The team at the Wyss Institute for Biologically Inspired Engineering at Harvard University has discovered why long-term treatment with many common antibiotics can cause harmful side effects.
"Clinical levels of antibiotics can cause oxidative stress that can lead to damage to DNA, proteins and lipids in human cells, but this effect can be alleviated by antioxidants," Jim Collins, Ph.D., who led the study, said.
Collins, a pioneer of synthetic biology and Core Faculty member at the Wyss Institute, is also the William F. Warren Distinguished Professor at Boston University, where he leads the Center of Synthetic Biology.
Doctors often prescribe antibiotics freely, thinking that they harm bacteria while leaving human tissue unscathed.
But over the years reports have piled up about the occasional side effects of various antibiotics, including tendonitis, inner-ear problems and hearing loss, diarrhea, impaired kidney function, and other problems.
Collins suspected these side effects occurred when antibiotics triggered oxidative stress - a condition in which cells produce chemically reactive oxygen molecules that damage the bacteria's DNA and enzymes, as well as the membrane that encloses the cell.
Collins' team had already discovered that antibiotics that kill bacteria do so by triggering oxidative stress in the bacteria.
They wondered whether antibiotics caused side effects by triggering oxidative stress in the mitochondria, a bacterium-like organelle that supplies human cells with energy.
Sameer Kalghatgi, Ph.D., a former postdoctoral fellow in Collins' laboratory who is now Senior Plasma Scientist at EP Technologies in Akron, Ohio, and Catherine S. Spina, a M.D./Ph.D. candidate at Boston University and researcher at the Wyss Institute, first tested whether clinical levels of three antibiotics -- ciprofloxacin, ampicillin, kanamycin -- each cause oxidative stress in cultured human cells.
They found that all of these drugs were safe after six hours of treatment, but longer-term treatment of about four days caused the mitochondria to malfunction.
Kalghatgi and Spina then did a series of biochemical tests, which showed that the same three antibiotics damaged the DNA, proteins and lipids of cultured human cells - exactly what one would expect from oxidative stress.
The results mean that "doctors should only prescribe antibiotics when they're called for, and patients should only ask for antibiotics when they have a serious bacterial infection," Collins said.
The research is published in the journal Science Translational Medicine.
--ANI (Posted on 04-07-2013)