Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020500 (hyperoxaluria)
 912 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interstitial calcium oxalate (CaOx) crystals can be found in primary oxalosis and in secondary hyperoxaluria. In a rat model for nephrolithiasis, we investigated whether such crystals can be removed by the surrounding interstitial cells. CaOx crystals were induced by a crystal-inducing diet based on ethylene glycol (EG) and ammonium chloride (CID). Both lithogenic compounds were added to the drinking water. After 9 days, the animals received normal drinking water for 2 days. Using this CID, only the interstitial crystals are retained. Subsequently, half of the population remained on normal drinking water (normo-oxaluria), whereas the other half received a low dose of EG alone (chronic hyperoxaluria). The rats were killed at regular times thereafter. The results showed that the kidney-associated oxalate significantly declined during normo-oxaluria, but remained high during chronic hyperoxaluria. Interstitial cells positive for the leukocyte common antigen (CD45; which identifies all types of leukocytes), the ED1 antigen (which is specific for monocytes and macrophages), and the major histocompatibility class II antigen (MCHII), respectively, had increased in number, with minor differences between both rat populations. The cells around the interstitial crystals were mostly positive for ED1. Multinucleate giant cells were regularly observed. These cells were positive for CD45 and ED1 and sometimes also for MCHII. The crystals in these cells were moderately positive for acid phosphatase and carbonic anhydrase II. It is concluded that interstitial CaOx crystals can be removed under normo-oxaluric conditions and that, in all likelihood, macrophages and multinucleate giant cells are involved in that process.
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PMID:Role of macrophages in nephrolithiasis in rats: an analysis of the renal interstitium. 1097 95

Unilateral ureteral obstruction (UUO) and hyperoxaluria (HOX) can lead to end-stage renal disease with tubulointerstitial fibrosis. We investigated the effects of enalapril (E), an ACE-inhibitor, on rat kidneys with either UUO or HOX. Sham-operated, UUO, HOX, UUO+HOX, UUO+E and HOX+E rats were killed 14 days after UUO and/or HOX was initiated. Rat kidney sections were histologically scored for tissue damage and monocyte/macrophage infiltration was demonstrated with ED1 antibody and measured by computer image analysis software. Serious glomerular and tubulointerstitial damage was found for UUO and HOX, consisting of glomerular basement membrane thickening, tubular dilatation/collapse, tubular basement membrane thickening and the infiltration of mononuclear leucocytes (mainly macrophages). For HOX, calcium oxalate crystals were visible. Neither the scored histological parameters nor monocyte/macrophage infiltration was significantly decreased when E-treated were compared with untreated groups. We conclude that E did not ameliorate the parameters scored in either UUO or HOX. This being contrary to findings by other research groups, we hypothesize that E may be effective only in short-term UUO/HOX, with transforming growth factor, TGF-beta1, formation becoming partly independent of Ang II in late-stage UUO/HOX, or other fibrogenic cytokines than TGF-beta1 becoming predominant.
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PMID:Is enalapril adequate for the prevention of renal tissue damage caused by unilateral ureteral obstruction and/or hyperoxaluria? 1271 49

Recent evidence indicates that the renin-angiotensin system (RAS) seems to play a considerable role in the development of tubulointerstitial (TI) lesions caused by hyperoxaluria (Hox). The purpose of the present study was to evaluate the specific mechanism by which Hox involving RAS induces chemokine and cytokine expression and, therefore, renal TI damage in the ethylene-glycol (ETG) induced hyperoxaluric rat model. Sprague-Dawley rats, separated into five groups, received: G1 regular water, and G2, G3, G4 and G5 1% ETG (a precursor for oxalates) in their drinking water for 4 weeks. An angiotensin converting enzyme inhibitor, benazepril (BZ) 10 mg/kg/day, angiotensin II receptor antagonists, subtype 1 (AT1) losartan (LOS) 40 mg/kg/day and subtype 2 (AT2) PD 123,319 (PD) 10 mg/kg/day, were administered daily to G3, G4 and G5, respectively. At the end of the study, the inflammatory response to Hox was evaluated using anti-NF-kappaB (p50), anti-IL-6, anti-MCP-1; anti-RANTES and anti-ED1 (monocytes/macrophages) in each group. In spite of the same urine oxalate levels, rats belonging to the hyperoxaluric groups treated with either BZ or LOS showed significantly (P<0.01) less TI lesions together with a lower immunoexpression of inflammatory mediators when compared with untreated hyperoxaluric animals. NF-kappaB (p50) was increased in tubular cells in the ETG group (43.6+/-8.7 positive cells/mm(2)) and was significantly (P<0.01) reduced by LOS (11.2+/-4 positive cells/mm(2)) and even more by BZ (6.1+/-2.4 positive cells/mm(2)). There was a significant (P<0.01) correlation between NF-kappaB (p50) positive cells and ED1 cells in the ETG group (r=0.88) and in the ETG+LOS group (r=0.92). LOS showed better control on IL-6 and MCP-1 with respect to untreated rats, while BZ showed the best control on RANTES and ED1 cells in comparison with untreated animals. Renal function was significantly (P<0.01) better preserved in BZ and LOS treated groups compared to both untreated animals and rats with PD, as indicated by creatinine clearance values. These results suggest that Hox stimulates the NF-kappaB cascade and, therefore, induces the overexpression of inflammatory mediators like IL-6, MCP-1, and RANTES. This pathway seems to be mediated not only by AT1 but also by AT2 receptors of angiotensin II.
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PMID:NF-kappaB and chemokine-cytokine expression in renal tubulointerstitium in experimental hyperoxaluria. Role of the renin-angiotensin system. 1628 84

Hyperoxaluric kidneys show an impaired diuretic response to acute infusion of L-arginine. In this study, we examined the chronic effect of l-arginine supplementation on CaOx crystal formation in hyperoxaluric rat kidneys. Eight groups were tested: control (received drinking water), L group (received L-arginine, 0.6%), LN group [received NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg)], L + LN group (received L-arginine + l-NAME), HP group [received hydroxyl-L-proline (HP, 5%) mixed with chow to induce hyperoxaluria], L + HP group (received HP + L-arginine), HP + LN group, and L + HP + LN group. The duration was 42 days, and each group had eight animals. Urinary biochemistry and renal CaOx amounts were measured, as well as renal expressions of nitric oxide synthase (NOS) isoforms and NAD(P)H oxidase. The distribution of inducible NOS (iNOS), NAD(P)H oxidase, ED1-positive cells, and nitrotyrosine was examined by immunohistochemical and immunofluorescence studies, whereas superoxide production from the kidneys was examined by fluorescence spectrometric assay. Compared with the HP group, the L + HP group had excessive CaOx crystal accumulation and enhanced endothelial NOS (eNOS), iNOS, and NAD(P)H oxidase protein expression in the kidney. Urinary excretion of nitrotyrosine was markedly increased. Increased superoxide formation in the L + HP kidney was derived from NAD(P)H oxidase and uncoupled eNOS, and increased nitrotyrosine formation might derive from iNOS and ED1-positive cells that gathered around the CaOx crystals. L-NAME cotreatment (L + HP + LN group) reduced renal oxidative nitrosative stress and tubular damage, which were induced by L + HP. The results showed that chronic l-arginine treatment to the hyperoxaluric kidney with massive CaOx crystal deposition may have a toxic effect by enhancing intrarenal oxidative and nitrosative stress.
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PMID:Chronic L-arginine administration increases oxidative and nitrosative stress in rat hyperoxaluric kidneys and excessive crystal deposition. 1844 92