Search results for "PEROXISOME"
showing 10 items of 232 documents
Anti-diabetic effects of mildronate alone or in combination with metformin in obese Zucker rats
2010
Abstract Mildronate is a cardioprotective drug, the mechanism of action of which is based on the regulation of l -carnitine concentration. We studied the metabolic effects of treatment with mildronate, metformin and a combination of the two in the Zucker rat model of obesity and impaired glucose tolerance. Zucker rats were p.o. treated daily with mildronate (200 mg/kg), metformin (300 mg/kg), and a combination of both drugs for 4 weeks. Weight gain and plasma metabolites reflecting glucose metabolism were measured. The expression of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ and target genes was measured in rat heart and liver tissues. Each treatment decreased the blood …
Natural products for the treatment of Type 2 Diabetes Mellitus
2015
Type 2 diabetes mellitus is a metabolic disease characterized by persistent hyperglycemia. High blood sugar can produce long-term complications such as cardiovascular and renal disorders, retinopathy, and poor blood flow. Its development can be prevented or delayed in people with impaired glucose tolerance by implementing lifestyle changes or the use of therapeutic agents. Some of these drugs have been obtained from plants or have a microbial origin, such as galegine isolated from Galega officinalis, which has a great similarity to the antidiabetic drug metformin. Picnogenol, acarbose, miglitol, and voglibose are other antidiabetic products of natural origin. This review compiles the princi…
Peroxisome Proliferator-Activated Receptor Deficiency Increases the Risk of Maternal Abortion and Neonatal Mortality in Murine Pregnancy with or with…
2006
We assessed the implication of peroxisome proliferator-activated receptor (PPAR) alpha deficiency in pregnancy outcome and neonatal survival and in the modulation of T cell differentiation in murine diabetic pregnancy and their offspring. Pregnant wild-type (WT) and PPAR alpha-null mice of C57BL/6J genetic background were rendered diabetic by five low doses of streptozotocin. We observed that, in the absence of diabetes, PPAR alpha deficiency resulted in an increase in abortion rate, i.e. 0% in WT mice vs. 20% in PPAR alpha-null mice [odds ratio (OR) = 14.33; P = 0.013]. Under diabetic conditions, the abortion rate was enhanced, i.e. 8.3% in WT mice vs. 50% in PPAR alpha-null mice (OR = 4.2…
CD36 as a lipid sensor
2011
International audience; CD36 is a multifunctional protein homologous to the class B scavenger receptor SR-B1 mainly found in tissues with a sustained lipid metabolism and in several hematopoieic cells. CD36 is thought to be involved in various physiological and pathological processes like angiogenesis, thrombosis, atherogenesis, Alzheimer's disease or malaria. An additive emerging function for CD36 is a role as a lipid sensor. Location of CD36 and orthologue molecules in plasma membrane of cells in contact with the external environment (e.g. gustatory, intestinal or olfactory epithelia) allows the binding of exogenous-derived ligands including dietary lipids, diglycerides from bacterial wal…
Expression of Putative Fatty Acid Transporter Genes Are Regulated by Peroxisome Proliferator-activated Receptor α and γ Activators in a Tissue- and I…
1998
Regulation of gene expression of three putative long-chain fatty acid transport proteins, fatty acid translocase (FAT), mitochondrial aspartate aminotransferase (mAspAT), and fatty acid transport protein (FATP), by drugs that activate peroxisome proliferator-activated receptor (PPAR) alpha and gamma were studied using normal and obese mice and rat hepatoma cells. FAT mRNA was induced in liver and intestine of normal mice and in hepatoma cells to various extents only by PPARalpha-activating drugs. FATP mRNA was similarly induced in liver, but to a lesser extent in intestine. The induction time course in the liver was slower for FAT and FATP mRNA than that of an mRNA encoding a peroxisomal en…
Docosahexaenoic acid modulates the expression of T-bet and GATA-3 transcription factors, independently of PPARα, through suppression of MAP kinase ac…
2009
The present study was conducted on CD4(+) T cells, isolated from wild type (WT) and PPARalpha(null) mice, in order to assess the mechanism of action of docosahexaenoic acid (DHA), an n-3 fatty acid, in the modulation of two transcription factors, i.e., T-bet and GATA-3, implicated in T-cell differentiation towards, respectively, T(H)1 and T(H)2 phenotype. The T-cells from PPARalpha(null) mice secreted higher IFN-gamma and lower IL-4 concentrations than WT T-cells. Furthermore, the deletion of PPARalpha gene in T-cells resulted in the upregulation of T-bet and downregulation of GATA-3 both at mRNA and protein levels. DHA exerted not only an inhibitory effect on T-cell proliferation, but also…
The Peroxisome Proliferator WY-14,643 Promotes Hepatocarcinogenesis Caused by Endogenously Generated Oxidative DNA Base Modifications in Repair-Defic…
2007
Abstract Basal levels of endogenously generated oxidative DNA modifications such as 7,8-dihydro-8-oxoguanine (8-oxoG) are present in apparently all mammalian cells, but their relevance for the generation of spontaneous cancers remains to be established. Both the 8-oxoG levels and the resulting spontaneous mutations are increased in the livers of Csbm/m/Ogg1−/− mice, which are deficient in the repair of 8-oxoG. In order to determine the consequences of these additional oxidative DNA modifications and mutations and thus assess the tumor initiating potency of this type of endogenous DNA damage, we treated Csbm/m/Ogg1−/− mice and repair-proficient controls with the peroxisome proliferator WY-14…
Sensitivity of liver metabolism in jerboa (Jaculus orientalis) to ciprofibrate, a peroxisome proliferator.
2009
International audience; Ciprofibrate is a well-known drug used to normalize lipid parameters and fibrinogen in atherosclerosis patients. In laboratory rodents such as rats or mice, ciprofibrate exhibits peroxisome proliferator activity. However, to date, no clear alterations or side effects caused by ciprofibrate have been noted in humans. In order to further investigate such possible relationships, we studied the effects of sustained ciprofibrate treatment in jerboas (Jaculus orientalis). In these rodents, ciprofibrate does not induce hepatomegaly or promote liver cell DNA replication, confirming that this species more closely resembles humans than do rats or mice. The jerboas were treated…
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…
Stimulation of peroxisomal palmitoyl-CoA oxidase activity by ciprofibrate in hepatic cell lines: comparative studies in Fao, MH1C1 and HepG2 cells.
1993
The response of two rat cell lines, Fao and MH1C1, and one human cell line, HepG2, to the peroxisome proliferator ciprofibrate, was studied. Using a fluorometric assay for palmitoyl-CoA oxidase, the dose- and time-dependent increase of this enzymatic activity was determined. From the lowest concentration (100 microM) stimulation is evident in the two rat cell lines. In the Fao line, the activity was stimulated reaching a seven-fold increase over the control level at 250 microM after 72 h of treatment. In the MH1C1 line, the maximum stimulation, four- to five-fold, was obtained at 250 and 500 microM after 72 h. In the HepG2 cell line, activity increased two-fold at 250 microM after 72 h reac…