Newly discovered NSAID mechanism may explain diverse clinical effects

Newly discovered NSAID mechanism may explain diverse clinical effects

Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and aspirin are widely used to treat pain and inflammation. But even at similar doses, NSAIDs can have unexpected and unexplained effects on many diseases, including heart disease and cancer.

Now, a new study led by Yale University has revealed a previously unknown process by which certain NSAIDs affect the body. This finding may explain why similar NSAIDs produce a range of clinical outcomes and could clarify how the drugs may be used in the future.

The study was published May 23 in the journal immunity.

Until now, it was believed that the anti-inflammatory effects of NSAIDs arise only through the inhibition of certain enzymes. But this mechanism does not take into account many clinical outcomes that differ for different family of drugs. For example, some NSAIDs prevent heart disease while others cause it, some NSAIDs have been linked to a lower incidence of colorectal cancer, and NSAIDs can have a wide range of effects on asthma.

Now, using cell cultures and mice, Yale researchers have discovered a distinct mechanism by which a subset of NSAIDs reduce inflammation. This mechanism may help explain some of these strange effects.

Research has shown that only some NSAIDs — including indomethacin, which is used to treat arthritis and gout, and ibuprofen — also activate a protein called nuclear erythroid-related factor 2, or NRF2, which, among many actions, stimulates anti-inflammatory processes. inflammatory in the body.

“It is interesting and exciting that NSAIDs have a different mode of action than was previously known,” said Anna Eisenstein, M.D., a professor at Yale University School of Medicine and the study’s lead author. “And because people frequently use NSAIDs, it is important to know what they are doing in the body.”

The research team cannot be certain that the unexpected effects of NSAIDs are caused by NRF2 – which will require further research. “But I think these results are suggestive,” Eisenstein said.

Eisenstein is now looking at some of the dermatological effects of the drugs — which cause rashes, exacerbate hives and worsen allergies — and whether they are mediated by NRF2.

The researchers note that this finding still needs confirmation in humans. But if so, the findings may have implications for how inflammation is treated and how NSAIDs are used.

For example, several clinical trials are evaluating whether drugs that activate NRF2 are effective in treating inflammatory diseases such as Alzheimer’s disease, asthma, and various types of cancer. This research could inform the potential and limitations of these drugs. In addition, NSAIDs may be prescribed more effectively in the future, with NRF2-activated NSAIDs and non-NRF2-activated NSAIDs applied to the diseases they are likely to treat.

Eisenstein said the findings may also point to entirely new applications for NSAIDs.

NRF2 controls a large number of genes involved in a wide range of processes, including metabolism, immune response, and inflammation. The protein has been implicated in aging, longevity, and reduced cellular stress.

“This NRF2 very much suggests that NSAIDs may have other effects, both beneficial and adverse, that we haven’t looked at yet,” Eisenstein said.

reference: Eisenstein A, Hilliard BK, Bob SD, et al. Activation of the transcription factor NRF2 mediates the anti-inflammatory properties of a subset of over-the-counter NSAIDs. immunity. 2022; 0 (0). doi: 10.1016/j.immuni.2022.04.015

This article has been republished from the following articles. Note: The article may have been modified for length and content. For more information, please contact the mentioned source.

2022-05-24 09:27:24

Leave a Comment

Your email address will not be published.