The antihepatotoxic properties of
uridine-diphosphoglucose (
UDPG, Toxepasi) have been evaluated in a well-established model of liver damage, the liver fluke
infection (experimental
fascioliasis in the rat), which causes a dramatic loss of the microsomal
drug-metabolizing
monooxygenase (MFO) and
glucuronosyltransferase (GT)
enzyme systems as a consequence of peroxidative damage to microsomal
membrane lipids. Administration of 100 mg/kg
UDPG i.p. to the infested rat for the entire course of the
infection (40 days) positively affects the parameters reflecting the integrity of the liver cell (serum
glutamate-
pyruvate, GPT and
glutamate-
oxaloacetate, GOT,
transaminases) and the detoxifying capacity of the liver (
cytochrome P-450,
cytochrome b5,
cytochrome P-450-dependent
p-nitroanisole O-demethylase and
aniline hydroxylase activities, and the
p-nitrophenol glucuronidation) and greatly reduces the
lipid peroxidative phenomen in membranes from whole liver (tissue malonic dialdehyde content) and in membranes of the microsomal fraction (conjugated diene absorption). As a consequence of this, the total
lipid and
phospholipid contents of the liver are restored, there is minimal loss of latency of GT
enzyme(s),
cytochrome P-450 conversion to
cytochrome P-420 is fairly negligible and total liver
glutathione content is also restored. Therefore,
UDPG restores liver function by protecting the endoplasmic reticulum membranes from the oxidative stress resulting from activation of the CN-insensitive respiratory burst of the phagocytic cells consequent to Fasciola hepatica invasion, migration and growth. It is very likely that
UDPG acts as an effective antilipoperoxidative agent through both direct (as demonstrated by our in vitro experiments) and indirect mechanisms (stimulation of the glycolytic pathway, and hence of the reducing equivalents----
glutathione----
vitamin E supply).(ABSTRACT TRUNCATED AT 250 WORDS)