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ABSTRACT: Weanling rats fed a choline-deficient diet develop kidney oxidative damage, tubular and cortical kidney necrosis, renal failure and animal death. The effect of dietary menhaden oil was assayed on the mentioned sequence correlating oxidative stress with renal structure and function. Rats were fed ad libitum 4 different diets: (a) a choline-deficient diet with corn oil and sunflower hydrogenated oil as a source of fatty acids; (b) the same diet supplemented with choline; (c) a choline-deficient diet with menhaden oil as a source of fatty acids; and (d) the previous diet supplemented with choline. Animals were sacrificed at days 0, 2, 4 and 7. The histopathological study of the kidneys showed that renal necrosis was only observed at day 7 in choline-deficient rats receiving the vegetable oil diet, simultaneously with increased creatinine plasma levels. Homogenate chemiluminescence (BOOH-initiated chemiluminescence) and phospholipid oxidation indicate the development of oxidative stress and damage in choline-deficient rats fed vegetable oils as well as the protective effect of menhaden oil. Rats fed with the fish oil diet showed that oxidative stress and damage develop later, as compared with vegetable oil, with no morphological damage during the experimental period.
Food & function. 12/2012;
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ABSTRACT: Weanling Sprague-Dawley rats were fed on a choline-deficient diet with hydrogenated vegetable oil and corn oil as lipids develop acute renal failure. Pathogenesis of the latter is controversial and an ischemic mechanism has been proposed. Arachidonic acid derivatives are involved in the regulation of vascular tonus. Vasospasm could be due to an increase in tromboxane A2-mediated vasoconstriction or to a decrease in prostacyclin-induced vasodilatation. Enzymes involved in the synthesis of both compounds are tromboxane A2- and prostacyclin-synthase respectively. The aim of this study was to identify the variable number tandem repeats (VNTR) in the promoter region of prostacyclin synthase gene and verify if there exists a relationship between the occurrence of VNTR in those choline-deficient rats which die because of acute renal failure and those which do not. We verified the presence of the VNTR in the prostacyclin synthase rat gene, but we did not find any difference in the molecular weight of the alleles between experimental and control rats. Renal reparation of the acute kidney injury due to choline deficiency in some rats is not related with differences in VNTR in the promoter region of the prostacyclin synthase gene.
Biocell: official journal of the Sociedades Latinoamericanas de Microscopía Electronica ... et. al 08/2010; 34(2):65-70. · 0.63 Impact Factor
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ABSTRACT: Some aspects of the functional, morphological, and morphometrical characteristics of chronic progressive nephropathy occurring in 18- to 26-month-old male rats and in 3-month-old control rats were studied. Rats with chronic progressive nephropathy were proteinuric and showed a slight increase in serum creatinine and no changes in blood pressure. The morphological changes were studied by light microscopy, high-resolution light microscopy, and electron microscopy. They showed focal and segmental or global glomerulosclerosis, the three types of atrophic tubules ("classic," "thyroid-like," and "endocrine") described by Nadasdy et al, as well as interstitial fibrosis with mononuclear cell infiltrates. On certain occasions, small vessels showed hyalinosis. Glomerular morphometrical studies showed a biphasic pattern in the glomeruli progressing toward obsolescence. Vascular morphometrical studies showed significant increase in media wall thickness and media cross-sectional area in the 18- to 26-month-old rats. These results support the hypothesis that changes in the vascular system are not of utmost importance in the pathogenesis of chronic progressive nephropathy, and that glomerular sequential changes seem to be of paramount significance in the progression of the disease.
Renal Failure 01/2010; 32(1):112-8. · 0.82 Impact Factor
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ABSTRACT: Oxidative stress and damage are characterized by decreased tissue antioxidant levels, consumption of tissue alpha-tocopherol, and increased lipid peroxidation. These processes occur earlier than necrosis in the liver, heart, kidney, and brain of weanling rats fed a choline deficient (CD) diet. In tissues, water-soluble antioxidants were analyzed as total reactive antioxidant potential (TRAP), alpha-tocopherol content was estimated from homogenate chemiluminescence (homogenate-CL), and lipid peroxidation was evaluated by thiobarbituric acid reactive substances (TBARS). Histopathology showed hepatic steatosis at days 1-7, tubular and glomerular necrosis in kidney at days 6 and 7, and inflammation and necrosis in heart at days 6 and 7. TRAP levels decreased by 18%, 48%, 56%, and 66% at day 7, with t(1/2) (times for half maximal change) of 2.0, 1.8, 2.5, and 3.0 days in liver, kidney, heart, and brain, respectively. Homogenate-CL increased by 97%, 113%, 18%, and 297% at day 7, with t(1/2) of 2.5, 2.6, 2.8, and 3.2 days in the four organs, respectively. TBARS contents increased by 98%, 157%, 104%, and 347% at day 7, with t(1/2) of 2.6, 2.8, 3.0, and 5.0 days in the four organs, respectively. Plasma showed a 33% decrease in TRAP and a 5-fold increase in TBARS at day 5. Oxidative stress and damage are processes occurring earlier than necrosis in the kidney and heart. In case of steatosis prior to antioxidant consumption and increased lipid peroxidation, no necrosis is observed in the liver.
Experimental and Molecular Pathology 11/2009; 88(1):143-9. · 2.42 Impact Factor
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ABSTRACT: The aim of the present study is to evaluate the effects of intraosseous implantation of silica-based bioactive glass (BG) particles on rat kidney under experimental renal failure. The animals are assigned to one of the two groups: renal failure (RF) and renal failure + bioactive glass (RF + BG). Particles of melt-derived 45S5 BG are implanted in the marrow of one tibia of each animal in the RF + BG group. The animals are killed 24 h and 14 days postimplantation. The RF + BG group exhibits a statistically significant increase in serum urea 24 h postimplantation. The tibiae of the RF + BG group are resected and embedded in methyl-methacrylate resin. Ground sections are analyzed by light microscopy and energy-dispersive X-ray (EDX) analysis. The presence of silicon, calcium, and phosphorus is evaluated in the BG particles. A 55% reduction in silicon content is observed at 14 days postimplantation as compared with that at 24 h.Light microscopy analysis reveals lesions in kidney parenchyma. Hyperplasia associated with nuclear vacuolization in the tubules and a marked thickening of the basal membrane are observed in the renal cortex of the RF + BG animals killed at 24 h postimplantation, but not in those at 14 days. The present results demonstrate reversible renal cell injury in rats exposed to intraosseous implantation of silica-based BG particles under experimental RF.
Journal of Biomaterials Applications 05/2007; 21(4):431-42. · 2.08 Impact Factor
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ABSTRACT: Previous studies have shown ocular haemorrhages in choline-deficient rats. The aim of this paper is to study further the relationship between ocular and renal lesions and biochemical alterations in rats fed a choline-deficient diet. Fifty one weanling male Wistar rats, were divided into two groups. Thirty one of them were fed a choline-deficient diet and the rest was fed a choline-supplemented diet ad libitum. Animals from both groups were killed between the fifth and the eighth day. Urea, creatinine and homocysteine concentrations in blood were determined. Eyes were used for light microscopy study; high resolution light microscopy and the study of the retina as "rétine a plat". Kidneys were studied by light microscopy. Choline-supplemented rats did not show ocular or renal lesion. Choline-deficient rats that showed renal lesions, tubular or cortical necrosis, did not always have ocular changes. There were no ocular changes in the only choline-deficient rat without renal lesion. The ocular changes consisted mainly in haemorrhage in both cameras and ciliary and vitreous bodies. Correlations between ocular and renal lesion (r = 0.72, p < 0.0001, CI 95%: 0.48-0.86); ocular lesion and creatinine (r = 0.86, p < 0.0001, Cl 95%: 0.72-0.93) and ocular lesion and urea (r = 0.70, p < 0.0001, Cl 95%: 0.44-0.85) were positive. Choline-deficiency induces ocular haemorrhagic lesions after the development of renal necrosis. The ocular pathology could be due to the immaturity of the ocular vasculature at this age. The hyaloid, choroid and retinal system are involved.
Medicina 01/2006; 66(5):415-20. · 0.47 Impact Factor
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ABSTRACT: Hyperhomocysteinemia is able to promote glomerular damage and generate tubulointerstitial lesions. These findings were reported in rats with unilateral nephrectomy or in weanling rats with normal function, two experimental models that are exposed to other concomitant vascular risk factors. The aim of this work is to study whether mild hyperhomocisteinemia per se can induce renal histopathologic changes in adults rats with normal renal function at either 10 or 44 weeks of hyperhomocysteinemia.
Two months old male Wistar rats (N= 52) were randomly allocated to either a normal control (N= 26) or hyperhomocysteinemic (N= 26) group. Control and hyperhomocysteinemic groups had free access to either tap water or homocysteine thiolactone 50 mg/kg/day, during 10 or 44 weeks. Plasma homocysteine levels were determined by a high-performance liquid chromatography (HPLC) method. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were calculated from inulin and sodium para-aminohippurate (PAH) clearance determinations. Structural renal changes were investigated in kidneys fixed by perfusion. Histopathologic and morphometric analysis were carried out by standard methods.
Plasma total homocysteine levels were 53% (10 weeks) and 56% (44 weeks) higher in hyperhomocysteinemic group compared to the control group. GFR and RPF were significantly lower in hyperhomocysteinemic than in control group. The histopathologic and morphometric studies did not show any differences between the control and hyperhomocysteinemic rats at 10 or 44 weeks.
The present results show that mild hyperhomocysteinemia is able to induce renal functional and biochemical alterations in male adult rats that are not associated with renal histopathologic changes.
Kidney International 12/2004; 66(5):1866-72. · 6.61 Impact Factor
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ABSTRACT: Little is known at present about the saccharide components of lipofuscin (age pigment) and ceroid pigments in situ. The purpose of this study was, therefore, to study in detail the lectin reactivities of lipofuscin in neurons and cardiac myocytes of old humans and rats. In addition, those of diverse ceroid pigments found in human aortic atheromas, in the livers of choline-deficient rats, in the uteri of vitamin E-deficient rats and in the crushed epididymal fat pad of rats, are included. Cryostat and deparaffinized sections from all these tissues were either extracted with a solvent mixture of chloroformmethanol-water (10103, v/v) and incubated with 7 different biotinylated lectins or left untreated. Delipidation was done in order to study whether it was possible to discriminate between the saccharide moieties of glycolipids and glycoproteins of lipofuscin and ceroid pigments in situ. Other similarly treated sections were used to study the autofluorescence, sudanophilia, acid-fastness and reactivity to PAS. The frequency and intensity of lectin binding and standard histochemical properties of all the pigments were evaluated semi-quantitatively and blind. The results indicated that mannose was in general the most consistently detected sugar residue in lipofuscin granules of humans and rats, and that this pigment may also contain acetylglucosamine, acetylgalactosamine, sialic acid, galactose and fucose. However, notable differences were found not only in the lipofuscin saccharide components of different cell types of humans and rats, but also in those in the same type of cells in both species. Although mannose was not detected in the hepatic ceroid of choline-deficient rats, this saccharide moiety was almost always present in the other ceroid pigments. Each of the ceroids also contained other types of saccharides although the frequency of the latter varied between different ceroid pigments. While lipofuscin and each of the ceroid pigments showed somewhat different lectin binding patterns, the variability in the frequency of reactivity to lectins suggests that these patterns may not be permanent but transient. In this sense, it appears that lectin histochemistry may not allow these pigments to be differentiated. Furthermore, the extractive procedures used in this study did not enable us to determine whether the saccharides detected in the pigments in situ corresponded to glycolipids or glycoproteins.
Histochemie 05/1995; 103(6):435-445. · 2.59 Impact Factor
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ABSTRACT: Although it has been shown that the administration of estrogen to rats is associated with renal pigmentation, neither the nature nor the precise ultrastructural location of the pigment have been yet established.Sequential histochemical and electron microscopic studies carried out in kidneys of Wistar female rats injected intramuscularly with estradiol at various intervals during 7 months, indicated that the pigment accumulating in the epithelium of proximal convoluted tubules fundamentally consisted of hemosiderin, although some other constituents appear to be also present. The pigment deposits were located within lysosomes that with time became post-lysosomes. These deposits differ from those of lipofuscin or ceroid pigments. The possible functional implications of this estrogenassociated hemosiderin pigment remain unknown.
Experimental and Molecular Pathology.
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ABSTRACT: The persistent indiscriminate use of the term lipofuscin for the pigments encountered in pathological conditions, and which should be most properly termed ceroid pigments, is still creating unnecessary conceptual and nomenclature problems, and a great deal of confusion. While both the age-dependent lipofuscin and the pathologically formed ceroid pigments have somewhat similar physical and histochemical properties, sufficient differences to properly identify these two types of pigments are presented in this communication. In addition, because little is known on the saccharide components of lipofuscin and ceroid pigments in situ, we have in recent years explored the lectin binding characteristics of lipofuscin in human and rats, as well as in diverse ceroid pigments experimentally induced in rats. Our lectin histochemical results showed qualitative and quantitative differences in the saccharide composition between human cerebral neurolipofuscin and the intra and extracellular ceroid pigment of human atheromas, as well as, between rat lipofuscin and the ceroid pigments induced in these animals.
Archives of Gerontology and Geriatrics 34(3):193-203. · 1.45 Impact Factor
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ABSTRACT: The typical and most consistent physico-histochemical properties of lipofuscin granules, such as autofluorescence, sudanophilia, acid-fastness, PAS-reactivity, and lectin reactivities for diverse saccharide moieties have been generally detected in tissue specimens of old humans and animals. The purpose of this study was, therefore, to explore possible sequential variations of each of these properties in cortical neurons of the left cerebral temporo-parietal areas from individuals dying from the first to the ninth decade. Autofluorescence was studied with an ad hoc equipped microscope, sudanophilia was evaluated by Oil-red-O (ORO) staining, acid-fastness by long Ziehl-Nielsen reagent, PAS reactivity by the periodic-acid-Schiff reagent before and after diastase treatment, and the saccharide moieties by the use of a commercial kit of seven different biotinylated lectins. In the specimen from a 5-year-old child, lipofuscin granules were detected in less than 5% of the cortical neurons, but these granules already showed golden-yellow autofluorescence, sudanophilia, acid-fastness and PAS-reactivity. From the second to the ninth decade of life, perikaryal lipofuscin granules were found in practically all cortical neurons with apparent agewise increases in the intensity of sudanophilia and PAS-reactivity, but with variable acid-fastness expression. Surprisingly, however, no saccharide residues were detected by lectin histochemistry before the fifth decade of life. First detected saccharide was mannose in specimens from the fifth decade of life, and at later decades acetyl galactosamine, sialic acid and lactose were also found. Although, the reasons for the absence of lipofuscin affinity for the seven lectins used in this study in the cortical neurons of young and middle-aged individuals are presently unknown, these unexpected findings suggested important evolutionary changes of biogenesis and composition of the age-pigment.
Archives of Gerontology and Geriatrics 34(3):219-31. · 1.45 Impact Factor
