Scientists at the Wyss Institute for Biologically Inspired Engineering at Harvard University have gained new insight into the dangers associated with long-term antibiotic usage. The scientists, led by Jim Collins, Ph.D., have discovered the cause behind hazardous side effects resulting from long-term usage of antibiotic drugs and have proposed two solutions to prevent and reduce these negative effects.
Doctors have been prescribing antibiotics under the general assumption that the drugs harm only bacterial and not human cells. Contrary to this belief, adverse effects such as tendonitis, hearing loss, diarrhea, and kidney dysfunction have all been reported with long-term use of antibiotics. The research team at the Wyss Institute found that these side effects occur as a result of human cells suffering oxidative stress, causing damage to DNA, proteins, and lipids. Collins proposed that the oxidative stress arose from production of chemically reactive oxygen molecules, those oxygen molecules being responsible for the damage occurring in the cells.
The research team found that Collins’ proposal was the exact mechanism of action antibiotics used to kill bacterial cells; researchers Sameer Kalghatgi, Ph.D., and Catherine S. Spina, M.D./Ph.D. candidate at Boston University, continued this research to investigate whether oxidative stress was also affecting mitochondria, which are bacteria-like organelles responsible for energy production in human cells. Kalghatgi and Spina tested clinical levels of three different antibiotics (Ciprofloxacin, Ampicillin, and Kanamycin) to carry out this investigation. They found that after six hours the treatments were safe, but extended use of the drugs caused mitochondrial malfunction and evidence of damaged DNA, proteins, and lipids of cultured human cells. They repeated this experiment on mice subjects and found similar results. The damage they observed resulting from long-term use of the antibiotics is characteristic of oxidative stress, thus supporting their initial inferences.
The Wyss Institute research team, using their novel information regarding antibiotic side effects, proposed both a solution to prevent the occurrence of oxidative stress in the cells and also a way to lower that stress if already induced. Prevention of oxidative stress, they proposed, could be accomplished by using bacteriostatic antibiotics, tetracyclines for example, in order to prevent bacterial replication without actually killing the bacteria. If the cell is already experiencing oxidative stress, the use of FDA-approved N-acetylcysteine (NAC), currently used for treatment of cystic fibrosis, can reduce the amount of reactive oxygen molecules present in the cell, reducing the stress and likewise the negative effects it can have.
The novel insights and discoveries made by Collins and his research team at the Wyss Institute are exciting for the future of addressing this previously neglected health problem. One major message to be taken away from these findings is to use antibiotics sparingly and only in cases of serious bacterial infections.