Comparison of Effects of Acetaminophen on Liver Microsomal Drug Metabolism and Lipid Peroxidation in Rats and Mice

Satoh, Takaya; Kitagawa, Haruo

doi:10.1254/jjp.28.485

Cited by 6 publications

(3 citation statements)

References 16 publications

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“…Consistent hepatotoxicity has been shown in murine and hamster models. 43,[52][53][54][55][56][57] Moreover, this damage occurs in a dose-dependent manner and at the same dose levels that cause damage in humans. 54,55 Consequently, murine models have been widely adopted for the investigation of the pathophysiological characteristics of FHF.…”

Section: Acetaminophen Modelsmentioning

confidence: 99%

Animal models of fulminant hepatic failure: A critical evaluation

et al. 2000

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Few conditions in medicine are more dramatic or more devastating than acute liver failure. Our understanding and treatment of this condition have been limited by the lack of satisfactory animal models. The most widely used models consist of surgical anhepatic and devascularization procedures and hepatotoxins, such as galactosamine and acetaminophen. Potential disadvantages with surgical models are their inability to recreate the inflammatory milieu that exists in acute liver failure and their reliance on surgical expertise. Models using hepatotoxins are free of such constraints. Galactosamine-induced hepatotoxicity is more predictable than acetaminophen, but its cost and lack of a human equivalent clinical syndrome has restricted its use. Acetaminophen-based models offer the greatest potential but have proven the most difficult to develop because of difficulties with reproducibility and refractory anemia. Although progress has been made, research must continue in this area to establish an animal model with minimal disadvantages that would accurately reflect the clinical syndrome seen in humans.

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Section: Acetaminophen Modelsmentioning

confidence: 99%

Animal models of fulminant hepatic failure: A critical evaluation

et al. 2000

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“…Acetaminophen is metabolized by enzymes in liver microsomes and produces a hepatotoxic metabolite, N-hydroxy-acetaminophen (18)(19)(20).…”

Section: Absorption Of Salicylamide From the Intestinal Tractmentioning

confidence: 99%

Vascularly perfused rat small intestine: A research model for drug absorption.

et al. 1980

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Abstract-Rat isolated small intestine was perfused at a fixed flow rate through the superior mesenteric artery with whole rat blood recycled from a devised oxygenator reservoir. As indicated by perfusion pressure, tissue glucose and oxygen consumption, and histological studies, the perfused intestine remained in a viable state over the perfusion period of 2 hr. Rapid absorption of glucose from the intestinal tract was observed after the intraduodenal injection. When single doses of acetaminophen were injected into the duodenal lumen or poured over the perfused intestine, the ab sorption was rapid and dose-dependent.Shortly after single intraduodenal injections of salicylamide, salicylamide in free and conjugated forms (sulfate and glucuronide) appeared in the circulating blood. These results indicate that the vascularly perfused intestinal preparation has wide applications in biochemical experimental fields.Numerous investigations have been concerned with attempts to develop useful pre parations for evaluating functions of the intestine. Most of these studies for uptake, me tabolism and transport of substrates by intestinal epithelial cells have been performed on isolated preparations immersed in physiological salt solution, e.g., intestinal rings, sheets of mucosa and serosa, and isolated villi (1-3). Although these preparations provided pertinent information leading to investigations of biochemical problems related to absorption and metabolism of drugs, there were drawbacks. Kavin et al. (4) and Windmueller et al. (5) devised an isolated intestinal preparation of the rat sustained by vascular perfusion with washed bovine red blood cells suspended in an "artificial plasma" and with rat whole blood, respectively, then carried out studies on viability. Their preparations appeared to be parti cularly suitable for examining entry of drugs from the intestinal tract into the blood or lymph vessels. However, most of the studies pertaining to drug absorption and metabolism have not been carried out in such preparations, and to our knowledge there is only one study, recently reported, which dealt with absorption of antipyrine, salicylic acid and urea (6).Thus, we examined absorption and metabolism of several drugs in the intestine, using the rat isolated small intestinal preparation sustained by perfusing the mesenteric vasculatures with whole rat blood recycled from a devised oxygenator-reservoir. MATERIALS AND METHODSMale Sprague-Dawley rats (130-150 g) were deprived of food overnight before the

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“…Protein content was quantitated using bicinchoninic acid protein assay reagents purchased from Pierce Chemical Co. (Rockford, IL, USA). Contents of CYP3A29, NPR and cytochrome b5 were measured by spectral methods [20][21][22]. Western blotting was performed with mouse anti-human CYP3A4 monoclonal antibody HL3 (Santa cruz biotechnology, inc) (dilution 1:1000) and goat anti-mouse IgG with HRP labeled (dilution 1:20000).…”

Section: Heterologous Expression Of Cyp3a29 In Sf9 Cellsmentioning

confidence: 99%

Transcriptional Profile of CYP3As and Functional Expression of CYP3A29 from Piglets

Yao

Liu

Dai

et al. 2009

2009 3rd International Conference on Bioinformatics and Biomedical Engineering

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Expression profile of CYP3A individuals from piglets and characterization of CYP3A29 were investigated. Real-Time PCR showed that the liver and small intestines present the highest expression levels of CYP3A29, a human CYP3A4 homolog. The CYP3A29 was functional expressed in Bac-to-Bac baculovirus expression system together with NADPH p450 reductase (NPR) and cytochrome b5. For nifedipine oxidation (NOD) activity, recombinant CYP3A29 system showed similar enzyme kinetic parameters (Km=14.1 ～ 25.3 μM) to human recombinant CYP3A4, and a little variant to liver microsomes (Km=29.6 ～ 45.2 μM) from piglets. The NOD activity of recombinant CYP3A29 was strongly inhibited by ketoconazole (KET) and troleandomycin (TAO), and was slightly changed by inhibitors for other p450 enzymes from human. These results provided in detailed information of the characterizations of CYP3A29. We conclude from these results that caution should be hold when specific inhibitors or probes for human p450 enzymes are employed to investigate the veterinary drug metabolism.

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Comparison of Effects of Acetaminophen on Liver Microsomal Drug Metabolism and Lipid Peroxidation in Rats and Mice

Cited by 6 publications

References 16 publications

Animal models of fulminant hepatic failure: A critical evaluation

Animal models of fulminant hepatic failure: A critical evaluation

Vascularly perfused rat small intestine: A research model for drug absorption.

Transcriptional Profile of CYP3As and Functional Expression of CYP3A29 from Piglets

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