The role of glia in the mechanisms of neural protection of the fixed combination of ipidacrine hydrochloride / phenibut on the background of drug-induced liver injury

Abstract

Topicality. The main disadvantage of the first-line anti-TB drugs isoniazid and rifampicin is their ability to cause drug-induced liver injury. At the same time, in addition to hepatotoxic, in 12-24 % of cases are neurological disorders. The consequence of these processes is a disturbance of synaptic plasticity, learning processes and memory. In addition, significant factor in the development of neurological disorders may be an imbalance of intestinal microflora. One of the possible options at eliminating or attenuating the manifestations of cognitive deficiency in various pathological conditions is the appointment of drugs with neuroprotective properties. However, even today their effectiveness studied not enough for central nervous system dysfunctions arising from prolonged anti-TB therapy. Therefore, we can assume that neurological disorders can be due to a complex of interrelated factors.Aim. To determine the morphometric and ultrastructural features of neurons and glial cells, as well as the levels of glial fibrillary acid protein (GFAB) in the hippocampus of rats under long-term administration of isoniazid and rifampicin during experimental therapy with a fixed combination of ipidacrine hydrochloride/phenibut.Materials and methods. Studies were conducted on three groups of white Wistar male rats with drug-induced hepatitis, reproduced by intragastric administration of isoniazid and rifampicin for 28 days. In the last 14 days of the intragastric experiment, rats of the research group were administered ipidacrine hydrochloride/phenibut (1/60 mg/kg). The content of cytosolic GFAP in the hippocampus was determined by competitive enzyme-linked immunosorbent assay. Semi-thin sections of CA1 sections of the rat hippocampus were analyzed, Image J. analysis program used. The ultrastructural characteristics were studied, PEM-100-01 transmission electron microscope used (Selmi, Ukraine).Results and discussion. Under the experimental pharmacotherapy the specific number of degeneratively altered neurons was significantly lower than in the controlled animals. At the same time, astrocytes were characterized by significantly less edema of the cytoplasm and adaptive-compensatory changes in mitochondria, and the content of cytoplasmic GFAP was 44.2 % (P = 0.0065) lower than the group of animals with hepatitis.Conclusions. Course administration of ipidacrine and phenibut reduces the severity of neurodegeneration appearance, improves the state of astroglia in the hippocampus, and it also reduces the cytoplasmic levels of glial acidic fibrillary protein in animals with drug-induced liver injury.