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Published on: October 12, 2017
Effect of dietary vitamin E on methyl ethyl ketone peroxide damage to microsomal cytochrome P-450 peroxidase
Abstract:
The effect of dietary vitamin E on in vivo and in vitro damage by methyl ethyl ketone peroxide (MEKP) to cytochrome P-450 and its associated enzymatic activity was studied. In vivo, MEKP damaged microsomal cytochrome P-450 and cytochrome P-450-mediated peroxidases in vitamin E-deficient rat liver. Dietary vitamin E treatment of rats protected the microsomal enzymes from peroxide damage. In vitro, the extent of MEKP inhibition was different for tetramethylphenylenediamine (TMPD)-peroxidase, NADH-peroxidase, and aminopyrine demethylase. In vitro addition of MEKP induced production of more thiobarbituric acid reacting substances (TBARS) in liver microsomes from vitamin E-deficient rats than from vitamin E-supplemented rats. When NADH and/or NADPH were supplied as reductants of MEKP, the inhibition of aminopyrine demethylase activity and the generation of TBARS by added MEKP were markedly reduced. In vivo, adequate levels of vitamin E and of NADH and NADPH are probably necessary to provide important protection to the endoplasmic reticulum during metabolism of toxic organic peroxides, such as MEKP.
Insights
Dietary vitamin E protects against methyl ethyl ketone peroxide (MEKP) damage to liver enzymes. Supplementation with vitamin E and reductants like NADH/NADPH is crucial for endoplasmic reticulum protection from toxic peroxides.
Area of Science:
- Biochemistry
- Toxicology
- Nutritional Science
Background:
- Methyl ethyl ketone peroxide (MEKP) is a toxic organic peroxide.
- Cytochrome P-450 enzymes are vital for metabolizing xenobiotics and endogenous compounds.
- Oxidative stress can damage cellular components, including microsomal enzymes.
Purpose of the Study:
- To investigate the protective effects of dietary vitamin E against MEKP-induced damage to cytochrome P-450 and associated enzymes.
- To elucidate the role of vitamin E and reductants (NADH, NADPH) in mitigating MEKP toxicity in vivo and in vitro.
Main Methods:
- In vivo studies using vitamin E-deficient and supplemented rats.
- In vitro assays measuring enzyme activity (aminopyrine demethylase, TMPD-peroxidase, NADH-peroxidase) and thiobarbituric acid reacting substances (TBARS) production.
- Administration of MEKP to rat liver microsomes.
Main Results:
- MEKP caused significant damage to microsomal cytochrome P-450 and peroxidases in vitamin E-deficient rats.
- Dietary vitamin E supplementation protected these enzymes from MEKP-induced damage.
- In vitro, MEKP inhibited enzyme activities differently, and induced more TBARS in microsomes from deficient rats.
- NADH and NADPH significantly reduced MEKP's inhibitory effects and TBARS generation.
Conclusions:
- Dietary vitamin E plays a critical role in protecting against MEKP-induced oxidative damage to liver microsomal enzymes.
- Adequate levels of vitamin E, NADH, and NADPH are essential for protecting the endoplasmic reticulum from toxic organic peroxides like MEKP.
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