The impact of a binary catalyst system «tereftal + ascorbic acid» on the central nervous system

Abstract

Introduction. Neurotoxicity is one of the specific systemic complications of anticancer chemotherapy. Detection in experimental animals complications of psychotropic or neurotropic action of the new drug is one of the most difficult challenges of preclinical toxicology. Preclinical toxicological study of the effect of a binary catalyst system «tereftal + ascorbic acid» on the central nervous system (CNS). Objective. The prediction of toxic effects of binary catalytic system in clinical application in patients. Materials and methods. The study was conducted on 300 male mice hybrids (CBA х C57 Bl/6J) F1. Have terephtal - russian drug. A binary catalyst system was injected intravenously once at close to the maximum tolerated dose - 50 mg/kg tereftal + 110 mg/kg ascorbic acid and in therapeutic dose - 20 mg/kg tereftal + 44 mg/kg ascorbic acid. The obtained data were compared with a control animal treated with saline solution and with the data of animals treated with one tereftal and one ascorbic acid in equivalent doses. To assess neurotoxicity tests used standard neuropharmacological screening. An assessment of emotional status, muscle tone were undertaken. Behavior was evaluated in the tests «open field» and «aggression». We evaluated the response to pain stimulation, the change in rectal body temperature. Higher integrative brain functions were investigated on the model of the conditioned reflex of passive avoidance. Estimated effect on convulsive readiness of the CNS. Results. The catalytic system changed the general condition of the animals. This was manifested, on the one hand, in the suppression of their overall activity (sluggishness, inactivity until weakness, muscle relaxation, the lowering side, the slowing of breathing), the other - to increase their excitability (when in group, some animals adopted a characteristic aggressive stands, in some cases seizures). These animals were observed exophthalmos, the appearance of the position «frog», posture «praying mouse», the desire to hide. The inhibitory effect of the catalytic system was dose-dependent. Observed inhibition of various forms of behavior, emotional status, decrease in body temperature and pain sensitivity, in the test for aggression - reducing the number of fights, in open field test - locomotor activity suppression. Spontaneous seizures in the provocation corazol binary catalytic system was not strengthened. Conclusion. The obtained data allow to predict toxic effects from the CNS during clinical use of binary catalytic system «tereftal + ascorbic acid»: total confusion, lethargy, physical inactivity, decrease in body temperature, increased anxiety and aggression and, in very rare cases, the occurrence of seizures.