Comparative Pathomorphological Analysis of the New Spirofused Heterocyclic Compounds Toxic Effects on the Rat Hippocampus

The aim was to conduct a comparative pathomorphological analysis of the toxic effects of new spirofused heterocyclic compounds on the rat hippocampus. Material and methods. Male Wistar rats were divided into 3 groups. Animals of the control group were injected with 1 ml of saline solution, rats of the 1st experimental group (EG1) were given a single intraperitoneal injection of a spirofused barbiturate, animals of the 2nd experimental group (EG2) were administered a spirofused oxindole at a dose of 12 mg/kg of the animal’s body weight, also in a volume of 1 ml. 2 and 8 weeks after administration of the drugs, the animals were taken out of the experiment. Using standard histological techniques, 5 μm thick sections were stained with toluidine blue using the Nissl method. Immunocytochemical detection of astrocytic glia was performed using antibodies to the GFAP protein. Results. In both experimental groups, pyramidal neurons undergo morphological changes typical for dying cells. Moreover, in animals from EG2, compared to the control group, degenerative changes were detected in a larger number of neurons and in all fields of the hippocampus, while in EG1, fields CA1 and CA3 were predominantly affected. Comparison between EG1 and EG2 showed that the spirofused oxindole has a greater toxic effect on the CA3 and CA4 fields. It was established that in EG1, morphometric parameters normalized by the 8th week of the experiment, while in EG2 they never returned to control values. It was found that, despite the obvious death of neurons, proliferation and activation of astroglia in the pyramidal layer does not occur. In contrast, the number of astrocytes significantly decreased in both experimental groups compared to the control group. In EG2, the number of astrocytes in the pyramidal layer on the 2nd week of the experiment significantly differed from those in EG1. Conclusion. Spirofused barbiturate and spirofused oxindole penetrate the blood-brain barrier, cause morphological changes in pyramidal neurons in all areas of the hippocampus without astrogliosis. Among two studied drugs, spirofused oxindole has a more pronounced toxic effect on pyramidal neurons of the CA3 and CA4 fields of the hippocampus and astrocytic glia.

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