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Alteration in rat liver microsomal membranes induced by acetaminophen
Abstract:
Acetaminophen caused a reversible change in the fluorescence polarization of eosin maleimide and dansyl chloride labeled to rat liver microsomes, indicating that acetaminophen acts on microsomal membrane proteins. Acetaminophen in the presence of nicotinamide adenine dinucleotide phosphate (NADPH), brought about an irreversible change in the fluorescence polarization of the probes. Acetaminophen, with or without NADPH, was also found to change the fluorescence polarization of lipid-soluble fluorescent probes, 2- and 12-(9-anthroyloxy)stearic acid labeled to microsomes, indicating its action on microsomal membrane lipids.
Insights
Acetaminophen alters liver microsomal membranes by reversibly affecting proteins and lipids. With NADPH, these acetaminophen-induced changes become irreversible, suggesting a deeper interaction with cellular components.
Area of Science:
- Biochemistry
- Pharmacology
- Cell Biology
Background:
- Acetaminophen is a widely used analgesic and antipyretic.
- Its precise mechanism of action at the cellular level, particularly concerning liver microsomes, requires further elucidation.
- Microsomal membranes are critical for drug metabolism and cellular signaling.
Purpose of the Study:
- To investigate the effects of acetaminophen on rat liver microsomal membrane proteins and lipids.
- To determine if nicotinamide adenine dinucleotide phosphate (NADPH) influences acetaminophen's interaction with microsomes.
- To assess the reversibility of acetaminophen's impact on membrane structure.
Main Methods:
- Utilized fluorescence polarization techniques to probe changes in membrane protein and lipid environments.
- Employed fluorescent probes: eosin maleimide and dansyl chloride for proteins, and 2- and 12-(9-anthroyloxy)stearic acid for lipids.
- Examined the effects of acetaminophen with and without NADPH on labeled rat liver microsomes.
Main Results:
- Acetaminophen induced a reversible alteration in the fluorescence polarization of protein-specific probes, indicating interaction with microsomal membrane proteins.
- In the presence of NADPH, acetaminophen caused an irreversible change in protein probe fluorescence polarization.
- Acetaminophen modified the fluorescence polarization of lipid-specific probes, both with and without NADPH, suggesting an impact on microsomal membrane lipids.
Conclusions:
- Acetaminophen directly interacts with both proteins and lipids within rat liver microsomal membranes.
- The presence of NADPH enhances acetaminophen's interaction, leading to irreversible membrane alterations.
- These findings provide insight into the molecular mechanisms underlying acetaminophen's effects on cellular membranes.