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J Pedraza-Chaverri

Publications and source records attributed to J Pedraza-Chaverri.

At least 19 recordsLinked to original sources
PubMed2001

Comparative analysis of superoxide dismutase activity between acute pharmacological models and a transgenic mouse model of Huntington's disease.

We examined the activity of striatal superoxide dismutase (SOD) in two acute pharmacological models of Huntington's disease (HD), and compared it with SOD activity in the striata of mice transgenic for the HD mutation. Total SOD, and Cu/ZnSOD activities increased in young transgenic mice, but decreased in older (35 week) mice. We consider that the increased enzyme activity represents a compensatory mechanism to protect cells from free radical-induced damage, but the system becomes insufficient in older animals. Major decreases in SOD activity were also observed both after quinolinic acid and 3-nitropropionic acid intrastriatal injections. The present results indicate that in both types of HD models striatal oxidative damage occurs, and that it is associated with alterations in the cellular antioxidant system.

Animals↗
PubMed2000

Hepatic histidase and muscle branched chain aminotransferase gene expression in experimental nephrosis.

Protein and amino acid metabolism is altered during nephrotic syndrome. However, the expression of the amino acid degrading enzymes has not been well studied. The objective of this work was to assess the expression of hepatic histidase (Hal) and skeletal muscle mitochondrial branched chain amino transferase (BCATm) in rats with experimental nephrotic syndrome induced by a single injection of puromycin aminonucleoside (150 mg/kg). Six days after the injection rats were killed and hepatic Hal and skeletal muscle BCATm activities were measured. Also, total mRNA from both tissues was isolated and Hal and BCATm mRNA expression were analyzed by Northern blot. Rats with NS showed a reduction in food intake with respect to the control group. Hepatic Hal activity increased significantly in nephrotic and pair fed rats by 59% compared to control group. This change in activity was associated with a corresponding increase in Hal mRNA abundance. On the other hand, skeletal muscle BCATm activity and mRNA abundance were similar in the three groups studied. These results suggest that the increase in Hal expression was associated with the reduced food intake and not to the NS. However, BCAT expression did not change indicating the importance of BCAA in body nitrogen conservation.

Animals↗
PubMed1999

Effect of the in vivo catalase inhibition on aminonucleoside nephrosis.

Reactive oxygen species have been involved in the pathophysiology of puromycin aminonucleoside (PAN)-nephrosis. The role of H2O2 in these rats may be studied modulating the amount or activity of catalase, which breakdowns H2O2 to water and oxygen. To explore the role of H2O2 in this experimental model, we studied the effect of the in vivo catalase inhibiton with 3-amino-1,2,4-triazole (ATZ) on the course of PAN-nephrosis. Four groups of rats were studied: control rats (CT group), PAN-injected rats (PAN group), ATZ-injected rats (ATZ group), and ATZ- and PAN-injected rats (ATZPAN group). Rats were placed in metabolic cages to collect 24 h urine along the study, ATZ (1 g/kg) was given 24 h before PAN injection (75 mg/kg), and the proteinuria was measured on days 0, 2, 4, 6, 8, and 10. Proteinuria started before (day 4) and was significantly higher on days 6, 8, and 10 in the ATZPAN group than in the PAN group. On day 10, hypercholesterolemia was significantly higher in the ATZPAN group than in the PAN group. These data indicate that the in vivo catalase inhibition magnifies PAN-nephrosis, suggesting that H2O2 is produced in vivo and involved in the renal damage in this experimental disease.

Amitrole↗
PubMed1998

Induction of clusterin in tubules of nephrotic rats.

Clusterin is a glycoprotein induced after renal tubular cell injury. The purpose of this study was to examine the expression of clusterin in a disease model characterized early in its course by predominant glomerular injury. Male Wistar rats (weighing 251 +/- 16 g) were treated with puromycin aminonucleoside (PAN: 15 mg/100 g body wt, subcutaneously; n = 7) or vehicle (control; n = 8). The kidneys were harvested 6 d after treatment, when rats were nephrotic. Clusterin mRNA was markedly induced in the kidneys of nephrotic rats (8.5-fold versus control). Immunohistochemistry studies demonstrated clusterin primarily in tubules in the cortex and medulla. Many of the tubules staining for clusterin were dilated but had no other differentiating morphologic features. Increased numbers of proliferating tubular cells were seen at 6 d, but there was no correlation between these cells and clusterin staining. In contrast to the extent and pattern of clusterin staining, vimentin was seen in only sporadic, dilated tubules, in addition to its expected glomerular localization. An increase in clusterin mRNA was not seen 1, 2, or 4 d after PAN injection. In conclusion, tubular epithelial cell induction of clusterin occurs in the kidneys of nephrotic rats. The appearance of clusterin precedes the development of tubulointerstitial disease and may be a response to the proteinuria.

Animals↗
PubMed1997

Reduced kidney branched chain aminotransferase expression in puromycin aminonucleoside-induced nephrotic syndrome.

Injection of puromycin aminonucleoside to rats induces nephrotic syndrome characterized by hypoalbuminemia, proteinuria and hypercholesterolemia. In these rats, a low protein diet (6% casein diet) increased serum albumin by 26.3%, decreased proteinuria by 39% and reduced total cholesterol by 32%. Branched chain aminotransferase activity in kidney mitochondria of nephrotic rats fed 20 or 6% casein diet decreased by 30 and 24% with respect to their pair-fed groups and it was not modified by the protein content of the diet. Mitochondrial branched chain aminotransferase mRNA expression decreased by 67.3 and 72.5% in nephrotic rats fed 20 and 6% casein diet in comparison to their pair-fed groups. Total serum branched chain amino acids concentration (leucine, isoleucine, valine) in nephrotic rats was 30% higher than their pair-fed groups and it was associated with a decrease in the branched chain aminotransferase activity and mRNA expression suggesting that the catabolism of branched chain amino acid is reduced to conserve body nitrogen.

Animals↗
PubMed1995

Effect of dietary antioxidants on puromycin aminonucleoside nephrotic syndrome.

Several studies indicate the pathophysiological importance of reactive oxygen species in rats with nephrotic syndrome induced by puromycin aminonucleoside, an experimental model of the human minimal change disease. The role of reactive oxygen species in these rats was further evaluated, examining the effect of dietary deficiency and supplementation of antioxidants (vitamin E and selenium) on biochemical and renal ultrastructural alterations induced by puromycin aminonucleoside. Male Wistar rats, weaned at 3 weeks, were placed on diets normal, deficient or supplemented in vitamin E and selenium for 4 weeks. At the end of this period, rats were divided in two groups: control (sacrificed without any further treatment) and nephrotic (injected with puromycin aminonucleoside and sacrificed 7 and 22 days later). In control rats, the dietary deficiency or supplementation of antioxidants resulted in no significative differences in renal function, proteinuria or kidney ultrastructure. However, kidney lipoperoxidation, kidney glutathione peroxidase activity and circulating levels of vitamin E changed according to the amount of antioxidants in the diet. Seven days after the injection of puromycin aminonucleoside, rats fed normal, deficient or supplemented diets, developed nephrotic syndrome. However, proteinuria, hypoproteinemia, renal dysfunction and ultrastructural alterations were higher in rats fed a deficient diet. In contrast, proteinuria and kidney ultrastructural alterations were lower in rats fed a supplemented diet. Kidney lipoperoxidation and glutathione peroxidase activity increased on day 7 in rats fed a normal or a deficient diet, but not in rats fed a supplemented diet. This study shows that nephrotic syndrome induced by puromycin aminonucleoside in rats is modified by dietary antioxidants (vitamin E and selenium). Dietary supplementation ameliorates it and dietary deficiency exacerbates it.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Histological and subcellular distribution of 65 and 70 kD heat shock proteins in experimental nephrotoxic injury.

The cellular distribution of 65 and 70 kD heat shock proteins (HSPs) was studied in the normal rat kidney and after acute tubular necrosis (ATN) induced by inorganic mercury (HgCl2). In the normal kidney the 65 kD HSP was found in the cytoplasm of podocytes and proximal convoluted tubules, whereas the 70 kD HSP was located in nuclei and cytoplasm of podocytes, cortical convoluted, and collecting tubules. The distribution of both HSPs along ATN changed as a function of time. In the early phase, before evidence of histological damage, both HSPs were found in the pielocaly ceal epithelium and medullary collecting tubules. During the necrotic phase, HSPs coexisted with sites of severe damage (i.e. cortical tubules). With immunoelectron microscopy damaged cells showed an abundance of 65 kD HSP-I in mitochondria, as well as in chromatin and nucleoli, while 70 kD HSP-I was overexpressed in the cytoplasm, mito chondria, lysosomes, cytoskeleton, chromatin, and nucleoli, and coincided with urinary excretion of HSPs. In the postregenerative phase, the distribution of HSPs was similar to that found in the normal kidney. HSPs of 65 and 70 kD were encountered constitutionally and their immunolabeling is correlated with the magnitude of cell injury.

Animals↗
PubMed1995

Pituitary-ovarian dysfunction in rats with induced nephrotic syndrome.

The reproductive hormonal profile was evaluated in female rats with experimental nephrotic syndrome induced with a single subcutaneous dose of puromycin aminonucleoside (PAN). Serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone (P4), testosterone and 17 beta-estradiol (E2) were determined sequentially in control and experimental groups on days 1, 3, 7 and 10 after PAN administration. Prolactin levels were also assessed on day 10. In both groups, vaginal smears were taken daily throughout the study to evaluate cyclic histological changes. At the end of the experiment the histological appearance of the ovaries was evaluated by light microscopy. Nephrotic rats had a rapid loss of the estrous cycle starting on day 4, which set them at diestrus. At the same time the hormonal evaluation indicated a gradual decrease in E2, LH and P4 concentrations, starting from days 3, 7 and 10, respectively. No significant changes were noted in FSH or testosterone values. Besides, on day 10, prolactin concentrations remained unmodified. Even though most hormonal levels were found low on day 10, all values except E2 (undetectable) corresponded to the interval reported for the diestrus phase. Likewise, histological examination of ovarian tissue from nephrotic rats showed a considerable increase in the number of atretic follicles. These findings indicate that female rats with nephrotic syndrome develop an important endocrine dysfunction that probably involves steroidogenic tissues (ovary and/or adrenal gland), and suggest the existence of a hypothalamic-hypophyseal impairment.

Animals↗
PubMed1994

Tissue lipoperoxidation and glutathione peroxidase activity in puromycin aminonucleoside injected rats.

1. Lipoperoxidation (LPx) and glutathione peroxidase (GPx) activity were measured in kidney, liver, heart, lung, brain and testis from control and puromycin aminonucleoside (PAN) injected rats on days 1-6, 8, 10, 16 and 22 after vehicle or PAN injection. 2. PAN-injected rats developed proteinuria on day 3. 3. In PAN-injected rats: (a) LPx increased in kidney, liver, lung, brain and testis before day 3 and in heart on day 3; (b) GPx activity increased in kidney, liver, heart, lung and testis and diminished in brain on day 3 or after.

Animals↗
PubMed1993

Mechanisms of ozolinone-induced renin release and diuresis.

Dextrorotatory (+) and levorotatory (-) ozolinone (ozo) were injected directly into the left renal artery of volume-expanded anesthetized dogs. (+)Ozo (40 micrograms/kg/min) had no effect on urine flow and fractional excretion of Na+, Cl-, or K+ when compared with the basal period. Comparison of (-)ozo to (+)ozo revealed the following: urine flow 4.0 +/- 0.3 v 0.9 +/- 0.1 mL/min (P < .001); FENa+ 29.8 +/- 3.0 v 5.6 +/- 0.3% (P < .001); FECl- 35.7 +/- 4.1 v 5.8 +/- 0.4% (P < .001); FEK+ 87 +/- 4 v 49 +/- 5% (P < .001). Glomerular filtration rate (GFR) and renal plasma flow (RPF) did not change. The renin secretory rate (RSR) was significantly higher with (-)ozo than with (+)ozo (498 +/- 113 v 210 +/- 53 ng A I/mL/hr.mL/min). Moreover, (-)ozo significantly increased urine PG excretion compared to basal values: 466 +/- 63 v 263 +/- 30 pg/min (P < .05). Indomethacin (2 mg/kg) markedly blunted the effects of (-)ozo on PG and RSR, and completely abolished the rise in PRA. (+)Ozo had no significant effect on urine PG excretion. Neither (-)ozo nor (+)ozo had an effect on renin production in isolated glomeruli. By contrast, (-)ozo but not (+)ozo increased PGE2 synthesis in papillary and medullary slices. The data are consistent with the proposal that the effect of (-)ozo on renin secretion and PRA is through a PG-dependent mechanism, and that it requires an intact macula densa mechanism.

Animals↗
PubMed1992

Effect of captopril on urinary excretion of renin and angiotensinogen in aminonucleoside nephrosis.

Puromycin aminonucleoside (PAN)-nephrotic rats show high plasma renin, low plasma angiotensinogen (Angt), and increased urinary excretion of renin and Angt. In this work, we studied the effect of captopril on urinary excretion of total protein, renin, and Angt for 25 days after PAN injection. Captopril had no effect on total protein urinary excretion; however, captopril did enhance the urinary excretion of renin and did decrease the urinary excretion of Angt. This seems to be due to the fact that captopril magnifies the increase in renin and the decrease in Angt in the plasma of PAN-nephrotic rats.

Angiotensinogen↗
PubMed1992

Ischemia-reperfusion induced acute renal failure in the rat is ameliorated by the spin-trapping agent alpha-phenyl-N-tert-butyl nitrone (PBN).

The spin-trapping agent alpha-phenyl-N-tert-butyl nitrone (PBN) reduced the ischemia-reperfusion induced acute renal failure in the rat. Renal ischemia was produced in unilateral nephrectomized rats by complete occlusion of the left renal artery for 60 min. Perfusion of the kidney was then reestablished, and the rats were sacrificed 48 h later. PBN (100 mg/kg i.p.) administered 30 min prior to renal artery occlusion significantly reduced the increase in serum creatinine and urea and renal failure index, as well as the decrease in urine/plasma creatinine ratio and creatinine clearance compared to saline-injected ischemic rats. PBN injected to control rats had no effect on these parameters. These data support the hypothesis of an involvement of reactive free radicals in the pathogenesis of ischemia-reperfusion induced acute renal failure in the rat and suggest that PBN may be a useful agent for the prevention of renal ischemia-reperfusion damage.

Acute Kidney Injury↗
PubMed1992

Activity of serum enzymes in puromycin aminonucleoside-induced nephrotic syndrome.

Total serum protein, serum albumin, total urine protein excretion, and the serum activity of several enzymes--aldolase (ALS), cholinesterase (CHS), leucine aminopeptidase (LAP), isocitrate dehydrogenase (ICD), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (HBD), creatine kinase (CK), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT)--were estimated in rats with nephrotic syndrome (NS) at 2, 4, 6, 8, 10, 12, 16, 20, and 30 days after a single injection of puromycin aminonucleoside (PAN). It was found that: (a) total serum protein and serum albumin diminished on day 4 and returned to control values on days 20 and 30, respectively; (b) total urine protein excretion rose on day 4, reached a peak value on day 8, and then fell substantially but still remained higher than control values on day 30; (c) ALS and CHS activities increased; (d) LAP, ICD, and AST activities showed a biphasic pattern, first increasing and then decreasing; (e) ALT, LDH, HBD, CK, and ALP activities decreased; and (f) GGT activity remained unchanged. The differences in the profiles of the enzyme activities suggest their independent regulation in experimental NS induced by PAN.

Animals↗
PubMed1991

Actinomycin D blocks the hepatic functional albumin mRNA increase in aminonucleoside-nephrotic rats.

Hepatic functional albumin-mRNA was measured in the following groups of rats: (a) puromycin aminonucleoside (PAN)-nephrotic rats, (b) PAN-nephrotic rats treated with actinomycin D prior to sacrifice, (c) control rats, and (d) control rats treated with actinomycin D. Albumin mRNA was translated in an mRNA-dependent cell-free system from rabbit reticulocyte lysate. Albumin-mRNA increased about 2-fold in PAN-nephrotic rats. This increase was abolished in vivo in PAN-nephrotic rats treated with actinomycin D. Albumin mRNA was not significantly modified in control rats treated with actinomycin D. These data suggest that the increased level of hepatic functional albumin mRNA observed in PAN-nephrotic rats in vivo was due mainly to the increased rate of albumin gene transcription.

Albumins↗
PubMed1989

Kinetic and inhibitory characteristics of serum angiotensin-converting enzyme from nine mammalian species.

1. Serum angiotensin-converting enzyme activities were obtained from nine mammalian species: rat, mouse, horse, sheep, guinea pig, hamster, rabbit, dog and man. 2. Kinetic constants (Km and Vmax) using hippuryl-L-histidyl-L-leucine as substrate and inhibitory constants (I50 and Ki) for captopril were determined for the serum ACE of each species. 3. There were important differences in the kinetic and inhibitory constants (Kms went from 6.6 mM to 1.21 mM for hamster and guinea pig; I50 ranged from 2100 nM to 3 nM for mouse and sheep) as well as differences in enzyme activity of the different species (values varied from 938 to 13 nmol hippuric acid/ml/min for guinea pig and dog serum).

Animals↗
PubMedDate not supplied

Rabbit ceruloplasmin: purification and partial characterization.

Rabbit ceruloplasmin (Cp) was purified after solid ammonium sulfate precipitation to 60% final saturation by a two-step column chromatography procedure, utilizing DEAE-Sephadex A-50 and changing the NaCl concentration in the buffer to 0.16 M to achieve the isolation of the protein. The purified Cp was used to prepare antibodies in guinea pigs that were used afterwards to determine the Cp concentration in normal rabbits and in rabbits with an experimentally induced chronic anemia. The molecular weight of rabbit Cp determined by SDS-PAGE was 125,000 and a high molecular weight Cp of 200,000 comprising 8% of the total purified protein was also found. An optical density ratio (610 nm/280 nm) of 0.0475 and a molar extinction coefficient of 7625 were obtained. Copper determinations yielded a value of 0.24% that corresponds to 5 copper atoms per molecule. The staining of Cp following discelectrophoresis in polyacrylamide gels also showed a two band pattern.

Animals↗
PubMedDate not supplied

[Intracellular messengers in the regulation of renin secretion].

The intracellular messengers that seem to be involved in renin secretion (RS) from juxtaglomerular cells (JG) are calcium (Ca), cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Unlike the majority of secretory systems, an increase in intracellular Ca concentration and calmodulin and protein kinase C activation inhibit RS. The intracellular Ca concentration in JG cells can be modified if: 1) the normal mechanisms of Ca extrusion of these cells is altered; 2) the calcium output is blocked by lanthanum; 3) the function of the voltage-sensitive Ca-channels is modified; 4) uptake or liberation of Ca from endoplasmic reticulum is modified; 5) plasmatic membrane is bypassed with calcium ionophores such as A 23187. 6) JG cells are stimulated by hormones that increase Ca and activate protein kinase C such as angiotensin II, vasopressin or alpha-1 adrenergic agonists; 7) extracellular Ca concentration increases or decreases. RS is stimulated by dibutyryl cAMP, cAMP phosphodiesterase inhibitors and by hormones and agents that activate adenylate cyclase (beta adrenergic agonists, bradykinin, histamine, forskolin and ethylcarboxamide adenosine). On the contrary, RS is inhibited by hormones and agents that inhibit adenylate cyclase such as: alpha-2 adrenergic agonists, neuropeptide Y, angiotensin II and cyclohexyladenosine. Pertussis toxin increases basal RS, blocks the inhibition by agents and hormones which inhibit adenylate cyclase and potentiate the stimulation produced by beta-adrenergic agonists. In JG cells, atrial natriuretic peptide inhibits RS, increases cGMP and decreases cAMP. The increase in cGMP correlates well with the inhibition of RS.

Calcium↗