LETHALITY PERCENTILE DOSES, BIOACCUMULATION OF NANOALUMINA AND EVALUATION OF ITS TOXICITY ON THE GLUTAMATE-GABA SYSTEM IN THE HIPPOCAMPUS OF MALE ALBINO RATS

Abstract

This study was aimed to estimate the lethality percentile doses and accumulation of nanoalumina (Al2O3 nanoparticles, average diameter 9.4±1.6 nm) in the hippocampus and to evaluate its potential neurotoxicity to the glutamate-GABA system, following intranasal-instillation, at acute and sub-lethal terms of experiments. The computed lethality percentile doses found that the median lethal doses (LD50) at 24, 48, 72 and 96 hours were 9.42, 7.80, 6.73 and 6.09 g/kg body weight, respectively. In acute experiments, male albino rats were instilled with a single dose of 0 g, 3.2 g, 4.4 g and 5.5 g of nanoalumina/kg body weight, respectively. In sub-lethal experiments, rats were daily instilled with a sub-lethal dose of 0.6 g/kg body weight for 14 days. Bioaccumulation of aluminum in the hippocampus, were positively correlated with the instilled doses (in acute experiments) and the experimental periods (in sub-lethal experiments) and its mean levels were higher than the corresponding controls. In both terms of the experiments, the levels of the glutamate were significantly higher than the controls, whereas levels of gamma-amino butyric acid (GABA) were markedly depleted. The levels of glutamate exhibited a direct relationship with the accumulated aluminum, whereas the GABA showed a negative correlation. Levels of glutamate and the ratio of glutamate/GABA were correlated positively with the instilled acute doses and the experimental periods, whereas GABA showed a negative correlation. On the other hand, the levels of GABA were inversely proportion with levels of glutamate, in acute and sub-lethal terms. In conclusion, bioaccumulation of nanoalumina was dose- and time-dependent, and strongly correlated with the excitotoxicity in the hippocampus.