Ciprofloxacin toxicity on isolated heart mitochondria a justification for their cardiotoxic adverse effect

Ciprofloxacin is a broad_spectrum antibiotic that is commonly administered for treatment of various bacterial infections including joint and bone infections, urinary tract infections and respiratory infections. Ciprofloxacin has different adverse effects and also impacts on heart function. The mechanism of cytotoxicity action of ciprofloxacin in cardioyoxicity is not fully understood; therefore, we decided to investigate the effects of ciprofloxacin in isolated rat heart mitochondria. The importance of mitochondrial study in the cytotoxicity is very high. Mitochondria is one of the most important intracellular organelles that is the main source of production of active oxygen species in the cell. The mitochondria are actually a cellular respiratory organelle that, during the oxidative phosphorylation process, generates most of the ATP required by the cell, and on the other hand, active oxygen species are produced as a byproduct during this process. Methods: All of the materials were purchased from Sigma-Aldrich Co. (Taufkirchen, Germany). In addition, Chemicals were of the highest commercial grade available. The ciprofioxacin on mitochondrial related parameters including succinate dehydrogenase activity, the activity of mitochondrial complex II (succinate dehydrogenase) was assayed through the measurement of MTT reduction and absorbance at 570 nm was measured with an ELISA reader. Isolated mitochondria were incubated in media culture of DMEM. a sample was taken and 2,7dichlorofluorescin diacetate (DCFH-DA) was measured by Spectrofluorimetry The mitochondrial uptake of the cationic fluorescent dye, rhodamine 123, was used for determination of mitochondrial membrane potential (MMP) was measured by flowcytometry. We isolated mitochondria from control groups and three mitochondrial toxicity parameters including collapse of mitochondrial membranc potential mitochondrial swelling. Reactive oxygen radical formation and finally release of cytochrome c, which is the start point of cell death signalingwher, then investigated. Results: Our results demonstrated that ciprofloxacin induced reactive oxygen species formation, mitochondrial swelling and mitochondrial membrane permeabilization and cytochrome c release in cardiomyocyte mitochondria. These findings suggested that the toxicity of heart mitochondria is a starting point for cardiotoxic effects.

Keywords:

Ciprofloxacin , isolated mitochondria , reactive oxygen species (ROS) , mitochondrial membrane potential (MMP) , cytochrome c