Risk assessment of cadmium toxicity on hepatic and renal tissues of rats

Pollution and industrial practices result in concentrations of metals and other environmental agents that are related to environmental toxicity. A rat bioassay was utilized for the identification of toxic effects of cadmium intake. This demonstrated increased total urinary proteins and increased kidney weights in rats exposed to CdCl2, for 7 days, in drinking water (100 mg/L). Serum creatinine, total and direct bilirubin concentrations and alanine transaminase activity were increased in Cd-exposed rats, indicating renal and hepatic toxicity. It was also observed that lipoperoxide concentrations were increased, while Cu-Zn superoxide dismutase activity was decreased in rats treated with cadmium. This indicated that the renal and hepatic toxicity induced by cadmium involved superoxide radicals. (C) 1998 Academic Press.

Interaction of the Anti-Inflammatory Annexin A1 Protein and Tacrolimus Immunosuppressant in the Renal Function of Rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Annexin 1 mimetic peptide protects against renal ischemia/reperfusion injury in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Annexin A1 protein attenuates cyclosporine-induced renal hemodynamics changes and macrophage infiltration in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influence of tetracycline in the hepatic and renal development of rat's offspring

O objetivo deste estudo foi avaliar os possíveis efeitos da tetraciclina administrada a ratas, no décimo dia de gestação, no desenvolvimento hepático e renal de seus filhotes. O fígado mostrou vacuolização, necrose, inflamação e dilatação sinusoidal mais evidente em recém-nascidos. Mitoses, aumento precoce da população de células de Kupffer e hipertrofia de hepatócitos com maior síntese de glicogênio estavam presentes no décimo e vigésimo dias de vida. O rim mostrou vacuolização tubular e necrose discretas, mais evidentes nos recém-nascidos, assim como sinais de regeneração tubular no décimo e vigésimo dias. Esses resultados sugeriram que os órgãos estudados sofreram alterações morfológicas transitórias durante o desenvolvimento, mas apresentaram sinais de regeneração ao longo dos primeiros dias de vida.

Adrenoceptors of the medial septal area modulate water intake and renal excretory function induced by central administration of angiotensin II

We investigated the role of alpha-adrenergic antagonists and clonidine injected into the medial septal area (MSA) on water intake and the decrease in Na+, K+ and urine elicited by ANGII injection into the third ventricle (3rdV). Male Holtzman rats with stainless steel cannulas implanted into the 3rdV and MSA were used. ANGII (12 nmol/µl) increased water intake (12.5 ± 1.7 ml/120 min). Clonidine (20 nmol/µl) injected into the MSA reduced the ANGII-induced water intake (2.9 ± 0.5 ml/120 min). Pretreatment with 80 nmol/µl yohimbine or prazosin into the MSA also reduced the ANGII-induced water intake (3.0 ± 0.4 and 3.1 ± 0.2 ml/120 min, respectively). Yohimbine + prazosin + clonidine injected into the MSA abolished the ANGII-induced water intake (0.2 ± 0.1 and 0.2 ± 0.1 ml/120 min, respectively). ANGII reduced Na+ (23 ± 7 µEq/120 min), K+ (27 ± 3 µEq/120 min) and urine volume (4.3 ± 0.9 ml/120 min). Clonidine increased the parameters above. Clonidine injected into the MSA abolished the inhibitory effect of ANGII on urinary sodium. Yohimbine injected into the MSA also abolished the inhibitory effects of ANGII. Yohimbine + clonidine attenuated the inhibitory effects of ANGII. Prazosin injected into the MSA did not cause changes in ANGII responses. Prazosin + clonidine attenuated the inhibitory effects of ANGII. The results showed that MSA injections of alpha1- and alpha2-antagonists decreased ANGII-induced water intake, and abolished the Na+, K+ and urine decrease induced by ANGII into the 3rdV. These findings suggest the involvement of septal alpha1- and alpha2-adrenergic receptors in water intake and electrolyte and urine excretion induced by central ANGII.

Serotonergic mechanisms of the lateral parabrachial nucleus in renal and hormonal responses to isotonic blood volume expansion

This study investigated the involvement of serotonergic mechanisms of the lateral parabrachial nucleus (LPBN) in the control of sodium (Na+) excretion, potassium (K+) excretion, and urinary volume in unanesthetized rats subjected to acute isotonic blood volume expansion (0.15 M NaCl, 2 ml/100 g of body wt over 1 min) or control rats. Plasma oxytocin (OT), vasopressin (VP), and atrial natriuretic peptide (ANP) levels were also determined in the same protocol. Male Wistar rats with stainless steel cannulas implanted bilaterally into the LPBN were used. In rats treated with vehicle in the LPBN, blood volume expansion increased urinary volume, Na+ and K+ excretion, and also plasma ANP and OT. Bilateral injections of serotonergic receptor antagonist methysergide (1 or 4 mu g/200 eta 1) into the LPBN reduced the effects of blood volume expansion on increased Na+ and K+ excretion and urinary volume, while LPBN injections of serotonergic 5-HT2a/HT2c receptor agonist, 2.5-dimetoxi-4-iodoamphetamine hydrobromide (DOI;1 or 5 mu g/200 eta 1) enhanced the effects of blood volume expansion on Na+ and K+ excretion and urinary volume. Methysergide (4 mu g) into the LPBN decreased the effects of blood volume expansion on plasma ANP and OT, while DOI (5 mu g) increased them. The present results suggest the involvement of LPBN serotonergic mechanisms in the regulation of urinary sodium, potassium and water excretion, and hormonal responses to acute isotonic blood volume expansion.

The effects of ochratoxin/aluminosilicate interaction on the tissues and humoral immune response of broilers

This study aimed to evaluate the effect of dietary ochratoxin, in the presence or absence of aluminosilicate, on the histology of the bursa of Fabricius, liver and kidneys, and on the humoral immune response of broilers vaccinated against Newcastle disease virus. The exposure of birds to 2 p. p. m. ochratoxin, in the presence or absence of aluminosilicate, reduced their humoral immune response and the number of mitotic cells in the bursa. The relative weight of the livers of the birds exposed to this toxin was increased and, microscopically, there was hepatocyte vacuolation and megalocytosis with accompanying hyperplasia of the biliary epithelium. The kidneys showed hypertrophy of the renal proximal tubular epithelium, with thickening of the glomerular basement membrane. Aluminosilicate did not ameliorate the deleterious effects of the ochratoxin.

FTY720 in combination with cyclosporine - an analysis of skin allograft survival and renal function

Acute and chronic nephrotoxicity caused by CsA Continuous administration impair kidney allograft survival. Several clinical and experimental protocols have shown benefits to the kidney after decreasing CsA dose, withdrawing the drug or delaying its introduction after transplantation.FTY720 is a new Compound that has immunosuppressive characteristics and increase allograft survival in animal models without causing the side effects of calcineurin inhibitors (CNIs). FTY720 described mechanism of action that consists to alter the lymphocyte migration pattern without impairment of the immune system response against pathogens.In our mice model, FTY720 administered alone or in combination with CsA during 21 days increased skin allograft survival in a fully mismatched strain combination and did not cause significant changes in renal function. Moreover, renal structure was normal in all groups suggesting that at low doses (10 mg/kg/day) CsA can be associated during short-term period to other immunosuppressive drugs, i.e. FTY720 without affecting the kidney.Combination of immunosuppressive compounds with FTY720 and/or delayed introduction of low cyclosporine dose Could prevent graft rejection and avoid nephrotoxicity. (c) 2006 Elsevier B.V. All rights reserved.

EFFECTS OF DIETARY-PROTEIN, ANGIOTENSIN-I CONVERTING-ENZYME INHIBITION AND MESANGIAL OVERLOAD ON THE PROGRESSION OF ADRIAMYCIN-INDUCED NEPHROPATHY

Adriamycin, a commonly used antineoplastic antibiotic, induces glomerular lesions in rats, resulting in persistent proteinuria and glomerulosclerosis. We studied the effects of dietary protein and of an angiotensin I converting enzyme inhibitor on the progression of this nephropathy and the evolution of the histological lesions, as well as mesangial macromolecule flow. Adriamycin nephropathy was induced by injecting a single iv dose of adriamycin (3 mg/kg body weight) into the tail vein of male Wistar rats (weight, 180-200 g). In Experiment I animals with adriamycin-induced nephropathy were fed diets containing 6% (Low-Protein Diet Group = LPDG), 20% (Normal-Protein Diet Group = NPDG) and 40% (High-protein Diet Group = HPDG) protein and were observed for 30 weeks. In Experiment II the rats with adriamycin nephropathy were divided into 2 groups: ADR, that received adriamycin alone, and ADR-ENA, that received adriamycin plus enalapril, an angiotensin I converting enzyme inhibitor. The animals were sacrificed after a 24-week observation period. Six hours before sacrifice the animals were injected with I-131-ferritin and the amount of I-131-ferritin in the glomeruli was measured. In Experiment III, renal histology was performed 4, 8 and 16 weeks after adriamycin injection. At the end of Experiment I the tubulointerstitial lesion index was 2 for LPDG, 8 for NPDG, and 7.5 for HPDG (P<0.05); the frequency of glomerulosclerosis was 19 +/- 6.1% in LPDG, 42.6 +/- 6% in NPDG, and 54 +/- 9% in HPDG (P<0.05); and proteinuria was 61.1 +/- 25 mg/24 h in LPDG, 218.7 +/- 27.5 mg/24 h in NPDG, and 324.5 +/- 64.8 mg/24 h in HPDG (P<0.05). In Experiment II, at sacrifice, 24-h proteinuria was 189 +/- 16.1 mg in ADR, and 216 +/- 26.1 mg in ADR-ENA (P>0.05); the tubulointerstitial lesion index was 5 for ADR, and 5 for ADR-ENA (P>0.05); the frequency of glomerulosclerosis was 40 +/- 5.2% in ADR and 44 +/- 6% in ADR-ENA (P>0.05); the amount of I-131-ferritin in the mesangium was 214.26 +/- 22.71 cpm/mg protein in ADR and 253.77 +/- 69.72 cpm/mg protein in ADR-ENA (P>0.05). In Experiment III, sequential histological analysis revealed an acute tubulointerstitial cellular infiltrate at week 4, which was decreased at week 8. Tubular casts and dilatation were first seen at week 8 and increased at week 16 when few glomerular lesions were found. The results suggest that the tubulointerstitial lesions may play a role in the development of glomerulosclerosis in adriamycin-induced nephropathy.

ROLE OF ADRENERGIC PATHWAYS OF THE MEDIAL PREOPTIC AREA IN ANGII-INDUCED WATER-INTAKE AND RENAL EXCRETION IN RATS

In this study, we investigated the participation of adrenergic neurotransmission in angiotensin II- (ANGII)-induced water intake and urinary electrolyte excretion by means of injection of the alpha(1)-, alpha(2)-, and beta-adrenoceptor antagonists and ANGII into the medial preoptic area (MPOA) in rats. Prazosin (an alpha(1)-adrenergic antagonist) antagonized the water ingestion, Na+, K+ and urine excretion induced by ANGII, whereas yohimbine (an alpha(2)-adrenergic antagonist) enhanced the Na+, K+ and urine excretion induced by ANGII. Propranolol (a nonselective beta-adrenoceptor blocker) antagonized the water ingestion and enhanced the Na+ and urine excretion induced by ANGII. Previous treatment with prazosin reduced the presser responses to ANGII, whereas yohimbine had opposite effects. Previous injection of propranolol produced no effects in the presser responses to ANGII. These results suggest that the adrenergic neurotransmission in the MPOA may actively participate in ANGII-induced dipsogenesis, natriuresis, kaliuresis and diuresis in a process that involves alpha(1)-, alpha(2)-, and beta-adrenoceptors.

Effect of renoguanylin on hydrogen/bicarbonate ion transport in rat renal tubules

Renoguanylin (REN) is a recently described member of the guanylin family, which was first isolated from eels and is expressed in intestinal and specially kidney tissues. In the present work we evaluate the effects of REN on the mechanisms of hydrogen transport in rat renal tubules by the stationary microperfusion method. We evaluated the effect of 1 mu M and 10 mu M of renoguanylin (REN) on the reabsorption of bicarbonate in proximal and distal segments and found that there was a significant reduction in bicarbonate reabsorption. In proximal segments, REN promoted a significant effect at both 1 and 10 mu M concentrations. Comparing control and REN concentration of 1 mu M, JHCO(3)(-) . nmol cm(-2) s(-1) -1,76 +/- 0.11(control) x 1,29 +/- 0,08(REN) 10 mu m: P<0.05, was obtained. In distal segments the effect of both concentrations of REN was also effective, being significant e.g. at a concentration of 1 mu M (JHCO(3)(-), nmol cm(-2) s(-1) -0.80 +/- 0.07(control) x 0.60 +/- 0.06(REN) 1 mu m; P<0.05), although at a lower level than in the proximal tubule. Our results suggest that the action of REN on hydrogen transport involves the inhibition of Na(+)/H(+) exchanger and H(+)-ATPase in the luminal membrane of the perfused tubules by a PKG dependent pathway. (c) 2009 Elsevier B.V. All rights reserved.

Cryoablation vs radiofrequency ablation for the treatment of renal cell carcinoma: a meta-analysis of case series studies

OBJECTIVETo determine the current status of the literature regarding the clinical efficacy and complication rates of cryoablation vs radiofrequency ablation in the treatment of small renal tumours.METHODSA review of the literature was conducted. There was no language restriction. Studies were obtained from the following sources: MEDLINE, EMBASE and LILACS.Inclusion criteria were (i) case series design with more than one case reported, (ii) use of cryoablation or radiofrequency ablation, (iii) patients with renal cell carcinoma and, (iv) outcome reported as clinical efficacy.When available, we also quantified the complication rates from each included study.Proportional meta-analysis was performed on both outcomes with a random-effects model. The 95% confidential intervals were also calculated.RESULTSThirty-one case series (20 cryoablation, 11 radiofrequency ablation) met all inclusion criteria.The pooled proportion of clinical efficacy was 89% in cryoablation therapy from a total of 457 cases. There was a statistically significant heterogeneity between these studies showing the inconsistency of clinical and methodological aspects.The pooled proportion of clinical efficacy was 90% in radiofrequency ablation therapy from a total of 426 cases. There was no statistically significant heterogeneity between these studies.There was no statistically significant difference regarding complications rate between cryoablation and radiofrequency ablation.CONCLUSIONSThis review shows that both ablation therapies have similar efficacy and complication rates.There is urgency for performing clinical trials with long-term data to establish which intervention is most suitable for the treatment of small renal masses.

Pleiotropic effects of statins may improve outcomes in atherosclerotic renovascular disease

BACKGROUNDAtherosclerotic renovascular disease (ARD) coexists with arterial obstructive disease in the coronary, cerebral, and peripheral arteries that may remain underdiagnosed and untreated.METHODSThis retrospective study compares overall survival and renal survival (i.e., time to doubling of serum creatinine or end-stage renal disease (ESRD)) over an 11-year period in 104 ARD patients of whom 68 received statin therapy (group S) because of elevated lipid levels and 36 had no statin (group NS) because of normal lipid profile at entry.RESULTSAtherosclerosis in another vascular bed was documented in 84%. Lipid profiles at end point were virtually identical in both the groups Group S had mean survival 123 months (confidence interval (CI) 113-134) with four deaths, and mean renal survival 122 months (CI 113-131). Group NS had mean survival 33 months (CI 23-42) with 13 deaths, and mean renal survival 27 months (CI 17-37).CONCLUSIONSStatin therapy was associated with lesser rate of progression of renal insufficiency (with 7.4% of S patients reaching renal end points vs. 38.9% of NS patients) and lower overall mortality (5.9% in S vs. 36.1% in NS patients), P < 0.001 for both. Although both groups received what was deemed optimal therapy, they did have other differences that may have affected the outcomes (a limitation addressed by Cox multiple regression analysis). These results suggest the need for prospective randomized controlled studies in ARD patients in order to explore potential benefits of statins that may not be attributable solely to lipid lowering.

A2 Noradrenergic Lesions Prevent Renal Sympathoinhibition Induced by Hypernatremia in Rats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)