Search results for "Peroxisome Proliferation"

The metabolism of mono-(2-ethylhexyl) phthalate (MEHP) and liver peroxisome proliferation in the hamster.

1988

This study has investigated the in vivo metabolism of mono-(2-ethylhexyl) phthalate (MEHP), the initial metabolite of di-(2-ethylhexyl) phthalate in mammals, and the hepatic peroxisome proliferation induced by this compound following multiple oral administration to hamsters. Hamsters received [14C]-MEHP, by gavage, at doses of 50 and 500 mg/kg body wt on each of three consecutive days. Urine was collected every 24 hours and metabolite profiles were determined using capillary gas-chromatography. Multiple high doses of MEHP (500 mg/kg) induced a change in the relative proportions of metabolites produced. As previously reported for the rat, metabolites derived from sequential ω-following by β…

Peroxisome proliferation in rodents and human: A model of cell organelle biogenesis

1995

Human HepG2 and rat Fao hepatic-derived cell lines show different responses to ciprofibrate, a peroxisome proliferator: analysis by flow cytometry.

1996

Abstract Peroxisome proliferators, and especially hypolipidemic drugs such as ciprofibrate, are known to be hepatocarcinogens in rodents, but their effect in humans is controversial. In an attempt to investigate the effects of ciprofibrate at a cellular level, the analysis of individual whole cells was performed by flow cytometry on samples from two hepatic-derived cell lines: the rat Fao cell line and the human HepG2 cell line. The increase of light scatter signals in rat Fao cells treated for 3 days with ciprofibrate at 250 μMwas related to modifications of intrinsic cellular parameters, such as size and cytoplasmic granularity. Conversely, no variations appeared in human HepG2-treated ce…

Peroxisomes: biochemistry, molecular biology and genetic diseases— a video programme for teaching students

2000

Abstract Peroxisome proliferation in rodent liver is a good biochemical marker of toxicology for several classes of xenobiotics, including fibrates; phthalates and adipates; or chlorophenoxy-acetate, a herbicide. Research in peroxisomes provides a good example of the integration of fields related to basic sciences and biomedical and industrial health. A 25 min video programme illustrates techniques involved in the characterization of purified peroxisomes ( Fig. 1 Download high-res image (70KB) Download full-size image Fig. 1 . Electron microscope view of isolated peroxisomes (from rat liver ×50 000). ) and membranes, immunoblotting, measurement of proliferation markers, mRNA analysis at the…

Recent European Food Safety Authority toxicological evaluations of major phthalates used in food contact materials

2009

During the 1980s and 1990s, and at the EU level, the Scientific Committee for Food evaluated a number of phthalates that were being used, or were requested for use, as additives in plastics. At this time, peroxisome proliferation was considered as the pivotal effect on which toxicological evaluation of these chemicals was based. At the end of 1990s, a general consensus has been agreed that rodents are highly sensitive to the phenomenon of peroxisome proliferation and that this particular effect should not be used for human risk assessment. Consequently in 2004, it was requested from the newly created European Food Safety Authority to perform a new evaluation of the mainly used phthalates on…

Functional significance of the two ACOX1 isoforms and their crosstalks with PPARα and RXRα

2010

Disruption of the peroxisomal acyl-CoA oxidase 1 (Acox1) gene in the mouse results in the development of severe microvesicular hepatic steatosis and sustained activation of peroxisome proliferator-activated receptor-alpha (PPARalpha). These mice manifest spontaneous massive peroxisome proliferation in regenerating hepatocytes and eventually develop hepatocellular carcinomas. Human ACOX1, the first and rate-limiting enzyme of the peroxisomal beta-oxidation pathway, has two isoforms including ACOX1a and ACOX1b, transcribed from a single gene. As ACOX1a shows reduced activity toward palmitoyl-CoA as compared with ACOX1b, we used adenovirally driven ACOX1a and ACOX1b to investigate their effica…

Induction of the peroxisome proliferator activated receptor by fenofibrate in rat liver

1992

AbstractThe process of peroxisome proliferation in rodent liver by hypolipidemic compounds and related substances has recently been shown to be receptor-madiated. In the present study, we have examined the effect of oral administration of the strong peroxisome proliferator fenofibrate on the hepatic expression level of the peroxisome proliferator activated receptor (PPAR) in rats. Immunoblots of rat liver cytosols and nuclear extracs using antibodies raised against recombinant PPAR/β-galactosidase fusion proteins revealed a pronounced increase in the amount of PPAR protein in response to fenofibrate treatment. This induction could also be confirmed at the level or RNA by Northern blotting. …

Effects of peroxisome proliferator-activated receptor alpha activation on pathways contributing to cholesterol homeostasis in rat hepatocytes

2004

International audience; Peroxisome proliferator-activated receptor alpha (PPARa) activation by fibrates controls expression of several genes involved in hepatic cholesterol metabolism. Other genes could be indirectly controlled in response to changes in cellular cholesterol availability. To further understand how fibrates may affect cholesterol synthesis, we investigated in parallel the changes in the metabolic pathways contributing to cholesterol homeostasis in liver. Ciprofibrate increased HMG-CoA reductase and FPP synthase mRNA levels in rat hepatocytes, together with cholesterogenesis from [14C] acetate and [3H] mevalonate. The up-regulation observed in fenofibrate- and WY-14,643-treate…

Regio- and stereo-selectivity in the induction of peroxisome proliferation by substituted hexanoic acids

1993

Summary Quantitative structure-activity relationship is an effective tool in order to predict drug potency. A similar approach is actually developed for peroxisome proliferation induced by substituted carboxylic acids issued from plasticizer metabolism in rats. The study is focused on acids found in rat urine after adipic diester dosings. Size, location of the substituted group and length of the chain have been studied. 3-D structure has also been taken in account for 2-ethyl hexanoic acids. The results obtained so far demonstrate that peroxisome proliferation potencies of the considered acids are modified according structure changes. At this time location of the group along the chain appea…

Expression of liver peroxisomal proteins as compared to other organelle marker enzymes in rats treated with hypolipidemic agents.

1990

Abstract Peroxisome proliferation induced by 2 hypolipidemic agents (clofibrate and ciprofibrate) was studied in rats by complementary approaches, ie cell fractionation, electron microscopy, marker enzyme activities, immunoblotting and nucleic acid hybridization techniques. Administration of clofibrates for 2 and 52 weeks in doses of 500 ppm and 50 ppm respectively, or ciprofibrate for 2,28 and 52 weeks in doses of 250, 25 and 25 ppm respectively, did not alter the behavior of the peroxisomes after induction as shown by ultracentrifugation profiles. The peroxisome mass was increased as shown by the purification procedure. Specific enzymes (catalase and mostly cyanide insensitive palmitoyl C…