New York: Researchers, including one of an Indian-origin, have found that the popular painkiller ibuprofen may have more significant effects on the liver than previously thought.

Ibuprofen belongs to a group of drugs called nonsteroidal anti-inflammatory drugs, or NSAIDs, widely used over the counter to treat pain and fever.

The study, published in the journal Scientific Reports, picked mice for an experiment and showed marked differences between males and females.

"It's well-established that ibuprofen can cause heart problems and increase stroke risk, but the effects on the liver were less well understood, said study researcher Aldrin Gomes, Professor at University of California, Davis (UC Davis) in the US.

For the findings, Gomes, postdoctoral Indian-origin researcher Shuchita Tiwari and colleagues dosed mice with a moderate amount of ibuprofen for a week - equivalent to an adult human taking about 400 mg of the drug daily.

Then they used advanced mass spectrometry at the UC Davis' Proteomics Core Facility to capture information on all the metabolic pathways in liver cells.

"We found that ibuprofen caused many more protein expression changes in the liver than we expected," Gomes said.

According to the researchers, at least 34 different metabolic pathways were altered in male mice treated with ibuprofen.

They included pathways involved in the metabolism of amino acids, hormones, and vitamins as well as the production of reactive oxygen and hydrogen peroxide inside cells. Hydrogen peroxide damages proteins and stresses liver cells.

The researchers found that ibuprofen had different, and in some cases opposite, effects in the livers of male and female mice.

For example, the proteasome - a waste-disposal system that removes unwanted proteins - responded differently in males and females. Ibuprofen elevated the activity of cytochrome P450, which breaks down drugs, in females but decreased it in males.

"The elevation in cytochrome P450 could mean that other drugs taken with ibuprofen could stay in the body for a longer duration in males and this has never been shown before. No drug is perfect, as all drugs have side effects," Gomes said.

However, many commonly used drugs such as ibuprofen are being overused and should not be used for certain conditions such as mild pain," Gomes concluded.

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