scholarly journals Suppression of Peroxisomal Enzyme Activities and Cytochrome P450 4A Isozyme Expression by Congeneric Polybrominated and Polychlorinated Biphenyls

PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-5 ◽  
Author(s):  
Larry W. Robertson ◽  
Isabelle Berberian ◽  
Tim Borges ◽  
Li-Chuan Chen ◽  
Ching K. Chow ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Enzyme Activities ◽  
Corn Oil ◽  
Fatty Acyl ◽  
Male Rat ◽  
Ah Receptor ◽  
Peroxisome Proliferator ◽  
Sprague Dawley ◽  
Peroxisomal Enzyme ◽  
Cytochrome P450 4A

The purpose of this study was to determine the effects of PCBs and PBBs on peroxisome proliferator-activated receptor-α-(PPARα-) associated enzyme activities or protein levels. Male Sprague-Dawley rats were administered a single IP injection (150 μmol/kg) of either 3,3′,4,4′-tetrabromobiphenyl, 3,3′,4,4′-tetrachlorobiphenyl, 3,3′,5,5′-tetrabromobiphenyl, 2′,3,3′,4,5-pentachlorobiphenyl, 3,3′,4,4′,5-pentachlorobiphenyl, 2,2′,3,3′,5,5′-hexachlorobiphenyl, or 3,3′,4,4′,5,5′-hexabromobiphenyl in corn oil (10 ml/kg). One week later, the activities of catalase, peroxisomal fatty acyl-CoA oxidase, and peroxisomal beta-oxidation as well as cytochrome P450 4A (CYP4A) protein content were determined in subcellular liver fractions. None of the peroxisomal enzyme activities were significantly increased by any of the halogenated biphenyl congeners tested. Except for minor (approx. 25%) increases in the total CYP4A content following treatment with 2,2′,3,3′,5,5′-hexachlorobiphenyl and 3,3′,5,5′-tetrabromobiphenyl, CYP4A protein contents were not increased by any treatment. The two Ah receptor agonists, 3,3′,4,4′-tetrabromobiphenyl and 3,3′,4,4′,5-pentachlorobiphenyl, significantly diminished the liver content of CYP4A proteins and activities of the peroxisomal enzymes studied. Since a range of congeners with different biologic and toxicologic activities were selected for this study, it may be concluded that the polyhalogenated biphenyls do not induce peroxisome proliferation in the male rat, but rather certain members of this class of compounds down regulate peroxisome-associated enzymes. Since PCBs and PBBs do not increase enzyme activities and expression of proteins associated with PPARα, these agents are therefore exerting their carcinogenic and promoting activities by some other mechanism.

Quantitation of Peroxisome Proliferation using Silver Enhanced Immunogold Labeling on Glycol Methacrylate (GMA) Sections

1998 ◽  
Vol 4 (S2) ◽  
pp. 1094-1095
Author(s):  
G.D. Gagne ◽  
A.H. Illi ◽  
D. Hickman ◽  
J.A. Fagerland
Keyword(s):  
Protein A ◽  
Tumor Development ◽  
Acrylic Resin ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferation ◽  
Sprague Dawley ◽  
Peroxisomal Enzyme ◽  
Glycol Methacrylate ◽  
Sprague Dawley Rats ◽  
Safety Studies

Assessment of peroxisome proliferation is important in drug safety studies, since peroxisome proliferation often precedes tumor development in rodents. Proliferation can be measured morphometrically on sections by immunostaining for the peroxisomal enzyme catalase. Previous studies have used tissue embedded in acrylic resins such as LR White, which requires tissue sizes of 1-2 mm. Glycol methacrylate (GMA) is an acrylic resin that preserves antigenicity in much larger pieces of tissue. In this study we applied immunogold-silver staining (IGSS) to GMA sections for the quantitation of peroxisome proliferation in rat livers.Sprague-Dawley rats were given clofibrate, a known peroxisome proliferator, for 14 days. Livers were removed, fixed in neutral buffered formalin for 4 hours, and embedded in GMA. Sections (3 μm thick) were incubated with antibody to catalase followed by protein A-gold (PAG), and the gold label was amplified using a commercial silver enhancement kit. Tissue sections were counterstained with propidium iodide (PI).

scholarly journals Peroxisome Proliferator-Activated Receptor-αActivation Decreases Mean Arterial Pressure, Plasma Interleukin-6, and COX-2 While Increasing Renal CYP4A Expression in an Acute Model of DOCA-Salt Hypertension

PPAR Research ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Dexter L. Lee ◽  
Justin L. Wilson ◽  
Rong Duan ◽  
Tamaro Hudson ◽  
Ahmed El-Marakby
Keyword(s):  
Blood Pressure ◽  
Cytochrome P450 ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Interleukin 6 ◽  
Corn Oil ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Salt Hypertension ◽  
Cox 2

Peroxisome proliferator-activated receptor-alpha (PPAR-α) activation by fenofibrate reduces blood pressure and sodium retention during DOCA-salt hypertension. PPAR-αactivation reduces the expression of inflammatory cytokines, such as interleukin-6 (IL-6). Fenofibrate also induces cytochrome P450 4A (CYP4A) and increases 20-hydroxyeicosatetraenoic acid (20-HETE) production. This study tested whether the administration of fenofibrate would reduce blood pressure by attenuating plasma IL-6 and renal expression of cyclooxygenase-2 (COX-2), while increasing expression of renal CYP4A during 7 days of DOCA-salt hypertension. We performed uni-nephrectomy on 12–14 week old male Swiss Webster mice and implanted biotelemetry devices in control, DOCA-salt (1.5 mg/g) treated mice with or without fenofibrate (500 mg/kg/day in corn oil, intragastrically). Fenofibrate significantly decreased mean arterial pressure and plasma IL-6. In kidney homogenates, fenofibrate increased CYP4A and decreased COX-2 expression. There were no differences in renal cytochrome P450, family 2, subfamily c, polypeptide 23 (CYP2C23) and soluble expoxide hydrolase (sEH) expression between the groups. Our results suggest that the blood pressure lowering effect of PPAR-αactivation by fenofibrate involves the reduction of plasma IL-6 and COX-2, while increasing CYP4A expression during DOCA-salt hypertension. Our results may also suggest that PPAR-αactivation protects the kidney against renal injury via decreased COX-2 expression.

Evidence of peroxisomes and peroxisomal enzyme activities in the oleaginous yeast Apiotrichum curvatum

1991 ◽  
Vol 37 (5) ◽  
pp. 361-367 ◽  
Author(s):  
Wan Soo Park ◽  
Patricia A. Murphy ◽  
Bonita A. Glatz
Keyword(s):  
Enzyme Activities ◽  
Catalase Activity ◽  
Oleaginous Yeast ◽  
Corn Oil ◽  
Specific Activity ◽  
Glyoxylate Cycle ◽  
High Specific Activity ◽  
Beta Oxidation ◽  
Peroxisomal Enzyme ◽  
Apiotrichum Curvatum

The presence of peroxisomes and peroxisomal enzyme activities were investigated in the oleaginous yeast Apiotrichum curvatum ATCC 20509 (formerly Candida curvata D.) Catalase, a marker enzyme for peroxisomes, was measured in cell-free extracts prepared by sonication. The nature of the carbon and nitrogen sources in the growth medium greatly affected catalase activity. Cells grown on corn oil had high specific activity of catalase, but those grown on glucose, sucrose, or maltose had low specific activity. High specific activity of catalase was measured in cultures grown on media that supported poor growth (with soluble starch as carbon source or with methylamine, urea, or asparagine as nitrogen source). Peroxisomes from cells grown on corn oil were separated from other subcellular fractions in a discontinuous sucrose gradient. Major peaks of activity of fatty acid beta-oxidation and of two key enzymes in the glyoxylate cycle were found in fractions containing peroxisomes, but not in fractions corresponding to the mitochondria. Peroxisomal beta-oxidation showed equivalent activity with palmitoyl CoA or n-octanoyl CoA as substrate. Mitochondria did not seem to contain NAD-linked glutamate dehydrogenase. Peroxisomes with a homogeneous matrix and core surrounded by a single-layer membrane were observed with an electron microscope in cells grown on corn oil, but not in those grown on glucose. Staining with 3,3′-diaminobenzidine revealed that catalase activity was located in peroxisomes. Peroxisomes in this oleaginous yeast play important roles in lipid metabolism. Key words: lipid, peroxisomes, oleaginous, Apiotrichum curvatum, catalase, beta-oxidation, glyoxylate cycle.

scholarly journals Effects of the PPARαAgonist and Widely Used Antihyperlipidemic Drug Gemfibrozil on Hepatic Toxicity and Lipid Metabolism

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-14 ◽  
Author(s):  
Michael L. Cunningham ◽  
Bradley J. Collins ◽  
Milton R. Hejtmancik ◽  
Ronald A. Herbert ◽  
Gregory S. Travlos ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Hepatocyte Proliferation ◽  
Peroxisome Proliferator ◽  
Sprague Dawley ◽  
Peroxisome Proliferator Activated Receptor ◽  
Peroxisomal Enzyme ◽  
Expression Of Genes ◽  
B6c3f1 Mice ◽  
Liver Carcinogen ◽  
Rats And Mice

Gemfibrozil is a widely prescribed hypolipidemic agent in humans and a peroxisome proliferator and liver carcinogen in rats. Three-month feed studies of gemfibrozil were conducted by the National Toxicology Program (NTP) in male Harlan Sprague-Dawley rats, B6C3F1 mice, and Syrian hamsters, primarily to examine mechanisms of hepatocarcinogenicity. There was morphologic evidence of peroxisome proliferation in rats and mice. Increased hepatocyte proliferation was observed in rats, primarily at the earliest time point. Increases in peroxisomal enzyme activities were greatest in rats, intermediate in mice, and least in hamsters. These studies demonstrate that rats are most responsive while hamsters are least responsive. These events are causally related to hepatotoxicity and hepatocarcinogenicity of gemfibrozil in rodents via peroxisome proliferator activated receptor-α(PPARα) activation; however, there is widespread evidence that activation of PPARαin humans results in expression of genes involved in lipid metabolism, but not in hepatocellular proliferation.

Role of the peroxisome proliferator‐activated receptor in cytochrome P450 4A gene regulation

1996 ◽  
Vol 10 (11) ◽  
pp. 1241-1248 ◽  
Author(s):  
Eric F. Johnson ◽  
Colin N. A. Palmer ◽  
Keith J. Griffin ◽  
Mei‐Hui Hsu
Keyword(s):  
Gene Regulation ◽  
Cytochrome P450 ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cytochrome P450 4A

scholarly journals Prenatal Exposure to Persistent Organic Pollutants and Maternal Folic Acid Supplementation: Their Impact on Glucose Homeostasis in Male Rat Descendants

Environments ◽  
2021 ◽  
Vol 8 (3) ◽  
pp. 24
Author(s):  
Pauline Navarro ◽  
Mathieu Dalvai ◽  
Phanie L. Charest ◽  
Pauline M. Herst ◽  
Maryse Lessard ◽  
...  
Keyword(s):  
Folic Acid ◽  
Organic Pollutants ◽  
Prenatal Exposure ◽  
Glucose Homeostasis ◽  
Persistent Organic Pollutants ◽  
Corn Oil ◽  
Male Rat ◽  
Oral Glucose ◽  
Sprague Dawley ◽  
C Peptide

Exposure to persistent organic pollutants (POPs) is associated with insulin resistance while folic acid (FA) may offer a protective effect. However, the paternal contribution to metabolic phenotypes in offspring is not well known yet. Hence, we investigated whether maternal exposure to POPs affects glucose homeostasis and whether maternal FA supplementation counteracts POP effects transmitted via male descendants. Sprague–Dawley founder dams (F0) were fed a diet containing 2 or 6 mg/kg of FA and were force-fed with either a POP mixture or corn oil for 9 weeks. Subsequent male descendants did not receive any treatment. Blood glucose, plasma insulin and C-peptide were measured during an oral glucose tolerance test in males aged 90 and 180 days from generation 1 (F1), 2 (F2) and 3 (F3). Prenatal POP exposure increased fasting glucose in 90-day-old F1 males and C-peptide in 90-day-old F2 males. Prenatal FA supplementation decreased C-peptide in 90 and 180-day-old F1 males. In 180-day-old F3 males, FA supplementation counteracted POPs on fasting and postglucose C-peptide, indicating reduced insulin secretion. Prenatal exposure to an environmentally relevant POP mixture caused abnormalities in glucose homeostasis that are transmitted from one generation to the next through the paternal lineage. Prenatal FA supplementation counteracted some of the deleterious effects of POPs on glucose homeostasis.

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