| Title | Additive hepatoprotective effect of silybinin, naringenin and cimetidine against paracetamol-induced hepatotoxicity in rabbits | |
| Authors | K. Giannioti¹, A. Papalois², S. Theocharis³, C. Liapi¹, N. Drakoulis⁴ and P. Galanopoulou¹
1. University of Athens, Medical School, Laboratory of Experimental Pharmacology 2. Experimental Research Unit, ELPEN Pharma 3. University of Athens, Medical School, Department of Clinical and Laboratory Medicine 4. University of Athens, Faculty of Pharmacy, Department of Pharmaceutical Technology |
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| Citation | Giannioti, K., Papalois, A., Theocharis, S., Liapi, C., Drakoulis, N. et al: Additive hepatoprotective effect of silybinin, naringenin and cimetidine against paracetamol-induced hepatotoxicity in rabbits, Epitheorese Klin. Farmakol. Farmakokinet. 20(2): 90-93 (2006) | |
| Publication Date | Accepted for publication: 19-20 May 2006 | |
| Full Text Language | English | |
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| Keywords | Paracetamol, silybinin, naringenin, cimetidine, hepatoprotection. | |
| Other Terms | review article | |
| Summary | Paracetamol is the first-line analgesic in many countries because of its safety and efficacy in therapeutic doses. Paracetamol overdose accounts for many self-poisoning hospital admissions and is the commonest cause of acute liver failure worldwide. The mechanism of Paracetamol toxicity consists in the initial formation of the reactive metabolite N-acetyl-p-benzo-quinone-imine which is mediated by cytochrome P450 enzymes. In this study we examined the hepatoprotective effect of three compounds: 1) Silybinin, a flavonoid derived from the dried fruits of Silybum Marianum Gaertn., 2) Naringenin, an antioxidant constituent of many Citrus fruits, which is also found in grapefruit juice (Citrus Paradisi Macfad., Rutaceae) and 3) Cimetidine, an H2-antagonist. All three compounds are known to be inhibitors of cytochrome P450 oxidation. The effect of these substances after acute Paracetamol poisoning in 66 healthy male New Zealand rabbits was examined, in an effort to discover more effective compounds with less adverse reactions as antidotes against Paracetamol-induced hepatotoxicity. Administration of Silybinin or Cimetidine, but not Naringenin, as a single agent improved the biochemical profile of the animals and caused less hepatic necrosis and inflammation, comparing to the animals that received no antidote or those that received the present antidote N-acetylcysteine. The combination of three drugs resulted in an additive hepatoprotective effect that can be compared to the effect of the present antidote against Paracetamol overdose, N-acetylcysteine. These compounds or others with similar mechanism of hepatoprotective action can be used as models in order to develop safer and more effective antidotes against Paracetamol poisoning in the future. | |
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Online ISSN 1011-6575
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