Proteomics ofS-(1, 2-dichlorovinyl)-<scp>l</scp>-cysteine-induced acute renal failure and autoprotection in mice

Korrapati, Midhun C.; Chilakapati, Jaya; Witzmann, Frank A.; Rao, C S; Lock, Edward A.; Mehendale, Harihara M.

doi:10.1152/ajprenal.00114.2007

Cited by 18 publications

(7 citation statements)

References 70 publications

(80 reference statements)

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“…were equivalent, and slightly higher at 10 mg/kg i.p. Compared with the acute exposure experiments (Korrapati et al, 2005(Korrapati et al, , 2006(Korrapati et al, and 2007Terracini and Parker, 1965), pathohistological symptoms such as dilatation of renal tubule, tubular necrosis and interstitial fibrosis observed at DCVC 30 mg/kg p.o. and i.p were not markedly different.…”

Section: Discussionmentioning

confidence: 74%

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Nephrotoxic effect of subchronic exposure to S-(1,2-dichlorovinyl)-L-cysteine in mice

et al. 2012

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-The effect of subchronic exposure of S-(1,2-dichlorovinyl)-L-cysteine (DCVC), an active metabolite of trichloroethylene (TCE), was investigated in mice, as a part of mechanistic assessment of renal toxicity of TCE. To examine the subchronic effects of DCVC on kidney function, Balb/c male mice were administered DCVC orally and intraperitoneally once a week for 13 weeks at 1, 10 and 30 mg/kg (Main Study) and for 8 weeks at 30 mg/kg (PCR Study). At the terminal sacrifice, mice orally and intraperitoneally administered with 10 and 30 mg/kg showed significantly lower kidney weight and significantly higher blood urea nitrogen levels than the control group. Pathological examination revealed that a dose of 30 mg/kg delivered by both routes resulted in renal tubular degeneration characterized by tubular necrosis and interstitial fibrosis, and in degradation of the cortex. Degenerative changes were accompanied by the increased expression of tumor necrosis factor-α, interleukin-6 and cyclooxygenase-2 mRNAs in the kidney of mice treated with 30 mg/kg for 8 weeks. These pathohistological observations mostly corresponded to those in short-term toxicity studies on DCVC. DCVC might be a direct cause of renal toxicity, which is suggested from the aggravation in these symptoms with the dose increase.

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Section: Discussionmentioning

confidence: 74%

“…At high doses (75 mg/kg), DCVC causes acute, lethal renal failure which is characterized morphologically by intensely eosinophilic and necrotic proximal tubular epithelium with some exfoliation of cellular detritus into tubular lumens (Korrapati et al, 2005(Korrapati et al, , 2006(Korrapati et al, and 2007.…”

Section: Introductionmentioning

confidence: 99%

Nephrotoxic effect of subchronic exposure to S-(1,2-dichlorovinyl)-L-cysteine in mice

et al. 2012

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“…Many more studies used cell lines derived from various nephron regions with the major limitation that it remains unclear how far these cell lines reflect the in-vivo situation 88 . Most studies have applied proteomics to study disease processes using whole kidney tissue as material 55,[89][90][91][92][93][94] . Obviously, this approach is simple and fast but has major limitations due to the morphological diversity and complexity of the kidney.…”

Section: Application Of Proteomics To Normal and Diseased Kidney Funcmentioning

confidence: 99%

Toward Quantitative Proteomics of Organ Substructures: Implications for Renal Physiology

Velić

Maček

Wagner

2010

Seminars in Nephrology

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AcknowledgementsResearch in the laboratories of the authors has been supported by grants from the Minstry of Science, Baden-Wuerttenberg (to BM) and the Swiss National Science Foundation, the 6 th and 7 th EU Framework projects (EuReGene and EUNEFRON) (to CAW). We thank MatthiasMann for critically reading and discussing the manuscript. Summary 2Organs are complex structures that consist of multiple tissues with different levels of gene expression. To achieve a comprehensive coverage and accurate quantitation data, organs should ideally be separated into morphological and/or functional substructures prior to gene or protein expression analysis. However, due to complex morphology and elaborate isolation protocols, this was so far often difficult to achieve. Kidneys are organs where functional and morphological subdivision is especially important. Each subunit of the kidney, the nephron, itself consists of more than 10 subsegments with distinct morphological and functional characteristics. For a full understanding of kidney physiology, global gene and protein expression analyses have to be performed at the level of the nephron subsegments; however, such studies have so far been extremely rare.Here we describe the latest approaches in quantitative high accuracy mass spectrometrybased proteomics and their application to quantitative proteomics studies of the whole kidney and nephron subsegments, both in humans and in animal models. We compare these studies with similar studies performed on other organ substructures. We argue that the newest technologies used for preparation, processing and measurement of small amounts of starting material are finally enabling global and subsegment-specific quantitative measurement of protein levels in the kidney and other organs. These new technologies and approaches are making a decisive impact on our understanding of the (patho)physiological processes at the molecular level.3

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“…Korrapati et al [120] identified proteins indicative of DCVC-induced acute renal failure and autoprotection in mice using conventional, large-format 2-DE, Coomassie brilliant blue-based visualization, and MS/MS. Low-dose exposure (15 mg DCVC/kg i.p.)…”

Section: Toxicoproteomic Studies In Kidney Injurymentioning

confidence: 99%

The role of toxicoproteomics in assessing organ specific toxicity

Merrick

Witzmann

2009

Experientia Supplementum

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Aims of this chapter on the role of toxicoproteomics in assessing organ-specific toxicity are to define the field of toxicoproteomics, describe its development among global technologies, and show potential uses in experimental toxicological research, preclinical testing and mechanistic biological research. Disciplines within proteomics deployed in preclinical research are described as Tier I analysis, involving global protein mapping and protein profiling for differential expression, and Tier II proteomic analysis, including global methods for description of function, structure, interactions and post-translational modification of proteins. Proteomic platforms used in toxicoproteomics research are briefly reviewed. Preclinical toxicoproteomic studies with model liver and kidney toxicants are critically assessed for their contributions toward understanding pathophysiology and in biomarker discovery. Toxicoproteomics research conducted in other organs and tissues are briefly discussed as well. The final section suggests several key developments involving new approaches and research focus areas for the field of toxicoproteomics as a new tool for toxicological pathology.

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Proteomics ofS-(1, 2-dichlorovinyl)-l-cysteine-induced acute renal failure and autoprotection in mice

Cited by 18 publications

References 70 publications

Nephrotoxic effect of subchronic exposure to <i>S</i>-(1,2-dichlorovinyl)-<i>L</i>-cysteine in mice

Nephrotoxic effect of subchronic exposure to <i>S</i>-(1,2-dichlorovinyl)-<i>L</i>-cysteine in mice

Toward Quantitative Proteomics of Organ Substructures: Implications for Renal Physiology

The role of toxicoproteomics in assessing organ specific toxicity

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