The liver
is one of the heaviest organs in the body (1.2-2.5kg) and serves the principle
function of maintaining the body’s internal milieu (Dayer, 1983). The
anatomical position of the liver is key to fulfilling this function as almost
all absorption of foreign material into the body takes place in the gut and the
portal blood draining the gut flows to the liver, which subsequently controls
the release of absorbed nutrients into the systemic circulation. In addition to
its function in metabolizing nutrients, the liver is able to store and release
a variety of substrates, vitamins and minerals and plays a crucial role in drug
and bilirubin metabolism. The liver is also the largest reticulo-endothelial
organ in the body and its situation is important in removing infecting bacteria
and bacterial products, which often enter the body from the gut (Dayer,
1983).
Humans are
exposed daily to a wide variety of foreign compounds called Xenobiotics
(including drugs and medicinal plants). Although every tissue has some ability
to metabolize drugs, the liver is the principle organ of drug metabolism
(Correia, 1995). Following oral administration, many drugs are absorbed intact
from the small intestine and transported first via the portal system to the
liver these reactions are assigned into two major category called phase I and
phase II reactions (Dayer 1983).
Phase I reactions usually convert the
parent drug to a more pear metabolite by introducing or unmasking a functional
group (-OH, NH2-SH). Often these metabolites are inactive, though in
some instances activity is only modified (Katzung, 1998). If phase I
metabolites are sufficiently polar, they may be readily excreted. However many
phase I products are not eliminated rapidly and undergo a subsequent reaction
in which an endogenous substrate such as glucuronic acid, sulfuric acid, acetic
acid or an amino acid combines with the newly established functional group to
form a highly polar conjugate. Such conjugation or synthetic reactions are the
hallmarks of phase 11 metabolism (Katzung, 1998). A great Variety of drugs
undergo reactions although in some instances the parent drug may already posses
a functional group that may form a conjugate directly.
PARACETAMOL AS AN AGENT OF OXIDATIVE STRESS
The Liver is the center of drug metabolism,
in the case of an overdose, the liver is overwhelmed by the drug and this can
lead to oxidative stress. Thus oxidative stress is any condition that
consistently interferes with normal body function (Katzung B, 1998)
Paracetamol is contained in many preparations
(both over- the – counter and prescription only medications). In some animals
for example cats – small doses are toxicity. Without timely treatment, overdose
can lead liver failure and death within days; paracetamol toxicity is by far,
the most common cause of acute liver failure in both the United States and the
United Kingdom (styrt et al, 1990).
It is sometimes used in suicide attempts by those unaware of
the prolonged time course and high morbidity associated with paracetamol –
induced toxicity in survivors. Thus in
this research works, paracetamol will be overdose will be administrated to rats
and analysis done to measure the extent of per oxidation