Gligor V.^*, Lazar E.^*, Gligor R.^**, Potencz E.^**

^* University V. Goldis, Arad, Romania
^** University of Medicine and Pharmacy, Timisoara, Romania

It is well established that the oxidative metabolism of Paracetamol by the liver generates an active metabolite (N-acetyl-p-benzoquinone-imine-NAPQ) which is detoxified by reduced glutathion (GSH) - with formation of mercapturic acid, which is than eliminated through urine excretion. In case of a treatment with toxic doses of Paracetamol, there will be a hepatic depletion of reduced glutathione as well as a rise in cytosolic calcium concentration.
The aim of the present study was to evaluate the protective effect of caffeine (100 mg/kg b/w) over the hepatotoxicity induced by a single overdose of Paracetamol (500 mg/kg b/w) administered intraperitonealy to mice, compared to the effect of a calcium channel blocker - Diltiazem (24 mg/kg b/w).
We evaluated the mortality rate of all animals, the length of hexobarbital induced sleep, the disproteinemia, the liver weight, the serum transaminase activity (ALAT, ASAT), the serum activity of alkaline phosphatase, and the variation in biochemical steady state values, as well as the histo-pathological changes.
We found favorable general effects for the caffeine treated mice as follows: an increased survival rate and a decrease in liver injuries (as we deduced from the ALAT and ASAT activity and from the partial reduction in histological changes that usually follow Paracetamol intoxication). As a conclusion Paracetamol is less toxic if administered in association with caffeine, which could be useful in the treatment of Paracetamol intoxication in humans.