Effect of iron and lipid peroxidation on development of cerebellar granule cells in vitro

The aim of this study was to investigate the effect of chelated ferric ion on neuronal development in vitro using cultured cerebellar granule cells of the rat. The cells were exposed to ferric nitrilotriacetate at varying concentrations for seven or 14 days. In addition to morphological studies, protein content determination and malondialdehyde measurement were performed. The study showed that cell development, with the addition of a lower concentration of chelated ferric ion (5 microM), could be kept in a normal condition, no significant changes in protein content and malondialdehyde production being found as compared with those of the controls, while the addition of higher concentrations of chelated ferric ion (> or = 10 microM) to the cultures demonstrated an adverse effect on development of cerebellar granule cell in vitro. Determination of protein content showed that the neuronal population decreased significantly, and the neuronal loss was inversely proportional to the iron concentrations added. Malondialdehyde measurement demonstrated that the extent of lipid peroxidation reaction increased remarkably with increasing iron concentration. A very close and highly significant correlation (gamma=0.985) between changes of malondialdehyde production and protein content was observed. These results suggest that the neuronal loss in the cultures with higher concentrations of iron was due to lipid peroxidation reaction induced by the addition of iron, and that iron overload might accelerate the process of ageing and death of cerebellar granule cells in vitro.