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How Fluoroquinolones Work

 

Antibiotics kill bacteria by disrupting one of the processes they need to survive e.g. by damaging bacterial cell walls or preventing them from turning glucose into energy.

 

Quinolones (also called Fluoroquinolones) work by targeting particular enzymes called topoisomerase II and topoisomerase IV which the bacterial cell needs to replicate its DNA. If the DNA is damaged the cell can't replicate itself, and ultimately the bacterial infection is defeated.

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When quinolones were being developed 30 or so years ago, it was firmly believed that only plants and bacteria have these enzymes. However, a paper was published in 1996 which demonstrated that mammalian cells do have this particular enzyme in their mitochondria – and that ciprofloxacin also damaged these mammalian cells.

Delayed cytotoxicity and cleavage of
mitochondrial DNA in ciprofloxacin-treated mammalian cells. Lawrence, J. W. et al (1996)

 

Fluoroquinolones were hailed as the miracle-drugs that meant we could at last defeat anthrax and other super-bugs. The small matter of possible damage to nearly every human cell was conveniently left unnoticed and is not acknowledged by many doctors to this day.  There were other problems with toxicity, and many early versions of these antibiotics had to be withdrawn because of deaths and serious adverse reactions.

 

Today the later versions, such as ciprofloxacin and levofloxacin, are consistently growing in popularity and millions of prescriptions are written for them every year. Although they are designated  '3rd line defence' antibiotics, and are supposed to be reserved for only the most serious bacterial infections such as E.Coli and sepsis, the reality is that they are routinely given for sinus, prostate and UTI problems, along with many “just-in-case” scenarios.

Mitochondria: why they are important

 

Mitochondria are organelles (tiny organisms) found in both animal and plant cells, and probably originate from when everything was evolving together in the primeval soup. The number of mitochondria within a cell varies, depending on the type and function of that cell. Mature red blood cells, for instance, do not contain any mitochondria. This leaves room for the millions of haemoglobin molecules needed to transport oxygen throughout the body. Muscle cells, on the other hand, contain many thousands of mitochondria in order to provide the energy required for muscle activity; a heart muscle cell has around 5000. Mitochondria are not so abundant in fat cells, while liver cells are estimated to have about 2000.

http://biology.about.com/od/cellanatomy/ss/mitochondria.htm

So each of our trillions of cells has a nucleus with its own DNA, and then the majority of our cells also contain thousands of mitochondria, which have their own DNA (known as mtDNA). Mitochondria are literally the powerhouses of our bodies because they perform the vital task of generating ATP (adenosine triphosphate), the molecule that each cell uses for its energy needs. Mitochondrial damage, which can be caused by various factors including quinolone antibiotics, is linked to symptoms such as fatigue, muscle pain, abdominal pain, shortness of breath, collagen vascular disease, chronic fatigue syndrome, fibromyalgia, or psychosomatic illness.

Mitochondrial cytopathy in adults: what we know so far. B. H. Cohen & D. R. Gold, 2001.

Collagen: why it's important

Collagen is the most abundant protein in the human body and is found in the bones, muscles, skin and tendons, where it forms a scaffold to provide strength and structure – it literally holds the whole body together.

There are at least 16 different types of collagen, but 80-90% of collagens in the body belong to types I, II and III. Type I collagen fibrils are particularly tensile, and are stronger than steel, gram for gram. These are found in tendons, skin, artery walls, cornea, the covering surrounding muscle fibres, fibrocartilage (e.g. the discs between the vertebrae), and the organic part of bones and teeth. Type II is found in the vitreous humour of the eye, and type III is found in the artery walls, skin, intestines and the uterus.

Collagen plays numerous important roles in health, and thus the breakdown and depletion of the body's natural collagen is associated with a number of health problems. Mitochondrial damage caused by fluoroquinolones can affect collagen all over the body, creating many diverse symptoms such as eye problems and Achilles tendon pain. Fluoroquinolones prevent energy synthesis, not only impairing the way the cells replicate themselves but also accelerating cell breakdown. Simply put, all collagen cells are at risk of being destroyed, while regrowth is impaired with essential crosslinks and fibres not forming. This results in structural weakness and instability. Because of impaired regrowth, the biggest problem for sufferers is that the tendons are very likely to be further damaged by normal sports-injury therapy. Many sufferers have discovered to their cost that physiotherapy treatment, or even just trying to exercise, causes the damage to worsen.

Find out more:  Electron microscopy has confirmed that fluoroquinolones can cause the tendon cells to die prematurely (4/5/6).

4. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921747/

The Risk of Fluoroquinolone-induced Tendinopathy and Tendon Rupture.

G.K.Kim. 2005

5. http://www.ncbi.nlm.nih.gov/pubmed/26205818

Nonantibiotic Effects of Fluoroquinolones in Mammalian Cells.  Badal et al.  2015

6. https://www.ncbi.nlm.nih.gov/pubmed/15890441

Sendzik J, Shakibaei M, Schafer-Korting M, Stahlmann R. Fluoroquinolones cause changes in extracellular matrix, signaling proteins, metalloproteinases and caspase-3 in cultured human tendon cells. Toxicology. 2005; 212:24-36.

Other important damage

Fluoroquinolones affect how each of our cells work in many other ways too. A paper which describes exactly what happens was published in October 2017, but is quite hard to understand so we took the liberty of writing our own version. To read it, click on Academic Paper 2017 in the website main menu.

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