Featured Research

from universities, journals, and other organizations

New insights into how antibiotics damage human cells suggest novel strategies for making long-term antibiotic use safer

Date:
July 3, 2013
Source:
Wyss Institute for Biologically Inspired Engineering at Harvard
Summary:
Scientists have discovered why long-term treatment with many common antibiotics can cause harmful side effects -- and they have uncovered two easy strategies that could help prevent these dangerous responses.

Antibiotics cause oxidative stress in cells, which leads to cellular damage. For example, in healthy cells (left), mitochondria, which are labeled yellow here, are long and highly branched. But in cells treated with the antibiotic ciprofloxacin (right), mitochondria are abnormally short and unbranched, and they do not function as well.
Credit: Sameer Kalghatgi and Catherine S. Spina

A team of scientists 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 -- and they have uncovered two easy strategies that could help prevent these dangerous responses. They reported the results in the July 3rd issue of Science Translational Medicine.

Related Articles


"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," said Jim Collins, Ph.D., who led the study. 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 team also treated mice with the same three antibiotics in mouse-sized doses similar to what patients receive in the clinic. Long-term treatment with each of the three antibiotics damaged the animal's lipids and caused levels of glutathione, one of the body's natural antioxidants, to fall -- another sign of oxidative stress.

To make a difference in the clinic, however, the scientists still needed a way to prevent antibiotic-induced oxidative stress -- or a way to remediate it as it was occurring. They found both. They were able to prevent oxidative stress by using a bacteriostatic antibiotic -- an antibiotic such as tetracycline that stops bacteria from multiplying but doesn't kill them. They could also ease oxidative stress by mopping up chemically reactive oxygen molecules with an FDA-approved antioxidant called N-acetylcysteine, or NAC, that's already used to help treat children with cystic fibrosis.

The new results come on the heels of two other recent breakthroughs on antibiotic treatment from Collins' group -- a report in Nature showing that viruses in the gut that infect bacteria harbor genes that confer antibiotic resistance, and another report in Science Translational Medicine showing that silver can boost the effectiveness of many widely used antibiotics.

"Jim and his team are moving at lightning speed toward unlocking the medical mysteries that stand in the way of safe and effective antibiotic treatment," said Don Ingber, M.D., Ph.D., Wyss Institute Founding Director. "Doctors have known for years that antibiotics occasionally cause serious side effects, and Jim's new findings offer not one but two exciting new strategies that could address this long-neglected public health problem."

Next, Collins plans more animal studies to work out the best ways to remediate oxidative stress. But since both bacteriostatic antibiotics and NAC are already FDA-approved, doctors might be using this strategy soon.

"We're interested in seeing if this could be moved toward the clinic," Collins said.


Story Source:

The above story is based on materials provided by Wyss Institute for Biologically Inspired Engineering at Harvard. Note: Materials may be edited for content and length.


Journal Reference:

  1. Sameer Kalghatgi, Catherine S. Spina, James C. Costello, Marc Liesa, J. Ruben Morones-Ramirez, Shimyn Slomovic, Anthony Molina, Orian S. Shirihai, and James J. Collins. Bactericidal Antibiotics Induce Mitochondrial Dysfunction and Oxidative Damage in Mammalian Cells. Science Translational Medicine, 3 July 2013 DOI: 10.1126/scitranslmed.3006055

Cite This Page:

Wyss Institute for Biologically Inspired Engineering at Harvard. "New insights into how antibiotics damage human cells suggest novel strategies for making long-term antibiotic use safer." ScienceDaily. ScienceDaily, 3 July 2013. <www.sciencedaily.com/releases/2013/07/130703160623.htm>.
Wyss Institute for Biologically Inspired Engineering at Harvard. (2013, July 3). New insights into how antibiotics damage human cells suggest novel strategies for making long-term antibiotic use safer. ScienceDaily. Retrieved December 20, 2014 from www.sciencedaily.com/releases/2013/07/130703160623.htm
Wyss Institute for Biologically Inspired Engineering at Harvard. "New insights into how antibiotics damage human cells suggest novel strategies for making long-term antibiotic use safer." ScienceDaily. www.sciencedaily.com/releases/2013/07/130703160623.htm (accessed December 20, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, December 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
The Best Protein-Filled Foods to Energize You for the New Year

The Best Protein-Filled Foods to Energize You for the New Year

Buzz60 (Dec. 19, 2014) The new year is coming and nothing will energize you more for 2015 than protein-filled foods. Fitness and nutrition expert John Basedow (@JohnBasedow) gives his favorite high protein foods that will help you build muscle, lose fat and have endless energy. Video provided by Buzz60
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins