| Title | Paracetamol induced hepatotoxicity in rabbits and the role of prior acute ethanol consumption | |
| Authors | Maria Vagena¹, Dimitrios Dimitroulopoulos², Apostolis Papalois³, Eleni Archontaki⁴, Maria Demonakou⁵, Kostantina Giannioti6, Maria Vertzoni⁴ and Panagiota Galanopoulou6
1. Second Internal Medicine Department, Elpis Hospital, Athens, Greece 2. Gastroenterology Department, Agios Savvas Hospital, Athens, Greece 3. Experimental and Research Unit, ELPEN Pharma Co Inc., Athens, Greece 4. Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens, Athens, Greece 5. Pathology Department, Sismanoglion Hospital, Athens, Greece 6. Laboratory of Experimental Pharmacology, School of Medicine, University of Athens, Athens, Greece |
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| Citation | Vagena, M., Dimitroulopoulos, D., Papalois, A., Archontaki, E., Demonakou, M. et al: Paracetamol induced hepatotoxicity in rabbits and the role of prior acute ethanol consumption, Epitheorese Klin. Farmakol. Farmakokinet. 21(1): 5-12 (2007) | |
| Publication Date | Accepted for publication (Final version): 15 January 2007 | |
| Full Text Language | English | |
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| Keywords | Paracetamol, acetaminophen, ethanol, alcohol, liver necrosis, HPLC, CYP450, microvesicular hepatocyte degeneration, rabbits, glucoroide, toxic dose. | |
| Other Terms | review article | |
| Summary | The aim of the study was to investigate the possible mechanisms of aversion of paracetamol metabolism from cytochrome P450 after acute ethanol administration in a normal reproducible model of New Zealand white adult male rabbits. A total of 12 animals, divided in two groups of 6 (G1, G2) was used. G1 rabbits received paracetamol per os, 2 g per kg of body weight, and G2 animals, received paracetamol as above 30 min after acute ethanol 20% administration, 4g per kg of body weight. Hematological and clinical blood chemistry parameters were measured at 6, 12 and 24 h after paracetamol administration. Acetaminophen and its major metabolites levels were measured, using HPLC analysis, in blood samples collected at 1, 2, 4 and 6h after the drug administration and in urine. At the end of the experiment all animals were sacrificed. Sections from the livers, fixed in buffered formalin and stained with H-E were examined. Although the performed statistical analysis no revaled any statistically significant difference concerning the studied parameters including CYP450 activity, the statistical analysis of histologic findings revealed higher percent-age of liver necrosis (p=0.013) and lower percentage of microvesicular hepatocyte degeneration (p=0.002) for G1. The reported from other investigators protective role of ethanol against paracetamol-induced hepatotoxicity was not evident in our study. Thus, further studies are required to resolve this problem. | |
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