Investigation on urinary proteins and renal mRNA expression in canine renal papillary necrosis induced by nefiracetam

Tsuchiya, Y.; Tominaga, Yuri; Matsubayashi, Kyuichi; Jindo, Toshimasa; Furuhama, Kazuhisa; Suzuki, Kazuo

doi:10.1007/s00204-005-0666-4

Cited by 12 publications

(5 citation statements)

References 22 publications

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“…This was the case for all healthy control dogs. The 2 faintly stained LMW bands, which appeared in electrophoresis from 3 sexually intact healthy males, were likely prostate‐specific proteins, which reportedly occur regularly in urine of healthy entire males . It has been shown, however, that the total amount of UP does not differ between healthy entire or neutered males…”

Section: Discussionmentioning

confidence: 98%

“…The 2 faintly stained LMW bands, which appeared in electrophoresis from 3 sexually intact healthy males, were likely prostate-specific proteins, which reportedly occur regularly in urine of healthy entire males. 39,40 It has been shown, however, that the total amount of UP does not differ between healthy entire or neutered males. 39 Besides the quantitative analysis of URBP/UC, the presence of tubular lesions was further emphasized in the SDS-PAGE through the high numbers of SIRS dogs with bands in the LMW ranges below 66 kDa.…”

Section: Discussionmentioning

confidence: 99%

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Quantitative and Qualitative Urine Protein Excretion in Dogs with Severe Inflammatory Response Syndrome

Schaefer

Kohn

Schweigert

et al. 2011

Veterinary Internal Medicne

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Background: Proteinuria is an established characteristic of renal disease in dogs, providing diagnostic and prognostic information. Little is known about the occurrence and severity of proteinuria in dogs with severe inflammatory response syndrome (SIRS).Hypothesis: The quantitative and qualitative urinary protein (UP) excretion is altered in dogs with SIRS. Animals: Thirty-nine dogs with SIRS and 15 healthy control dogs at admission. Methods: A case control study was performed. Diagnosis of SIRS was based on clinical and clinicopathological findings. Urinary protein (UP) was measured by a colorimetric assay. Urinary albumin (UAlb) and urinary retinol-binding protein (URBP) were measured by ELISA and quantified in relation to urinary creatinine (UC). Sodium dodecyl sulfate polyacrylamid-gel electrophoresis was conducted to identify the qualitative pattern of proteinuria. Mann-Whitney U-test was used to assess differences in UP/UC, UAlb/UC and URBP/UC between the groups. P-values < .05 were considered significant.Results: Dogs with SIRS had higher ratios of UP/UC, UAlb/UC and URBP/UC (all P < .001) in comparison to healthy control dogs. Dogs with SIRS had a total of 11 protein bands compared to 3 bands in healthy controls. In dogs with SIRS, 58% of the total counted bands were in the low molecular weight range (<60 kDa) whereas 42% were in the middle (60-80 kDa)/high molecular weight range (>80 kDa).Conclusions and Clinical Importance: SIRS alters UP excretion in dogs. Further studies should evaluate whether or not the magnitude of proteinuria is predictive of the severity and outcome of dogs with SIRS.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Quantitative and Qualitative Urine Protein Excretion in Dogs with Severe Inflammatory Response Syndrome

Schaefer

Kohn

Schweigert

et al. 2011

Veterinary Internal Medicne

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“…Clusterin is known to be up-regulated throughout the nephron in response to renal injury. For example, urinary clusterin was increased following collecting duct injury induced by lithium in rats (Dieterle et al 2010) and in niferacetam-induced RPN in dogs (Tsuchiya et al 2005). However, urinary clusterin can also be increased when proximal tubules are injured (Dieterle et al 2010; Gautier et al 2010), and clusterin has been qualified by the U.S. Food and Drug Administration (FDA) and the Europeam Medicines Agency (EMA) as a biomarker of general renal inury after review of exploratory biomarker data submissions by Critical Path Institute PSTC and HESI (Critical Path Institute 2008 and 2010; HESI 2010).…”

Section: Discussionmentioning

confidence: 99%

Biomarkers of Collecting Duct Injury in Han-Wistar and Sprague-Dawley Rats Treated with N-Phenylanthranilic Acid

et al. 2012

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N-phenylanthranilic acid is a chloride channel blocker that causes renal papillary necrosis in rats. Studies were conducted in two strains of male rats to evaluate novel biomarkers of nephrotoxicity. Han-Wistar rats were given daily oral doses of 50, 350, or up to 700 mg/kg/day of NPAA, and Sprague-Dawley rats were given 50 or 400 mg/kg/day of NPAA. Rats were euthanized on days 8 and 15. The candidate kidney injury biomarkers renal papillary antigen-1 (RPA-1, for collecting duct injury), clusterin (for general kidney injury), α-glutathione-S-transferase (a proximal tubular marker), and µ-glutathione-S-transferase (a distal tubular marker) were measured in urine by enzyme immunoassay. Characteristic degeneration and necrosis of the collecting duct and renal papilla were observed in Han-Wistar rats at the high dose on day 8 and at the mid and high doses on day 15, and in Sprague-Dawley rats given the high dose on days 8 and 15. Increases in urinary RPA-1, and to a lesser extent urine clusterin, were generally associated with the presence of collecting duct injury and were more sensitive than BUN and serum creatinine. On the other hand, decreases in α-glutathione-S-transferase without proximal tubule lesions in both strains and decreases in µ-glutathione-S-transferase in Sprague-Dawley rats only were not associated with morphological proximal or distal tubule abnormalities, so both were of less utility. It was concluded that RPA-1 is a new biomarker with utility in the detection of collecting duct injury in papillary necrosis in male rats.

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“…9C). Once in the cytoplasm, clusterin may further reduce inflammation by inhibiting NF-κB activation [50,51], thus limiting the expression of COX-2 [53,54] and proinflammatory cytokines [50]. Indeed, disruption of the clusterin gene in cells promotes NF-κB activation [50,51] and IL-6 production [50].…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, sCLU is involved in lipid transport [52] and can be induced by nefiracetam, a drug that inhibits canine renal prostaglandin synthesis and COX-2 expression through an unknown mechanism [53,54]. We therefore examined whether reduction in extracellular levels of sCLU in plaa high cells contributed to the induction of PGE 2 production.…”

Section: Overexpression Of the Plaa Gene Decreases Clusterin Expressimentioning

confidence: 99%

Alteration in the activation state of new inflammation-associated targets by phospholipase A2-activating protein (PLAA)

Zhang

Sha

Wood

et al. 2008

Cellular Signalling

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Phospholipase A 2 (PLA 2 )-activating protein (PLAA) is a novel signaling molecule that regulates the production of prostaglandins (PGE 2 ) and tumor necrosis factor (TNF)-α. To characterize the function of native PLAA in situ, we generated HeLa (Tet-off) cells overexpressing plaa (plaa high ) and control (plaa low ) cells, with the plaa gene in opposite orientation in the latter construct. The plaa high cells produced significantly more PGE 2 and interleukin (IL)-6 compared to plaa low cells in response to TNF-α. There was increased activation and/or expression of cytosolic PLA 2 , cyclooxgenase-2, and NF-κB after induction of plaa high cells with TNF-α compared to the respective plaa low cells. Microarray analysis of plaa high cells followed by functional assays revealed increased production of proinflammatory cytokine IL-32 and a decrease in the production of annexin A4 and clusterin compared to plaa low cells. We demonstrated the role of annexin A4 as an inhibitor of PLA 2 and showed that addition of exogeneous clusterin limited the production of PGE 2 from plaa high cells. To understand regulation of plaa gene expression, we used a luciferase reporter system in HeLa cells and identified one stimulatory element, with Sp1 binding sites, and one inhibitory element, in exon 1 of the plaa gene. By using decoy DNA oligonucleotides to Sp1 and competitive binding assays, we showed that Sp1 maintains basal expression of the plaa gene and binds to the above-mentioned stimulatory element. We demonstrated for the first time that the induction of native PLAA by TNF-α can perpetuate inflammation by enhancing activation of PLA 2 and NF-κB.

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Investigation on urinary proteins and renal mRNA expression in canine renal papillary necrosis induced by nefiracetam

Cited by 12 publications

References 22 publications

Quantitative and Qualitative Urine Protein Excretion in Dogs with Severe Inflammatory Response Syndrome

Quantitative and Qualitative Urine Protein Excretion in Dogs with Severe Inflammatory Response Syndrome

Biomarkers of Collecting Duct Injury in Han-Wistar and Sprague-Dawley Rats Treated with N-Phenylanthranilic Acid

Alteration in the activation state of new inflammation-associated targets by phospholipase A2-activating protein (PLAA)

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