Potentiated hepatotoxicity from concurrent administration of acetaminophen and allyl alcohol to rats |
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| Authors: | H E Poulsen A Lerche N T Pedersen |
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| Affiliation: | 1. Department of Medicine A, Laboratories of Experimental Pathology, Rigshospitalet Copenhagen, Denmark;2. Department of Pathology, Rigshospitalet Copenhagen, Denmark;1. Zoology Department, Environmental Sciences Division, Faculty of Science, Mansoura University, 35516 Mansoura, Egypt;2. Department of Biological Sciences, Princes Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia;3. Deanship of Scientific Research, Princes Nora Bint Abdulrahman University, Saudi Arabia;4. Urology and Nephrology Department, Mansoura University, Egypt;1. Division of Virology, Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran;2. Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran;3. Department of Pharmacology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran;4. Department of Clinical Science, School of Veterinary Medicine, Ardakan University, Ardakan, Yazd, Iran;1. Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China; Co-innovation Center of Henan Province for New drug R & D and Preclinical Safety; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, PR China;2. Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Precision Clinical Pharmacy (Zhengzhou University), Zhengzhou 450052, PR China;1. Institute of Experimental Immunology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;2. Laboratory for Experimental Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;3. I. Medical Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;1. Department of Neurosurgery, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675 München, Germany;2. Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675 München, Germany;3. Institute of Medical Statistics and Epidemiology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675 München, Germany |
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| Abstract: | Female Wistar rats were treated with acetaminophen 3.0 g/kg BW and allyl alcohol 75 microliter/kg BW by gastric tube. Hepatic function, measured as galactose elimination capacity and prothrombin index, was reduced to about 0.40 times control value. Plasma alanine transferase activity was elevated more and earlier after treatment with acetaminophen and allyl alcohol compared to administration of acetaminophen alone. Also prothrombin index was reduced more and earlier from the combination. Hepatic glutathione was depleted to a lower level 3 hr after administration of the combination of toxins, compared to administration of acetaminophen alone, after 6 hr there was no difference. Excretion of acetaminophen metabolites, especially the acetaminophen mercapturate, into urine was not changed from the combination. After administration of the toxic combination histological changes in the liver were minor. The results indicate that the two toxins potentiate each other's action. The potentiation is proposed to be due to prevention of compensatory hyperfunction of non-necrotic liver cells rather than to direct metabolic interaction of the toxins. |
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