Gut throws cells overboard when chemical insults build up

Admin on 01 / 09 / 2019 under Open access

Source: Duke University

 

Summary: Researchers were testing more than 20 non-steroidal anti-inflammatory drugs (NSAID) in an attempt to make the zebrafish a new model for studying chemical injury in the gut. What they found was unexpected: the gut was systematically sloughing off epithelial cells as a defense mechanism against a molecule that inhibited the MDR efflux pumps that protect cells.

A team of Duke researchers has discovered that cells lining the gut of zebrafish -- and probably humans too -- have a remarkable defense mechanism when faced with certain kinds of toxins: they hit the eject button.

"The gut has the challenging job of handling all the chemicals that we consume or produce, and some of those chemicals can be damaging. So the gut has evolved many interesting ways to defend against damage," said Ted Espenschied, a Duke graduate student who led the effort as part of his dissertation research.

 

The Duke team was testing more than 20 non-steroidal anti-inflammatory drugs (NSAID) in an attempt to make the zebrafish a new model for studying chemical injury in the gut. The fish are cheap to maintain, easy to breed, and most importantly, translucent for the early part of their lives, Rawls said. It's also easy to administer chemical exposures and measure their environmental conditions via the tank water.

 

The researchers found something unexpected. "It's often the case that drugs have multiple off-target effects," said John Rawls, an associate professor of molecular genetics and microbiology and director of the Duke Microbiome Center.

 

But only one of the drugs they tested seemed to create any measurable differences in the fish, an old NSAID called Glafenine. It had been an over-the-counter oral painkiller used in Europe and the Middle East for three decades, but was taken off the market after being linked to kidney and liver damage.