IAA), an inhibitor of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), on cerebellar granule neurons. In addition, as reactive oxygen species play an important role in IAA-induced cytotoxicity, we also studied the enzymatic antioxidant system in IAA-treated cells. We found that IAA caused a dose-dependent decrease in cell viability of cultured neurons with an IC(50) of 18.4 microM and induced increased activity of catalase, glutathione peroxidase, and glutathione-S-transferase. Moreover, NDGA attenuated the toxicity induced by 18.4, 25, and 30 microM of IAA without abolishing the inhibitory effect of IAA on GAPDH activity. Furthermore, NDGA could prevent the inhibitory effect of IAA on aconitase activity, a marker of oxidative stress, suggesting that the protective effect of NDGA on IAA neurotoxicity was associated with the prevention of oxidative stress.
Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México CP 04510, México DF, México.
Noemí
N
Cárdenas-Rodríguez
Silvia
S
Guzmán-Beltrán
Omar Noel
ON
Medina-Campos
Marisol
M
Orozco-Ibarra
Lourdes
L
Massieu
José
J
Pedraza-Chaverri
D000818:Animals; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors; D007461:Iodoacetates / Q000633:toxicity*; D009637:Masoprocol / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology
D004791:Enzyme Inhibitors; D007461:Iodoacetates; D009637:Masoprocol; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases