Analysis of the toxic effects of fluoroquinolones in laboratory rabbit models

Introduction. Fluoroquinolones are antibacterials for which the development of cardiotoxicity, hepatotoxicity, nephrotoxicity and connective tissue damage has been noted. The likely mechanism for the development of these reactions is magnesium metabolism disorder. An available method to detect fluoroquinolones toxicity in animal experiments is a blood biochemical test.

The aim of the work was to identify the biochemical signs of the toxic effects of fluoroquinolones in laboratory rabbit models.

Materials and methods. Twenty male rabbits randomised into three groups were included in the study: 6 control animals; 7 rabbits treated with ciprofloxacin 150 mg/kg 14 days; 7 rabbits treated with levofloxacin 150 mg/kg 14 days. Serum levels of albumin, alanine aminotransferase (liver damage marker), creatinine (nephrotoxicity marker), creatine kinase MB (cardiotoxicity marker), matrix metalloproteinase 9 (connective tissue damage marker), serum and plasma magnesium content were studied in this work. Data are presented as mean (standard deviation).

Results. Serum levels of albumin, alanine aminotransferase and creatinine did not change during the experiment. Rabbits treated with levofloxacin had 2.0–2.5 times lower values of CF creatine kinase activity than control animals. There was double increase of serum concentration of matrix metalloproteinase 9 in ciprofloxacin group in comparison with control (70,17 (20,88) and 38,10 (16,04) ng/ ml, p = 0,019). Magnesium content was unchanged with both fluoroquinolones.

Discussion. The absence of signs of hepatotoxicity and nephrotoxicity is consistent with their low frequency of detection in clinical and experimental studies. A decrease in the activity of creatine kinase MB in animals treated with levofloxacin has not been described in the literature. An increase in the concentration of metalloproteinase 9 is evidence of destruction of connective tissue structures. The absence of changes in serum and plasma concentrations of magnesium is explained by the functioning of the systems maintaining the constancy of its content in blood.

Conclusion. No biochemical evidence of hepato-, nephro- and cardiotoxic effects of ciprofloxacin and levofloxacin at the doses of 150 mg/kg for 14 days was shown in rabbits; no magnesium metabolism disorders were shown, and the ability of ciprofloxacin to increase the serum content of matrix metalloproteinase type 9 was demonstrated. The proposed model can be used to investigate ways to prevent the toxic effects of fluoroquinolones on connective tissue structures.

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