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Ibuprofen-induced liver mitochondrial permeability transition
1Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia. alnasser@kacst.edu.sa
Abstract:
This study examined the effect of the nonsteroidal anti-inflammatory drug ibuprofen on liver inner mitochondrial membrane permeability transition in the presence of Ca2+ and phosphate. Incubation of isolated liver mitochondria with ibuprofen (0.1-0.4 mM) induced inner mitochondrial membrane permeability as indicated by loss of inner mitochondrial membrane potential, swelling of matrix and loss of pre-accumulated Ca2+. The presence of cyclosporin A (1 microM) in the incubation medium preventing ibuprofen from causing loss of inner mitochondrial membrane potential, swelling and loss of pre-accumulated Ca2+. It is concluded that ibuprofen acted as an activator of Ca2+ and phosphate in promoting the opening of inner mitochondrial membrane pore.
Insights
Ibuprofen, a common anti-inflammatory drug, can disrupt liver mitochondria function by increasing membrane permeability. Cyclosporin A prevents this effect, suggesting ibuprofen activates a specific mitochondrial pore.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Mitochondrial inner membrane permeability transition (MIPT) is a critical process.
- Dysregulation of MIPT is implicated in various pathologies.
- Nonsteroidal anti-inflammatory drugs (NSAIDs) can affect cellular functions.
Purpose of the Study:
- To investigate the impact of ibuprofen on liver mitochondrial inner membrane permeability.
- To determine the role of calcium (Ca2+) and phosphate in ibuprofen-induced MIPT.
- To explore the potential protective effect of cyclosporin A.
Main Methods:
- Isolated rat liver mitochondria were used.
- Incubation with varying concentrations of ibuprofen (0.1-0.4 mM).
- Assessment of mitochondrial membrane potential, matrix swelling, and Ca2+ retention.
Main Results:
- Ibuprofen induced MIPT, evidenced by loss of membrane potential, matrix swelling, and Ca2+ release.
- Cyclosporin A (1 microM) effectively inhibited ibuprofen-induced MIPT.
- These effects were observed in the presence of Ca2+ and phosphate.
Conclusions:
- Ibuprofen acts as an activator of the mitochondrial pore opening.
- Ca2+ and phosphate are key components in ibuprofen-induced MIPT.
- Cyclosporin A demonstrates a protective role against ibuprofen's mitochondrial effects.