Unexpected side effects of common painkillers found in study

Even at comparable doses, popular painkillers can have unexpected and unexplained effects on a variety of illnesses, including heart disease and cancer, according to a recent study.

The research findings were published in the journal ‘Immunity.’ A new Yale-led study has discovered a previously unknown mechanism through which some NSAIDs influence the body. The discovery might explain why comparable NSAIDs create such a wide variety of clinical outcomes, as well as guide future medication usage.

Until today, it was thought that NSAIDs’ anti-inflammatory effects were entirely due to the inhibition of certain enzymes. However, many clinical outcomes that differ between medication families are not explained by this mechanism. For example, some NSAIDs protect cardiac disease while others cause it; certain NSAIDs have been associated to a lower risk of colorectal cancer; and different NSAIDs can have a variety of asthmatic effects.

Yale researchers have discovered a different method through which a subset of NSAIDs decrease inflammation using cell cultures and animals. And that process might explain some of the strange outcomes we’ve seen.

Only a few NSAIDs, such as indomethacin (used to treat arthritis and gout) and ibuprofen, were shown to activate a protein called nuclear factor erythroid 2-related factor 2, or NRF2, which, among other things, stimulates anti-inflammatory mechanisms in the body.

“It’s interesting and exciting that NSAIDs have a different mode of action than what was known previously,” said Anna Eisenstein, an instructor at the Yale School of Medicine and lead author of the study. “And because people use NSAIDs so frequently, it’s important we know what they’re doing in the body.”

The research team can’t say for sure that NSAIDs’ unexpected effects are due to NRF2 — that will require more research. “But I think these findings are suggestive of that,” Eisenstein said.

Eisenstein is currently investigating if NRF2 is involved in some of the medications’ dermatological effects, such as producing rashes, aggravating hives, and increasing allergies.

The researchers point out that this discovery has to be validated in people. However, if this is the case, the findings may have ramifications for how inflammation is managed and how NSAIDs are administered.

Also Read: Popping Painkillers Regularly can cause Hearing Loss

Several clinical trials, for example, are exploring whether NRF2-activating medications are useful in treating inflammatory disorders such as Alzheimer’s disease, asthma, and malignancies; this research might help determine the potential and limitations of those treatments. Furthermore, NSAIDs may be prescribed more successfully in the future, with NRF2-activating and non-NRF2-activating NSAIDs used to treat the disorders they’re most likely to treat.
According to Eisenstein, the discoveries might lead to whole new uses for NSAIDs.

NRF2 is a transcription factor that regulates a vast number of genes involved in a variety of functions, including metabolism, immunological response, and inflammation. The protein has also been linked to anti-aging, lifespan, and the decrease of cellular stress.

Said Eisenstein, “That NRF2 does so much suggests that NSAIDs might have other effects, whether beneficial or adverse, that we haven’t yet looked for.”

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