Featured Research

from universities, journals, and other organizations

New anti-inflammatory drugs pinch off reactive oxygen species at the source

Date:
June 21, 2012
Source:
Emory University
Summary:
Scientists have identified a new type of anti-inflammatory compound that may be useful in treating a wide range of conditions, including neurodegenerative and autoimmune diseases. These compounds inhibit the enzyme Nox2, part of a family of enzymes responsible for producing reactive oxygen species.

Scientists at Emory University School of Medicine have identified a new type of anti-inflammatory compound that may be useful in treating a wide range of conditions, including neurodegenerative and autoimmune diseases. These compounds inhibit the enzyme Nox2, part of a family of enzymes responsible for producing reactive oxygen species (ROS).

The results were published in the journal Chemistry & Biology.

"Nox2 inhibitors could be valuable with many conditions where inflammation plays a role," says senior author David Lambeth, MD, PhD, professor of pathology and laboratory medicine at Emory University School of Medicine.

ROS and the Nox enzymes play vital roles in the immune and cardiovascular systems, but too much ROS leads to oxidative stress, linked with tissue damage and conditions such as stroke, heart failure and neurodegenerative diseases.

Antioxidants are supposed to absorb ROS, but many clinical studies examining antioxidants' benefits have been disappointing. Compounds that inhibit the Nox enzymes would stop ROS production at the source, rather than mop them up like antioxidants do.

"We are taking a completely different approach," says first author Susan Smith, PhD, Emory research assistant professor of pathology and laboratory medicine. "If a burst pipe is gushing water all over the basement, the first thing you need is a wrench to stop the water from flowing, instead of a mop."

The Nox inhibitors that were already available to researchers are not specific enough for one enzyme over another. Smith collaborated with research scientist Jaeki Min and colleagues at the Emory Chemical Biology Discovery Center and Emory Institute for Drug Development to screen for compounds that inhibit Nox2. In particular, they searched for compounds that interfere with assembly of the Nox2 enzyme rather than targeting the catalytic site.

The screen for compounds that inhibit Nox2 led to the identification of ebselen, a drug that has been tested previously in clinical trials in acute stroke and more recently, hearing loss. Previous researchers had thought that ebselen acted by another mechanism. Smith and Lambeth say their results do not conflict with earlier reports, and ebselen may have several modes of action depending on the concentration. Ebselen inhibited the Nox2 enzyme and to a lesser extent, Nox1, but not other Nox enzymes.

A side effect of Nox2 inhibition could be impairment of immune responses to bacteria and fungi, Lambeth says. One of Nox2's main functions in immune cells is to produce a toxic burst of ROS for killing bacteria and fungi.

People with an inherited deficiency in Nox2 develop chronic granulomatous disease (CGD), and are unable to fight off common infections. However, short-term or incomplete inhibition could have therapeutic effects without disabling antibacterial activity. CGD carriers who have reduced but residual Nox2 activity do not display symptoms.

Lambeth says the identification of ebselen is a starting point for refining drugs that target Nox2 and other Nox enzymes.

"This is just the tip of the iceberg," he says. "It's a good sign that ebselen is relatively non-toxic. Through medicinal chemistry, it should be possible to generate even more potent inhibitors, which could be candidates for drug development."


Story Source:

The above story is based on materials provided by Emory University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Susan M.E. Smith, Jaeki Min, Thota Ganesh, Becky Diebold, Tsukasa Kawahara, Yerun Zhu, James McCoy, Aiming Sun, James P. Snyder, Haian Fu et al. Ebselen and Congeners Inhibit NADPH Oxidase 2-Dependent Superoxide Generation by Interrupting the Binding of Regulatory Subunits. Chemistry & Biology, 22 June 2012 DOI: 10.1016/j.chembiol.2012.04.015

Cite This Page:

Emory University. "New anti-inflammatory drugs pinch off reactive oxygen species at the source." ScienceDaily. ScienceDaily, 21 June 2012. <www.sciencedaily.com/releases/2012/06/120621130712.htm>.
Emory University. (2012, June 21). New anti-inflammatory drugs pinch off reactive oxygen species at the source. ScienceDaily. Retrieved October 22, 2014 from www.sciencedaily.com/releases/2012/06/120621130712.htm
Emory University. "New anti-inflammatory drugs pinch off reactive oxygen species at the source." ScienceDaily. www.sciencedaily.com/releases/2012/06/120621130712.htm (accessed October 22, 2014).

Share This



More Health & Medicine News

Wednesday, October 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Working Mother (Oct. 22, 2014) Is your child ready? Video provided by Working Mother
Powered by NewsLook.com
U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

Newsy (Oct. 22, 2014) Now that the U.S. is restricting travel from West Africa, some are dropping questions about a travel ban and instead asking about visa bans. Video provided by Newsy
Powered by NewsLook.com
US to Track Everyone Coming from Ebola Nations

US to Track Everyone Coming from Ebola Nations

AP (Oct. 22, 2014) Stepping up their vigilance against Ebola, federal authorities said Wednesday that everyone traveling into the US from Ebola-stricken nations will be monitored for symptoms for 21 days. (Oct. 22) Video provided by AP
Powered by NewsLook.com
Doctors Help Paralysed Man Walk Again, Patient in Disbelief

Doctors Help Paralysed Man Walk Again, Patient in Disbelief

AFP (Oct. 22, 2014) Polish doctors describe how they helped a paralysed man walk again, with the patient in disbelief at the return of sensation to his legs. Duration: 1:04 Video provided by AFP
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