European Journal of Scientific Research (ISSN: 1450 ... - EuroJournals

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© European Journal of Scientific Research, Vol 7, No 5, 2005
INTRODUCTION
CYP2E1 is a very important member of CYP P450 which play an important role in
xenobiotic metabolisme. This enzyme activates many toxicologically important
substrates especially carcinogen with low molecular weight to more toxic products.
CYP2E1 metabolizes more than 70 substrates including paracetamol, benzene,
dimethylnitrosamine and ethanol (1). CYP2E1 is inducible by its substrates. Induction of
CYP2E1 activity by its substrates such as ethanol can be more than ten-fold (2). Studies
in animals showed that hepatic CYP2E1 exhibits enhanced NADPH oxidase activity and
elevated production of reactive oxygen species (ROS) upon reduction by NADPH (3).
This reduction is not influenced by the presence of substrates (4).
ROS is an atom or molecule that contain one or more unpaired electron (5). ROS initiate
a process called lipid peroxidation. One radical species initiate a chain reaction that
produce more radical species and consequently cause extensive damage to the lipid
structure. Products of lipid peroxidation include short and long chain aldehyde,
phospholipid and ester cholesterol that contain aldehyde and can be used to evaluate lipid
peroxidation in a system (6). 4-Hydroxy-2-nonenal (HNE) and malondialdehyde (MDA)
are the most produced unsaturated aldehyde during this process and probably more
harmful than ROS itself. HNE for instance is a reactive and stable metabolite that have
longer half-life compare to ROS. Studies have shown that HNE involves in various
biological activity including inhibition of protein and DNA synthesis, enzyme
inactivation and promote neutrophile migration (7). Malondialdehyde can bind to
proteins and cellular constituents (8) and contribute to a variety of pathological processes
including malignant transformation (9) and fibrogenesis (10).
CYP2E1 is part of microsomal ethanol-oxidizing system (MEOS). Ethanol consumption
has been shown to result in an induction of CYP2E1 activity in the liver about four- to
ten-fold. Induction of CYP2E1 may have important consequences such as enhanced
production of acetaldehyde, a highly reactive and toxic metabolite, as well as generation
of free radicals such as hydroxyethyl radicals leading to oxidative stress (2).
Vitamin E is a generic description for all tocopherol and tocotrienol derivatives.
Tocopherols have a phytyl chain, while tocotrienols have a similar chain but with a three
double bonds at positions 3’, 7’ and 11’. Vitamin E is a well known antioxidant which
scavenge free radicals and protects against oxidative damage in cells (11). The
antioxidant properties of vitamin E depends more on phenolic group and chromanol ring
compared to the side chain (12). α-Tocopherol is the major vitamin E in vivo and exerts
the highest biological activity (13). There are some conflicting reports on the antioxidant
activities of tocopherols and tocotrienols. Previous study reported that α-tocotrienol
possessed 40- to 60-fold higher antioxidant activity than α-tocopherol against lipid
peroxidation in rat liver microsomes (14). But there are also other study which did not
show significant difference in the antioxidant activities between tocopherol and
tocotrienol (15, 16).
Theoretically, synthetic vitamin E showed the same antioxidant activity as naturally
occurring vitamin E. But classical rat foetal gestation-resorption assay showed that
synthetic tocopherol showed a defect in the biological activity compared to naturally
occurring vitamin E (17). It was proved that the structure of tocopherol is very important