Biomedical subjects

C Van den Branden

Publications and source records attributed to C Van den Branden.

At least 19 recordsLinked to original sources

PubMed2001

Altered antioxidant defence in a mouse adriamycin model of glomerulosclerosis.

BACKGROUND: Antioxidant enzyme status changes in experimental models of chronic renal disease with glomerulosclerosis. Most of the studies are performed in rats. We now investigate whether a mouse model with more rapid development of glomerulosclerosis is suitable for the study of radical-associated renal disease. METHODS: Female BALB/c mice are injected intravenously with a single dose of adriamycin (10 mg/kg). The development of glomerular and interstitial injury is evaluated by means of renal function parameters and histology. Renal cortex activities of catalase, Cu/Zn and Mn superoxide dismutase and glutathione peroxidase are measured by enzymatic techniques, and their mRNA levels by Northern blot analysis. RESULTS: The mice develop proteinuria and hypercholesterolaemia; glomerulosclerosis is present 20 days after adriamycin injection. Involvement of reactive oxygen intermediates in the disease process is supported by an increased cortex level of glutathione (1.77+/-0.13 vs 1.31+/-0.12 micromol/g kidney; P = 0.021) and ferric iron deposition in the tubulointerstitial compartment. Glomerulosclerosis and tubulointerstitial lesions are accompanied by decreased cortex activities of catalase (0.19+/-0.01 vs 0.23+/-0.01 U/mg protein; P = 0.024), glutathione peroxidase (0.28+/-0.01 vs 0.32+/-0.01 U/mg protein; P = 0.049) and Mn superoxide dismutase (6.61+/-0.91 vs 9.25+/-0.99 U/mg protein, P = 0.020). We find decreased cortex mRNA levels only for glutathione peroxidase. CONCLUSION: The fast development of glomerulosclerosis combined with an altered antioxidant status makes this mouse adriamycin model a suitable alternative for the slower rat models.

Animals↗

PubMed2000

Renal antioxidant enzymes and fibrosis-related markers in the rat adriamycin model.

Excessive generation of reactive oxygen intermediates can induce changes in the cellular antioxidant defence system. In this study we examine the antioxidant enzyme status and the expression of fibrosis-related marker proteins in the Adriamycin model of chronic renal failure in the rat. Twenty weeks after Adriamycin treatment, rats have overt nephrotic syndrome and renal failure with development of tubulo-interstitial fibrosis and glomerulosclerosis. Lipids accumulate in blood and in both glomeruli and tubulo-interstitial tissue. Desmin and alpha-smooth muscle actin expression increases in glomeruli and in the tubulo-interstitial area. Renal cortex antioxidant enzyme activities are decreased 20 weeks after Adriamycin injection (to 41% for catalase, to 56% for total superoxide dismutase and to 69% for glutathione peroxidase). The mRNA levels of catalase, Cu/Zn-superoxide dismutase and glutathione peroxidase-1 evaluated by Northern blot are decreased by more than 50% for catalase, Cu/Zn-superoxide dismutase and glutathione peroxidase-1. We conclude that in the rat Adriamycin-induced model of chronic renal failure with fibrosis, the combination of decreased antioxidant enzyme status in renal cortex with high concentrations of lipids in blood and renal tissue facilitates oxidative damage. Development of fibrosis is paralleled by increased expression of desmin and alpha-smooth muscle actin.

Animals↗

PubMed1998

Effects of Lorenzo's Oil on peroxisomes in healthy mice.

We investigated peroxisomal alterations in mice treated with different doses of Lorenzo's Oil (a therapy for X-linked adrenoleukodystrophy patients) for up to 100 days. Hepatic erucic acid levels were already significantly increased 2.2-fold and 2.6-fold in mice treated with 10% and 20% Lorenzo's Oil for 21 days, respectively. No lipidosis was found in liver, myocardium and kidney of any of the treated mice. While hepatic catalase, lauroyl-CoA oxidase and glycolate oxidase, and renal catalase activities were not induced by either diet, myocardial catalase activity was increased in most groups. This suggests that the mechanism of the effect of Lorenzo's Oil in X-linked adrenoleukodystrophy patients may not be a direct effect on the peroxisomes.

Acyl-CoA Dehydrogenase↗

PubMed1998

Morphological adaptations of human liver peroxisomes in cholestasis.

Part of the bile acid synthesis takes place in peroxisomes. An altered enterohepatic circulation of bile acids might influence peroxisomal beta-oxidation enzymes and peroxisomal morphology. We performed a morphological and morphometric investigation of peroxisomes in liver biopsy samples of eight patients with cholestasis of different origin: graft versus host reaction (n = 1), obstruction of the bile flow (n = 3), and drug-induced cholestatic hepatitis (n = 4). Peroxisomes were identified using catalase cytochemistry. They were regularly shaped and showed individual differences in electron density. A perinuclear distribution was observed in a variable number of hepatocytes in each sample. Morphometric analysis of peroxisomes revealed an increase in numerical density and surface density in all, and a decreased mean diameter in four liver samples. Based on previously obtained data in experimental animals, we hypothesize that the observed alterations in peroxisomal morphology indicate an enhanced metabolic activity of the enzymes in the peroxisomal matrix. Among them are enzymes involved in bile acid synthesis.

Adult↗

PubMed1998

Enalapril increases antioxidant enzyme activity in renal cortical tissue of five-sixths-nephrectomized rats.

In rats with five-sixths nephrectomy (remnant kidney), blood pressure, glomerulosclerosis, and proteinuria are significantly reduced by administration of the angiotensin-converting enzyme inhibitor enalapril, during 16 weeks after reduction of the nephron number. The activity of catalase in remnant-kidney cortex homogenate is not influenced by enalapril treatment; the activities of superoxide dismutase and glutathione peroxidase are significantly increased. Elevated lipid peroxidation in cortex homogenates, evaluated by malondialdehyde and 4-hydroxynonenal concentrations, is not changed by treatment. Supplementation of dietary vitamin E to enalapril treatment does not alter antioxidant enzyme activities when compared to enalapril monotherapy. These results show that enalapril improves the balance between reactive oxygen intermediates and antioxidant enzymes in the remnant-kidney cortex of the rat. This finding may in part explain the protective effect of angiotensin-converting enzyme inhibitors on the progression of glomerulosclerosis.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1998

Peroxisome-proliferating effects of fenoprofen in mice.

We report on hepatic effects obtained in vivo by treating mice with different doses of fenoprofen, an arylpropionic acid previously shown to inhibit in vitro peroxisomal very long chain fatty acid oxidation. A strong and dose-related induction of peroxisomal palmitoyl-CoA oxidase, and of carnitine acyltransferase and acyl-CoA hydrolase activities was recorded in liver homogenates of mice fed diets supplemented with different contents [0.01, 0.05, 0.1, or 1% (w/w)] of fenoprofen for 6 d. Peroxisomal glycolate oxidase and mitochondrial butyryl-CoA, octanoyl-CoA, and palmitoyl-CoA dehydrogenases were unaffected or increased. Hepatic catalase activity was significantly increased in mice fed the diet with 0.05 and 0.1% fenoprofen but, surprisingly, was not stimulated in mice fed the 1% fenoprofen-containing diet. A time-related but unequal induction of acyl-CoA oxidases and catalase was observed with the 0.1% fenoprofen diet: at 21 d of treatment, the induction of lignoceroyl-CoA and palmitoyl-CoA oxidase activities were five-fold stronger than that of catalase activity. In mice treated with 1% fenoprofen for up to 6 d, only acyl-CoA oxidase activities were found to be significantly increased. Morphometric analysis of the liver peroxisomes in mice treated with 0.1% fenoprofen evidenced an increase in size, volume density, and surface density along with a reduced ratio between perimeter and area of the peroxisomal profiles. No morphological marker for very long chain fatty acid deposition could be detected in livers from fenoprofen-treated animals. Our findings clearly demonstrate that fenoprofen acts as a peroxisome proliferator in the liver of mice and do not support the occurrence of in vivo reduction of very long chain fatty acid oxidation in liver from treated animals.

Animals↗

PubMed1997

Morphometric characteristics of peroxisomes in rats with chronic renal failure induced by five-sixth nephrectomy.

An increased H2O2 production and a decreased activity of several peroxisomal oxidases have previously been reported in kidneys of rats with five-sixth nephrectomy, a model for chronic renal failure. We investigated the morphological and morphometric characteristics of peroxisomes, the organelles in which an important part of cellular H2O2 metabolism is localized, in remnant kidneys 16 weeks after operation. The vast majority of renal peroxisomes were found in the epithelial cells of proximal tubules. The organelles were distributed throughout the cells. We observed a significant increase in size, perimeter and volume density of the peroxisomes as compared to normal kidneys. Elongated peroxisomes were less frequent. An inverse linear correlation between mean size and number of peroxisomes was found. In cortex homogenates, the activity of catalase the peroxisomal H2O2-scavenging enzyme, was significantly decreased and was inversely proportional to the mean peroxisomal diameter. The observed morphological adaptations are believed to create an unfavorable situation for the enzymatic activities in remnant kidney peroxisomes.

Adaptation, Biological↗

PubMed1997

Effect of vitamin E on antioxidant enzymes, lipid peroxidation products and glomerulosclerosis in the rat remnant kidney.

In rats with five-sixth nephrectomy (remnant kidney), glomerulosclerosis was significantly reduced by dietary administration of vitamin E (alpha-tocopherol) during 11 and 16 weeks after reduction of nephron number. The activity of catalase and the production of H2O2 in remnant kidney cortex homogenate were not influenced by the vitamin E diet; however, the activities of glutathione peroxidase and superoxide dismutase were significantly increased (up to 140 and 180%, respectively, after 16 weeks). Lipid peroxidation, evaluated by malonaldehyde and 4-hydroxynonenal concentrations, was decreased in cortex homogenates and in urine. Though the extent of the effect of vitamin E on antioxidant enzyme levels and lipid peroxidation is small, the important reduction of glomerulosclerosis is in favor of dietary supplementation with vitamin E.

Animals↗

PubMed1997

Carvedilol protects against glomerulosclerosis in rat remnant kidney without general changes in antioxidant enzyme status. A comparative study of two beta-blocking drugs, carvedilol and propanolol.

Nephron loss leads to increased production of reactive oxygen intermediates. We measured the effect of carvedilol, a beta-blocking drug with radical scavenging properties, on renal function, glomerulosclerosis, antioxidant enzyme status and in vivo hydrogen peroxide (H2O2) production in rats with chronic renal failure caused by 5/6 nephrectomy (remnant kidney) and compared results to data obtained with propranolol, a beta-blocking drug without scavenging characteristics. Carvedilol and propranolol were administered during 11 weeks following reduction of nephron number. Kidneys were examined using enzymatic and histological techniques. Both carvedilol and propranolol decreased systolic blood pressure. Compared to propranolol, carvedilol offered some additional beneficial effects on renal function, particularly with regard to glomerulosclerosis. Lipid peroxidation, evaluated by malonaldehyde and 4-hydroxynonenal concentration in cortex homogenates, was decreased in carvedilol-treated rats only. Superior beneficial effect of carvedilol treatment is not linked to a significant up-regulation of the activities of the remnant kidney antioxidant enzymes (catalase, glutathione peroxidase and superoxide dismutase) or to a decreased in vivo H2O2 production.

Adrenergic beta-Antagonists↗

PubMed1996

Dietary docosahexaenoic acid has little effect on peroxisomes in healthy mice.

NMRI mice were fed diets supplemented with 0.05, 0.2, or 2% (w/w) docosahexaenoic acid (DHA), a polyunsaturated fatty acid present in fish oil, for 3 d, 3 wk, or 3 mon. The doses of DHA were chosen to supply the mice with concentrations of DHA which approximate those that have been reported to be beneficial to patients with peroxisomal disease. Diets containing 0.05 or 0.2% DHA did not change hepatic, myocardial, and renal catalase (EC 1.11.1.6) activity except for a slight but significant increase (to 120%) in myocardial catalase activity in mice treated with the 0.05% DHA diet for 3 mon. A diet with 2% DHA induced myocardial catalase activity to 150% after both 3 d and 3 wk of administration. In the liver of mice fed this diet for 3 wk, hepatic catalase activity was increased to 140% while no induction of palmitoyl-CoA oxidase (EC 1.3.99.3), urate oxidase (EC 1.7.3.3), and L-alpha-hydroxyisovalerate oxidase (EC 1.1.3.a) was observed. With the light microscope, no changes in peroxisomal morphology were visually evaluated in catalase stained sections of liver, myocardium, and kidney of mice fed either diet. Our results show that in healthy mice a low dietary DHA dose (< 0.2%; this corresponds to a dose prescribed to peroxisomal patients) has no effect on several hepatic peroxisomal H2O2-producing enzymes, including the rate-limiting enzyme of the peroxisomal fatty acid beta-oxidation. This may indicate that such a DHA dose will not add a strong load on the often disturbed fatty acid metabolism in the liver of patients with peroxisomal disorders.

Acyl-CoA Oxidase↗

PubMed1996

Morphometric characteristics of human hepatocellular peroxisomes in alcoholic liver disease.

Hepatocellular peroxisomes harbor one of the metabolic pathways for ethanol metabolism (i.e., catalase in the presence of H2O2-generating enzymes). We studied the morphometric characteristics of these organelles in 26 biopsy samples of patients with different alcohol-induced lesions (12 with steatosis, 5 with hepatitis, and 9 with cirrhosis) and compared the findings with those obtained in seven control livers. All 33 human liver biopsy samples were stained for catalase activity to facilitate peroxisomal identification. Morphometric analysis of the peroxisomes was performed on calibrated electron micrographs. The numerical density of the peroxisomes was significantly increased to 183%, whereas the mean peroxisomal diameter (dcircle) revealed a significant decrease to 89%. This resulted in a normal volume density of the peroxisomal compartment, whereas the surface density was significantly induced. Peroxisomal shape was not different between alcoholic and control livers. When alcoholic livers were divided into three subgroups according to histopathological findings, similar morphometric results were obtained when compared with control livers, although significantly was sometimes lost. No differences in peroxisomal characteristics were found among alcoholic subgroups. The mean peroxisomal diameter per human liver (alcoholic and control) was inversely correlated to the numerical density. It is concluded that the peroxisomal adaptation in human alcoholic liver is such as to create an efficient environment for a presumably increased peroxisomal metabolism.

Adult↗

PubMed1995

Alterations of peroxisomes in steatosis of the human liver: a quantitative study.

We investigated the hepatocellular peroxisomes in 27 patients with steatosis of the liver by means of catalase cytochemistry, light and electron microscopic study, and morphometry. Seven normal human livers were used as controls. In our patients, fatty liver was mainly associated with alcohol abuse or obesity. Indications for a slight decrease in catalase activity and for a proliferation were found in visual evaluation of the peroxisomes. Morphometric analysis showed a significant decrease in mean peroxisomal diameter (to 87%) and a simultaneous significant elevation to numerical density of the peroxisomes (to 188%); this resulted in a normal volume density and a significant increase to (133%) in surface density. However, individual differences were found. No differences in peroxisomal characteristics were found between fatty livers of different causes. A significant inverse linear correlation between mean peroxisomal diameter and numerical density was found in patients with fatty livers. Because a similar correlation was also found when control data were added to the fatty liver data, we hypothesize that the peroxisomal compartment in human fatty livers is adapted in such a way to permit the same metabolic efficiency as in control livers.

Adult↗

PubMed1995

Peroxisomes in mice fed a diet supplemented with low doses of fish oil.

The influence of low dietary doses (0.1 and 0.8% w/w) of a commercial fish oil preparation on peroxisomes in normal mice was studied and compared to the known strong inductive effects of high (10%) fish oil diets. Low fish oil doses were chosen to supply the mice with a concentration of docosahexaenoic acid, which was beneficial to patients with a peroxisomal disease. Peroxisomes were evaluated by cytochemical, morphometric, and enzymological techniques. The 0.1% fish oil diet had no effect on peroxisomes in liver, heart, and kidney even after prolonged treatment. The 0.8% diet did not change the peroxisomal number nor the catalase (EC 1.11.1.6) activity in the liver. Hepatic peroxisomal beta-oxidation, however, was increased by 50% after 14 d. This was accompanied by reduced peroxisomal size. The 0.8% diet also caused a small increase (+25%) in myocardial catalase activity. No effect was observed in kidneys. Our results indicate that in mice a low (< 0.8%) dietary fish oil dose has no or only a slight effect on hepatic peroxisomal beta-oxidation. This may be of particular interest to patients with a peroxisomal fatty acid beta-oxidation defect and who display a severe deficiency of docosahexaenoic acid--diets supplemented with low fish oil doses will improve the docosahexaenoic acid level without adding a strong load to the disturbed fatty acid metabolism.

Animals↗

PubMed1994

Peroxisomes in liver, heart, and kidney of mice fed a commercial fish oil preparation: original data and review on peroxisomal changes induced by high-fat diets.

Male NMRI mice were fed a diet with 10% w/w Beromegan for up to three weeks. Beromegan is a commercial fish (salmon) oil preparation rich in eicosapentaenoic acid and docosahexaenoic acid. Peroxisomal beta-oxidation capacity, catalase activity, and ultrastructural morphometry of the hepatic peroxisomes were investigated. In myocardium and kidney, catalase activity, peroxisomal staining after catalase cytochemistry, peroxisomal morphology, and morphometry (in myocardium) were evaluated. In liver, we found a significant increase in peroxisomal beta-oxidation, catalase activity, and peroxisomal number already after 3 days of dietary treatment. These changes were more pronounced after 3 weeks. Peroxisomal size was not changed. Positive correlations were found between peroxisomal enzyme activities and the number but not the size of the peroxisomes, and between catalase activity and beta-oxidation capacity. The mean peroxisomal diameter per animal was inversely proportional to catalase activity measured in homogenate. In myocardium, catalase activity was increased with duration of fish oil feeding. Peroxisomal staining, number, and size were also increased when compared to controls. In kidney, no alterations were observed. Our results indicate a beneficial effect of a diet supplemented with fish oil on the peroxisomal metabolism in liver and myocardium; it differs from the changes induced by xenobiotic peroxisome proliferation.

Animals↗

PubMed1993

Peroxisomes in liver, kidney and duodenum of nude mice bearing xenografts of human pancreatic adenocarcinomas.

In the liver, kidney and duodenum of nude mice with xenografts of two human pancreatic adenocarcinomas differing in growth rate, catalase activity was assayed and peroxisomes were studied using catalase cytochemistry and light and electron microscopy. Hepatic and duodenal catalase activity were significantly decreased in tumour-bearing mice. Renal catalase activity was unchanged. At light microscopic level, a decrease in peroxisomal staining was evident in all duodenums and most livers of tumour-bearing mice. Only minor changes were observed in the kidneys. Ultrastructural morphometry of the hepatocellular peroxisomes revealed a decrease in size, volume density and surface density only in mice with fast-growing xenografts. These observations indicate that the two pancreatic adenocarcinomas exerted a different effect on the hepatic peroxisomes, and that catalase activity and peroxisomes in liver and duodenum are more affected than in kidney.

Adenocarcinoma↗

PubMed1993

Altered adrenocortical response under the influence of experimentally increased serum very long chain fatty acids in rats.

C 26:0/C 22:0 ratio can be experimentally increased in serum of normal rats by oral administration of hexacosanoic acid (C 26:0) or of thioridazine, an inhibitor of peroxisomal beta-oxidation. This causes a decreased corticosterone response as well as decreased mobilization of cholesterol esters in zona fasciculata interna cells following ACTH administration. Zona fasciculata interna cells and their nuclei are enlarged and contain more Feulgen DNA in thioridazine-fed rats. The similarity of adrenocortical response to inhibition of peroxisomal beta-oxidation and to C 26:0 administration points to raised VLCFA as the common factor which is also operative in many peroxisomal diseases accompanied by adrenocortical function defects.

Adrenal Glands↗

PubMed1990

Experimental inhibition of peroxisomal beta-oxidation in rats: influence on brain myelination.

Oral administration of thioridazine, an inhibitor of peroxisomal beta-oxidation, to normal rats from weaning till day 60 causes a small increase of the very long chain fatty acid C26 in brain lipids. Myelination in the brain is decreased. In the genu of the corpus callosum the ratio of non-myelinated/myelinated axons is increased. In the commissura anterior the myelin sheaths of the axons are significantly thinner in treated than in control animals. Undernourishment caused by the drug is minimal in this experiment. Area and total DNA of glial nuclei are unaltered in both the genu and the commissura anterior of treated rats. The distribution of chromatin (texture), however, shows small differences in the corpus callosum.

Animals↗

PubMed1989

Inhibition of peroxisomal beta-oxidation and brain development in rats.

Thioridazine, an inhibitor of peroxisomal beta-oxidation, was administered orally to nursing rats during the period of maximal myelination in the pups (8-21 days postnatally). Under the experimental conditions, thioridazine causes accumulation of C24 and C26 fatty acids in pup brain lipids, an effect we consider to be a typical consequence of inhibited peroxisomal beta-oxidation. In the corpus callosum of treated pups, the relationship between axon diameter and myelin sheath thickness is altered compared with matched controls. Thioridazine also induces undernourishment effects in 21 day-old rats. Body and brain weight are severely reduced. Liver peroxisomes show a starvation-type metabolism. Undernourishment is known to influence myelination in developing rat brain. However, known consequences of undernourishment, such as decreased myelin concentration in whole brain, decreased percentage of myelinated fibers, and decreased granule-to-Purkinje cell ratio are not present.

Animals↗