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Effect of amiodarone (AMD) on the antioxidant enzymes, lipid peroxidation and mitochondrial metabolism
S M Ribeiro1, A P Campello, A J Nascimento
1Departamento de Bioquímica, Universidade Federal do Paraná, Curitiba, PR., Brazil.
Abstract:
The effects of amiodarone (AMD) on lipid peroxidation of rat liver mitochondria, the formation of superoxide anions at the respiratory chain level, and the cytosolic and mitochondrial enzymatic protective mechanisms of oxidative stress were studied. An attempt of classify AMD according to its toxic ability to interfere with the integrated function of electron transport enzymes was also investigated. The results confirm the effects of AMD on complex I and permit the placing of this drug in class A of the classification of Knobeloch, together with rotenone, amytal and chaotropic agents. AMD has no effect on the activity of the enzymes superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase, nor on glucose 6-phosphate dehydrogenase. AMD did not promote an increase in the formation of anion superoxide at the respiratory chain level. Pre-incubation with AMD (16.6 microM) inhibited about 70 per cent of lipid peroxidation. The results suggest a protective effect of AMD against lipid peroxidation in mitochondrial membranes by iron-dependent systems.
Insights
Amiodarone (AMD) protects against mitochondrial lipid peroxidation and does not increase superoxide formation. Researchers classified AMD
Area of Science:
- Biochemistry
- Toxicology
- Mitochondrial Function
Background:
- Oxidative stress is implicated in various pathologies.
- Mitochondria are key players in cellular energy production and oxidative stress.
- Amiodarone (AMD) is an antiarrhythmic drug with known side effects.
Purpose of the Study:
- To investigate the effects of amiodarone (AMD) on mitochondrial lipid peroxidation.
- To assess AMD's impact on superoxide anion formation in the respiratory chain.
- To evaluate AMD's influence on enzymatic antioxidant defense mechanisms and classify its toxicity.
Main Methods:
- Studied lipid peroxidation in rat liver mitochondria exposed to AMD.
- Measured superoxide anion formation at the respiratory chain level.
- Assessed the activity of antioxidant enzymes like superoxide dismutase, catalase, and glutathione peroxidase.
- Classified AMD's toxic potential based on its effect on electron transport enzymes.
Main Results:
- AMD confirmed to affect Complex I of the electron transport chain, classifying it in Class A.
- AMD did not alter the activity of key antioxidant enzymes or increase superoxide anion formation.
- Pre-incubation with AMD significantly inhibited lipid peroxidation by approximately 70% in mitochondrial membranes.
- AMD demonstrated a protective effect against iron-dependent lipid peroxidation.
Conclusions:
- Amiodarone exhibits protective effects against mitochondrial lipid peroxidation.
- AMD's interaction with Complex I positions it within a specific toxicity classification.
- The drug does not exacerbate oxidative stress via increased superoxide production or antioxidant enzyme inhibition.