Abstract

An antimicrobial drug of the fluoroquinolone group, ciprofloxacin, is widely used in Ukraine. However, some researchers have noted the probable hepatotoxicity of this drug with prolonged use or use of high doses of ciprofloxacin. The aim of this study was to compare the effects of carbon tetrachloride, as a classical model of hepatocyte injury, with the effects of ciprofloxacin.
 The aim of the study was to investigate the biochemical parameters of the liver when simulating toxic damage to hepatocytes with carbon tetrachloride or ciprofloxacin.
 Materials and methods. The study was carried out on isolated rat hepatocytes, in whose culture medium carbon tetrachloride or ciprofloxacin was added. After incubation in the supernatant and cell homogenate, the activities of marker enzymes of cytolysis were determined: ALT, AST, γ-GTP, LF, LDH, DC and MDA.
 Results. The introduction of ciprofloxacin into the culture of hepatocytes at a concentration of LC50 caused changes in biochemical parameters similar to those caused by carbon tetrachloride. Thus, an increase in ALT, AST, γ-GTP, LF, LDH, DC and MDA was observed when CCl4 or ciprofloxacin was added to the culture.
 Conclusion. Incubation of rat hepatocytes with carbon tetrachloride or ciprofloxacin caused an increase in the level of enzymes and lipid peroxidation products. These parameters are indicators of gross changes in cells, which are the result of impaired keto acid formation, impaired redox reactions, impaired glycogen production

Highlights

  • There is a steady increase in liver disease [1]

  • The experiment was performed on hepatocytes of male Wistar rats weighing 180– 220 g, in compliance with the requirements of the NUPh Bioethics Commission (Minutes No 7 of 20.10.2021) and complied with ARRIVE recommendations and was performed in accordance with the British Animal Act 1986, guided by EU Directive 2010/63 / EU on the protection of animals used for scientific purposes

  • The action of ciprofloxacin increases the rate of formation of lipid peroxidation (LPO) – diene conjugates (DC) and malonic dialdehyde (MDA) products in hepatocytes, which can cause cell damage [17, 18]

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Summary

Introduction

There is a steady increase in liver disease [1]. This is a consequence of the unfavourable environmental situation, increasing the impact of various chemical agents on humans and more [2]. In vitro models of liver pathology of various etiologies in pharmacological studies used tetrachloromethane CCl4 and ciprofloxacin. The first substance is hepatotoxin, which is traditionally used to simulate acute and chronic toxic and drug-induced liver damage [3,4,5]. Recent data suggest that it has a tendency to cause idiosyncratic drug-induced liver damage [6]. Liver enzymes have been shown to be impaired after ciprofloxacin in some patients and to improve clinical and biochemical parameters after discontinuation of this antibiotic [6]. An in vitro study of inhibition of human retinal pigment epithelial cell proliferation by ciprofloxacin showed that the concentration of ciprofloxacin, which inhibits growth by 50 % (IC50), is 14.1 μg/ml, and complete inhibition of cell growth was observed at 83 μg/ml [7]

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