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Why NSAIDs damage the tissue that lines the gastrointestinal tract

Published on June 23, 2007 at 2:33 AM · No Comments

New versions of drugs like buffered aspirin and Vioxx could produce fewer harmful side effects thanks to research being done at Kansas State University's College of Veterinary Medicine.

K-State researchers are examining how nonsteroidal anti-inflammatory drugs, or NSAIDs, damage the tissue that lines the gastrointestinal tract. James Lillich, associate professor of clinical sciences, is leading the research. He said NSAIDs are some of the most commonly used prescription and over-the-counter drugs for relieving ailments from headaches to arthritis.

The research being done at K-State will benefit animals like horses that require NSAIDs for ailments related to their athletic activities.

"We treat horses the same way we treat humans, and horses get the same side effects," Lillich said.

NSAIDs work by blocking a type of enzyme called cyclooxygenase, or COX, which is needed for healthy cellular function. When tissue becomes inflamed, isoforms of the enzyme produce naturally occurring compounds called prostaglandins, which are responsible for the pain associated with inflammation. Although drugs inhibiting COX-2 reduce inflammation, their targets can spill over and also inhibit the gastrointestinal tract's ability to heal itself, leading to problems like ulcers.

"NSAIDs are doing more than just inhibiting COX," Lillich said. "You're going to have to deal with side effects with any drug."

In the intestines, healthy epithelial cells move toward damaged cells to repair wounds in a matter of minutes to hours.

"The epithelial cells in the GI tract are the barrier between your body and the outside world," Lillich said.

He said NSAIDs inhibit this migration. To find out why, Lillich took an intestinal cell line and exposed it to NSAIDs. He then used wounding assays to assess cell migration over a period of four hours.

"Wounding assays are a way we can look at, basically, the behavior of cells," Lillich said.

In the wounding assay, Lillich said cells are seeded on a base that resembles the substance they would normally anchor themselves to in the body. The cells lay themselves out as a flat, single layer, known as a monolayer. The cells are treated with NSAIDs, and then a portion of the monolayer is removed and examined to see the response over a short period of time.

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