A cytochemical study of the livers of rats treated with diethylnitrosamine/phenobarbital, with benzidine/phenobarbital, with phenobarbital, or with clofibrate

Mompon, P.; Greaves, Peter; Irisarri, E.; Monro, A. M.; Bridges, James W.

doi:10.1016/0300-483x(87)90129-6

Cited by 7 publications

(4 citation statements)

References 26 publications

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“…These differences in effects of DEHP and PB support the findings of Mompon et al (14) in a somewhat similar study, that clofibrate increased 2-glycerophosphate dihydrogenase, whereas PB did not. Thus, the biochemical effects in the liver of peroxisome-proliferators differ from those of a typical liver neoplasm promoter.…”

Section: Discussionsupporting

confidence: 81%

“…This reduction is similar to our previous findings with another peroxisome proliferator, nafenopin (1 6). In other studies, nodules (adenomas) and hepatocellular carcinomas induced by the peroxisome proliferator Wy- 14,643 have been found to be negative for GGT (22). In contrast to the reduction of GGT by peroxisome proliferators, activity in penportal hepatocytes can be increased by other xenobiotics such as butylated hydroxytoluene (7) and butylated hydroxanisole (40), as well as by PB (16,24), as in the present study.…”

Section: Discussioncontrasting

confidence: 49%

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Effects of the Peroxisome Proliferator Di(2-Ethylhexyl)Phthalate on Enzymes in Rat Liver and on Carcinogen-Induced Liver Altered Foci in Comparison to the Promoter Phenobarbital

1990

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The livers of rats given either the peroxisome proliferating hepatocarcinogen di(2-ethylhexy1)phthalate (DEHP) following initiation by 2-acetylaminofluorene (AAF) or the neoplasm promoter phenobarbital (PB)were studied for changes in 8 histochemical properties. Male F344 rats were fed 200 ppm AAF for 7 weeks to induce hepatocellular altered foci, and were then fed diets containing either no chemical, 12,000 ppm DEHP or 500 ppm PB for 24 weeks. In hepatocytes, DEHP increased alkaline phosphatase activity throughout the lobule, but reduced gamma-glutamyltransferase (GGT) activity in penportal hepatocytes. PB, in contrast, increased GGT activity in penportal hepatocytes. In foci that were induced by AAF, DEHP reduced the histochemical activity of GGT and did not increase the number, mean volume or volume % of foci detected by deficiencies in iron storage, glucose-6-phosphatase, adenosine triphosphatase or fibronectin. PB enhanced the expression of all 8 phenotypic abnormalities in foci such that either more profiles were detected or the area of foci was increased.

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Section: Discussionsupporting

confidence: 81%

Section: Discussioncontrasting

confidence: 49%

Effects of the Peroxisome Proliferator Di(2-Ethylhexyl)Phthalate on Enzymes in Rat Liver and on Carcinogen-Induced Liver Altered Foci in Comparison to the Promoter Phenobarbital

1990

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“…Rapid upregulation of G6PD activity at the post-translational level was demonstrated after treatment of animals or cells with hormones (Lombardi et al 2000), GSH-depleting agents (Salvemini et al 1999), and growth factors (Stanton et al 1991). In our model, DENA was administered to rats to induce (pre)neoplasms in livers, and it has been established that an early effect of DENA is depletion of reduced glutathione (Mompon et al 1987). A direct consequence of increased G6PD activity is regeneration of reduced glutathione.…”

Section: Discussionmentioning

confidence: 99%

Post-translational Regulation of Glucose-6-phosphate Dehydrogenase Activity in (Pre)neoplastic Lesions in Rat Liver

Frederiks

Bosch

Jong

et al. 2003

J Histochem Cytochem.

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S U M M A R Y Glucose-6-phosphate dehydrogenase (G6PD; EC 1.1.1.49) is the key regulatory enzyme of the pentose phosphate pathway and produces NADPH and riboses. In this study, the kinetic properties of G6PD activity were determined in situ in chemically induced hepatocellular carcinomas, and extralesional and control parenchyma in rat livers and were directly compared with those of the second NADPH-producing enzyme of the pentose phosphate pathway, phosphogluconate dehydrogenase (PGD). Distribution patterns of G6PD activity, protein, and mRNA levels were also compared to establish the regulation mechanisms of G6PD activity. In (pre)neoplastic lesions, the V max of G6PD was 150-fold higher and the K m for G6P was 10-fold higher than in control liver parenchyma, whereas in extralesional parenchyma, the V max was similar to that in normal parenchyma but the K m was fivefold lower. This means that virtual fluxes at physiological substrate concentrations are 20-fold higher in lesions and twofold higher in extralesional parenchyma than in normal parenchyma. The V max of PGD was fivefold higher in lesions than in normal and extralesional liver parenchyma, whereas the K m was not affected. Amounts of G6PD protein and mRNA were similar in lesions and in extralesional liver parenchyma. These results demonstrate that G6PD is strongly activated post-translationally in (pre)neoplastic lesions to produce NADPH.

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“…Of these, methylene dianiline and galactosamine are model compounds for the induction of bile duct damage and hepatocyte death, respectively, in a reproducible and dose‐dependent manner in experimental animals (Keppler et al 1974; Kanz et al 1992 & 1995; Beckwith‐hall et al 1998). Clofibrate is a well‐documented hepatotoxicant that causes peroxisome proliferation and tumours without necrosis in the rodent liver (Mompon et al 1987).…”

mentioning

confidence: 99%

A Metabonomics Study of the Hepatotoxicants Galactosamine, Methylene Dianiline and Clofibrate in Rats*

Ishihara

Katsutani

Aoki

2006

Basic Clin Pharma Tox

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Abstract:The efficacy of high-resolution 1 H nuclear magnetic resonance ( 1 H-NMR) spectroscopy-based metabonomics was studied in a model of rat liver toxicity. Hepatotoxicities were induced in male rats using methylene dianiline, clofibrate and galactosamine. Twenty-four-hr urine from days 1 to 5 after treatment were subjected to 1 H-NMR evaluation of the biochemical effects. Blood were also taken at Days 2, 3 and 5 to examine biochemical changes associated with hepatotoxicities, and histopathological changes were evaluated at termination. Increases in liver enzymes were observed in animals treated with methylene dianiline or galactosamine, and histopathological analysis revealed changes associated with hepatobiliary damage and hepatocellular necrosis in methylene dianiline-and galactosamine-treated animals, respectively. Principal component analysis and statistical Spotfire analyses were used to visualize similarities and differences in urine biochemical profiles produced by 1 H-NMR spectra. The biochemical effects of methylene dianiline and galactosamine were characterized by elevated levels of glucose, fructose, b-hydroxybutyrate, alanine, acetoacetate, lactate and creatine and decreased levels of hippurate, 2-oxoglutarate, citrate, succinate, trimethylamine-N-oxide, taurine and N-acetylglutamate in rat urine. Clofibrate treatment elevated the levels of N-methylnicotinamide and 3,4-dihydroxymandelate and decreased the levels of 2-oxoglutarate and N-acetylaspartate. This work shows that combinations of 1 H-NMR and pattern recognition are powerful tools in the evaluation of the biochemical effects of xenobiotics in liver.

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A cytochemical study of the livers of rats treated with diethylnitrosamine/phenobarbital, with benzidine/phenobarbital, with phenobarbital, or with clofibrate

Cited by 7 publications

References 26 publications

Effects of the Peroxisome Proliferator Di(2-Ethylhexyl)Phthalate on Enzymes in Rat Liver and on Carcinogen-Induced Liver Altered Foci in Comparison to the Promoter Phenobarbital

Effects of the Peroxisome Proliferator Di(2-Ethylhexyl)Phthalate on Enzymes in Rat Liver and on Carcinogen-Induced Liver Altered Foci in Comparison to the Promoter Phenobarbital

Post-translational Regulation of Glucose-6-phosphate Dehydrogenase Activity in (Pre)neoplastic Lesions in Rat Liver

A Metabonomics Study of the Hepatotoxicants Galactosamine, Methylene Dianiline and Clofibrate in Rats*

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