Effect Of Erdosteine On The Damage Of Hippocampal Neurones And Oxidative Stress In Rats With Seizures

ObjectiveTo study the influence of erdosteine to the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-P_x), the level of malondialdehyde (MDA) and neuronal damages in seizure rats' hippocampal neurons after seizure kindling induced by pentylenetertrazol. Investigate the functions of erdosteine about scavenging free radical and protecting neurons. Explore the mechanisms of erdosteine' s anticonvulsive effects, and the relationship between oxidative stress and neurons' apoptosis of rats with seizures.Methed1. Experimental animals and grouping: Wealth adult male SD rats were divided into there group randomly: PTZ group (n=10), erdosteine pre-disposal treatment group (n=10) and control group (n=10).2. Make seizure kindling model and pre-disposal treatment: Basic on the Dihel' s seizure kindling process and , make seizure kindling model by PTZ 50 mg/kg i.p. to PTZ group and erdosteine group , and use erdosteine 50 mg/kg i. p. to pre-disposal treatment before kindling for erdosteine group. Record the latent periods and seizure periods.3. Draw the materials and experiment Extract hippocampal neurons rapidly after all model animals' kindling, and assay the activities of SOD and GSH-P_x and the level of MDA by colorimetric method. Observe the hippocampal neurons ' damage by hematoxylin and eosin technique and terminal deoxynucleotidyl transferase dUTP nic-end labeling technique.Results1. All animals in PTZ group and erdosteine group were induced to seizure kindling, and seizure did not appear in rats in control group. The grade of onset was determined by Racine' s standard after kindle There was one rat died in the PTZ group, and it was eliminated. The seizure period of erdosteine group was significantly shorter than PTZ group, (P<0. 05), The latent period of erdosteine group was longer than PTZ group, but there was no significantly differences between them.2. To compare with normal group, the activities of SOD in both PTZ group and erdosteine group were lower, and PTZ group was significant much lower, ( P<0. 05). MDA level in PTZ group was higher than that in normal group, (P<0. 01), and there was no significantly change in erdosteine group. To compare with normal group, the activities of GSH-P_x in PTZ group were lower, ( P<0.01), and there was no significant distinguish between erdosteine group and control group.3. The results of HE stain: Neurons of hippocampus in the control group were normal microscopically with HE stain. In the PTZ group, acidophilic neurons identified with HE staining appeared dark and shrunken, with pyknotic nucleus, irregular dispersed chromatin clumps. There were less acidophilic neurons in the hippocampus of erdosteine group. There were significant differences, (P<0.01).The results of TUNEL stain: To compare with control group, PTZ group and erdosteine group were both had more TUNEL positive cells in the hippocampus, (P<0. 01). And there are much more TUNEL positive cells in PTZ group than those in erdosteine group, (P<0. 01).4. For PTZ group and erdosteine group, TUNEL positive cells have negative correlation with activities of SOD (r = -0.482, P<0. 05); TUNEL positive cells have positive correlation with MDA level (r = 0. 875, P<0. 01).ConclusionsErdosteine could reduce the oxidative stress level of rats with seizures. It also could reduce seizure periods, inhibit neuronal damage. Erdosteine have the effect of brain protection probably by scavenging free radical and reducing oxidative stress. Neurons' apoptosis has positive correlation with MDA level, and it has negative correlation with the activities of SOD.