Ibuprofen causes mitochondrial and proteasome dysfunction in murine hearts

Abstract

Ibuprofen is one of the most commonly used compounds in the treatment of pain, fever, and inflammation. Despite its beneficial effects, the long-term use of ibuprofen has been previously associated with increased risks for cardiovascular diseases and all-cause mortality. Relatively little is known about the signaling pathways or mechanism(s) involved in ibuprofen’s ability to increase the risk of cardiovascular diseases. Very little is also known about sex-related differences with respect to ibuprofen. We investigated the effects of ibuprofen (100 mg/kg/day, equivalent to about a 500mg tablet/day for humans) on mouse hearts using proteomics. Proteomic results suggest that female mice hearts exposed to ibuprofen for 7 days had tenfold more changes than male mice hearts exposed to ibuprofen for 7 days. Both the expression and activity of β5i immunoproteasome was significantly increased in female mice heart relative to ibuprofen-treated male heart mice. Ibuprofen treatment altered mitochondrial function in both male and female mice. Ibuprofen also induced ROS generation and decreased mitochondrial membrane potential in both male and female mice. However, ibuprofen attenuated mitochondrial complex I activity only in female hearts. Several other signaling pathways were also altered only in female mouse hearts. This study found major ibuprofen-mediated selective effects on male and female mice hearts, with specific sex differences in mitochondrial and proteasome function in mice hearts. NIEHS/Superfund P42 ES004699 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.