INVESTIGATING EFFECTS OF 7,8-DISUBSTITUTED DERIVATIVE OF THEOPHYLLINE (BENOPHYLLINE) ON FREE-RADICAL OXIDATION IN RENAL INJURY OF RATS
Authors: Matviiychuk A. P. , Yeremenko R. F. , Matviiychuk A. V. , Taran A. V. , Hladchenko O. M. 
Published: April 2020

This article highlights the pharmacological study of new 7,8-disubstituted derivative of theophylline, the substance conditionally named benophylline. Based on the literature data and previous studies of compounds of this class, it has been concluded that studying the effect of benophylline on the pro-antioxidant system under simulated pathologies is of great interest and importance.

 The study of antihypoxic action of 7,8-disubstituted theophylline in rats was carried out under modelled normobaric hypoxia with hypercapnia (in an enclosed space). It has been found out the application of 7-n-methylbenzyl-8-substituted polyphosphonates increases the longevity of rats in the conditions described above that evidences the improvement of metabolic processes in mitochondrial respiratory chain.

Based on the results of screening studies, we selected 7,8-disubstituted derivative of theophylline (benophylline) as a leading substance for further investigation. The purpose of the study was to evaluate the efficacy of benophylline for the pharmacological correction of free radical processes in experimental renal damage in rats based on the evaluation of the expression of lipid peroxidation and antioxidant protection.

Materials and methods: blood serum, homogenate and rat kidney tissues were the study materials. The study of the protective effect of benophylline on the functional state of the kidneys was investigated on experimental model of acute renal injury by introducing 50% water solution of glycerol (myoglobin nephropathy). Pathogenesis of this model was described in the methodological recommendations by C. Yu. Shtrygol, V. M. Lysovoi, I. A. Zupanetz et al. in «Methods of experimental modeling of kidney damage for pharmacological research». The content of TBK-R was determined spectrophotometrically by reaction with thiobarbituric acid.

Glutathione recovered activity was determined spectrophotometrically in reaction with Elman's reagent using the method of Beutler E. D. et al. The catalase activity was assessed by the method of M.A. Koroluk et al. The influence of benophylline on the morphological state of the renal parenchyma was assessed on the modeled myoglobin nephropathy. The activity of gamma-glutamyltranspeptidase in serum was evaluated photometrically using a reagent test kit (“Filisit”). Statistical processing of the results was performed using the STATISTICA 8.0 software package, with the mean value, standard error of the mean confidence interval (p≤0.05). The microscopic study of microproducts was performed under the Granum microscope. Micrographs were taken with a Granum DMC 310 digital camera. The images were processed on a Pentium 2.4 GHz computer using Toup View software.

Research results: Under the influence of benophylline, the processes of LPO and AOP became normalized, the expressiveness of degradation of the nephrocytes decreased, the microscopic picture of renal excretion in all rats got normalized. At the same time, 62.5% of the rats had the morphological condition of kidneys close to the intact control, and 37.5% of the animals were noticed to demonstrate a significant decrease in the dyscirculatory abnormalities, inflammatory manifestations and signs of nephrocyte regeneration.

Conclusions: The ability of benophylline to inhibit the processes of free radical oxidation and to enhance antioxidant protection has been found out. The study has shown benophylline enhances regenerative effect kidney tissues.