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J Fouts

Publications and source records attributed to J Fouts.

4 recordsLinked to original sources

Separation and characterization of hepatocytes from immature and adult rats into distinct subpopulations by centrifugal elutriation.

Hepatocytes were isolated from immature and adult rat liver by retrograde perfusion with calcium free buffer, followed by enzymic digestion, and separated into subpopulations by centrifugal elutriation. Several subpopulations with increasing cell diameters were distinguished. The smaller cells were attributed to the periportal area, the larger ones to the perivenous (centrilobular) region. Profiles of total cytochrome P-450 concentration, benzphetamine N-demethylation and ethoxyresorufin O-deethylation, NADPH-cytochrome c-reductase, glucose-6-phosphatase and glutamate-pyruvate-transaminase activities were determined in all subpopulations. With adult hepatocytes an increasing cytochrome P-450 concentration with increasing cell diameter (increasing from periportal to perivenous hepatocytes) could be observed, paralleled by increasing activities of benzphetamine N-demethylation and ethoxyresorufin O-deethylation activities. While NADPH-cytochrome c-reductase did not show a distinct zonation, glucose-6-phosphatase and glutamate-pyruvate-transaminase revealed increasing activities with increasing cell diameter. Immature hepatocytes (rats aged 11-15 days) were smaller, and more fragile. They could not be isolated with the same enzyme solution as adult hepatocytes and they did not show any zonation of cytochrome P-450 concentration, although the zonation of benzphetamine N-demethylation and ethoxyresorufin O-deethylation was almost fully developed. For NADPH-cytochrome c-reductase a zonation with higher activities in the perivenous cells could be demonstrated, in contrast to the lack of zonation in adult rats. Glucose-6-phosphatase activity showed a decline with increasing cell diameter in immature hepatocytes, whereas glutamate-pyruvate-transaminase activity did not show any zonation. In rats aged 20 days the zonation of these parameters in liver was in between that of younger and older animals. Zonation of the liver lobule develops postnatally with individual patterns for the different parameters.

Aging

Functional hepatocellular heterogeneity determined by the hepatotoxins allyl alcohol and bromobenzene in immature and adult Fischer 344 rats.

Adult (male, 75-90 days old) and immature rats (both sexes, 11-12 days old) were treated with allyl alcohol or bromobenzene to induce periportal or centrilobular hepatic injury, respectively. Histologically confirmed liver lesions were produced in adult rats with both treatments. In adult rats, allyl alcohol decreased hepatic cytochrome P-450, benzphetamine N-demethylation, and ethoxyresorufin O-deethylation activities all by about 30%, whereas bromobenzene influenced these parameters differently: cytochrome P-450 was lowered by 55%, benzphetamine N-demethylation by 80%, and ethoxyresorufin O-deethylation by 90%. Cytochrome c reductase, 5'-nucleotidase, glucose-6-phosphatase, and glutamate-pyruvate transaminase activities were not significantly influenced. In immature rats, allyl alcohol did not produce histopathological alterations in liver, but did lower both cytochrome P-450 concentration (30%) and ethoxyresorufin O-deethylation (75%). Benzphetamine N-demethylation was not significantly affected. Bromobenzene produced typical centrilobular liver damage and a decrease of both cytochrome P-450 (20%) and ethoxyresorufin O-deethylation (50%). Benzphetamine N-demethylation was increased slightly, but not significantly. The differences in effects of the two hepatotoxins in adult vs immature rats seem to indicate that the hepatocellular heterogeneity of xenobiotic metabolism which is seen in adult liver (perivenous vs periportal areas) is not well developed in the immature animal.

1-Propanol

Separation of immature and adult rat hepatocytes into distinct subpopulations by centrifugal elutriation.

Several subpopulations of hepatocytes with increasing cell diameters were isolated, the smaller cells were attributed to the periportal area, the larger ones to the perivenous region. Profiles of total cytochrome P-450, benzphetamine N-demethylation and ethoxyresorufin O-deethylation, cytochrome c-reductase, glucose-6-phosphatase and GPT activities were determined. With adult hepatocytes an increasing cytochrome P-450 concentration with increasing cell diameter could be observed, paralleled by increasing activities of monooxygenases. Glucose-6-phosphatase and GPT also revealed increasing activities with increasing cell diameter, but cytochrome c-reductase did not show a distinct zonation. Immature hepatocytes (age 11-15 days) were smaller, more fragile, and could not be isolated with the same enzyme solution as adult hepatocytes. They did not show any zonation of cytochrome P-450 whereas the zonation of the monooxygenases was almost fully developed. For cytochrome c-reductase a zonation with higher activities in the perivenous cells could be demonstrated, in contrast to the lack of zonation in adult rats. Glucose-6-phosphatase showed a decline with increasing cell diameter in immature hepatocytes, whereas GPT did not show any zonation. In rats aged 20 days the zonation of these parameters in liver was in between younger and older animals.

Alanine Transaminase