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Some antibiotics can have undesired effects on the metabolism, causing severe symptoms. The group of fluoroquinolones with its most famous member ciprofloxacin is such a case: Fluoroquinolones are some of the most frequently used broad-spectrum antibacterial antibiotics, and usually prescribed for respiratory, urinary or ear infections.
Some patients using fluoroquinolones develop severe tendon rupture, permanent nerve damage or depression. A study carried out at the University of Eastern Finland investigated the effect of ciprofloxacin on mitochondria, the important cell organelles in our body that produce the energy for cellular function.
Mitochondria possess their small circular genome, which requires topoisomerase enzymes for its maintenance. Topoisomerases regulate the topology of DNA and untangle for instance knots and overwound stretches of a genome by cutting and reconnecting the DNA sequence. While fluoroquinolones are designed to inhibit the bacterial topoisomerase gyrase, which leads to the death of the bacterium, they also inhibit the topoisomerase 2 of human cells.
Topoisomerase 2 is especially important in the replication of the mitochondrial genome, as it regulates the winding of this small DNA molecule by removing positive twists. Ciprofloxacin stopped this normal maintenance and transcription of mitochondrial DNA by changing mtDNA topology, causing impaired mitochondrial energy production and blocking cellular growth and differentiation. This dramatic impact on mitochondrial DNA is the cause for most negative side effects experienced by patients.