Ibuprofen changes liver metabolism in mice

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The painkiller ibuprofen may have more significant effects on the liver than previously thought, a new study with mice shows.

The effects are markedly different in males and females, according to the study, which appears in Scientific Reports.

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

Experts know that ibuprofen can cause heart problems and increase stroke risk, but the effects on the liver were less well understood, says Aldrin Gomes, professor in the neurobiology department at the University of California, Davis.

Researchers 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 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 says.

At least 34 different metabolic pathways were altered in male mice treated with ibuprofen. They included pathways involved in metabolism of amino acids, hormones, and vitamins as well as 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 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,” Gomes says.

“No drug is perfect, as all drugs have side effects. However, many commonly used drugs such as ibuprofen are being overused and should not be used for certain conditions such as mild pain.”

In the long term, it is important for the scientific community to start addressing differences between males and females with respect to drug metabolism and effects, he says.

Additional authors are from UC Davis. The National Institutes of Health and the American Heart Association supported the work.

Source: UC Davis