Use of Proteomic Methods to Identify Serum Biomarkers Associated with Rat Liver Toxicity or Hypertrophy

Amacher, David E.; Adler, Rick R.; Herath, Athula; Townsend, R. Reid

doi:10.1373/clinchem.2005.049908

Cited by 89 publications

(57 citation statements)

References 44 publications

(15 reference statements)

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“…Changes in protein expression were determined as a ratio of the mean Clinical Chemistry 53, No. 10,2007 percentages of feature volumes. Only features present in at least 66% of individual gels belonging to either the control or hepatic-scarring groups were considered for differential analysis (i.e., present in at least 2 of the 3 moderate fibrosis gels and 3 of the 4 control, mild fibrosis, and cirrhosis gels).…”

Section: Differential Image Analysismentioning

confidence: 99%

Novel Serum Biomarker Candidates for Liver Fibrosis in Hepatitis C Patients

Gangadharan¹,

et al. 2007

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Background: Liver biopsy is currently the gold standard for assessing liver fibrosis, and no reliable noninvasive diagnostic approach is available. Therefore a suitable serologic biomarker of liver fibrosis is urgently needed. Methods: We used a proteomics method based on 2-dimensional gel electrophoresis to identify potential fibrosis biomarkers. Serum samples from patients with varying degrees of hepatic scarring induced by infection with the hepatitis C virus (HCV) were analyzed and compared with serum from healthy controls. Results: We observed the most prominent differences when we compared serum samples from cirrhotic patients with healthy control serum. Inter-␣-trypsin inhibitor heavy chain H4 (ITIH4) fragments, ␣1 antichymotrypsin, apolipoprotein L1 (Apo L1), prealbumin, albumin, paraoxonase/arylesterase 1, and zinc-␣2-glycoprotein were decreased in cirrhotic serum, whereas CD5 antigen-like protein (CD5L) and ␤2 glycoprotein I (␤2GPI) were increased. In general, ␣2 macroglobulin (a2M) and immunoglobulin components increased with hepatic fibrosis, whereas haptoglobin and complement components (C3, C4, and factor H-related protein 1) decreased. Novel proteins associated with HCV-induced fibrosis included ITIH4 fragments, complement factor H-related protein 1, CD5L, Apo L1, ␤2GPI, and thioester-cleaved products of a2M. Conclusions: Assessment of hepatic scarring may be performed with a combination of these novel fibrosis biomarkers, thus eliminating the need for liver biopsy. Further evaluation of these candidate markers needs to be performed in larger patient populations. Diagnosis

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Section: Differential Image Analysismentioning

confidence: 99%

Novel Serum Biomarker Candidates for Liver Fibrosis in Hepatitis C Patients

Gangadharan¹,

et al. 2007

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“…An ideal marker of xenobioticinduced hepatic toxicity must have a substantial tissue to plasma ratio; is of liver origin (exclusively or predominantly), or its level is affected by a change in liver function (tissue specific); can be reliably measured at sublethal doses of a xenobiotic (highly sensitive); should persist in plasma for several hours to provide a convenient diagnostic time window but not so long that recurrent injury would not be identified (reliability); and it must be easily confirmed to be associated with histopathological or functional changes in the liver (relevancy) [7]. The factors that determine these characteristics and the sensitivity and specificity of each marker are size, cellular localization, solubility, release ratio, clearance, specificity for irreversible injury, and detectability [8].…”

Section: Introductionmentioning

confidence: 99%

Biochemical Markers of In Vivo Hepatotoxicity

Wm¹,

DW²

2016

J Clin Toxicol

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A chemical compound, whether of natural or of synthetic origin, brings about a toxicological effect when its dose is high enough or the duration of exposure is sufficient to cause an alteration in the normal homeostasis of body fluids and tissues. Therefore, the right dose differentiates a toxicant from a remedy. The body detoxifies drugs and other chemical compounds through key organs such as the liver. The liver plays a central role in the metabolism and excretion of xenobiotics which makes it highly susceptible to their adverse and toxic effects. These effects can be manifested in the form of hepatic injuries, which take many forms from cellular degeneration and necrosis to cirrhosis or cholestasis to vascular injury. Exposure to hepatotoxicants alters the homeostatic balance of various biological markers that provides a powerful and dynamic approach to understanding the spectrum of liver diseases. These markers offer a means for homogeneous classification of a disease and risk factor, and they can extend one's basic information about the underlying pathogenesis of disease and in drug design.

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“…Many studies have been conducted to identify more reliable and sensitive early blood markers for liver injury by using various high throughput technologies such as protein mass spectrometry and gene expression arrays (3,4). These efforts have so far yielded candidates that perform no better than the existing aminotransferase-based markers.…”

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confidence: 99%

Circulating microRNAs, potential biomarkers for drug-induced liver injury

Wang

Zhang²,

Marzolf³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

1,070

957

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Drug-induced liver injury is a frequent side effect of many drugs, constitutes a significant threat to patient health and has an enormous economic impact on health care expenditures. Numerous efforts have been made to identify reliable and predictive markers to detect the early signs of drug-induced injury to the liver, one of the most vulnerable organs in the body. These studies have, however, not delivered any more informative candidates than the serum aminotransferase markers that have been available for Ϸ30 years. Using acetaminophen overdose-induced liver injury in the mouse as a model system, we have observed highly significant differences in the spectrum and levels of microRNAs in both liver tissues and in plasma between control and overdosed animals. Based on our survey of microRNA expression among normal tissues, some of the microRNAs, like messenger RNAs, display restricted tissue distributions. A number of elevated circulating microRNAs in plasma collected from acetaminophen-overdosed animals are highly expressed in the liver. We have demonstrated that specific microRNA species, such as mir-122 and mir-192, both are enriched in the liver tissue and exhibit dose-and exposure duration-dependent changes in the plasma that parallel serum aminotransferase levels and the histopathology of liver degeneration, but their changes can be detected significantly earlier. These findings suggest the potential of using specific circulating microRNAs as sensitive and informative biomarkers for drug-induced liver injury.acetaminophen overdose ͉ plasma ͉ miRNA ͉ toxicity ͉ ALT

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Use of Proteomic Methods to Identify Serum Biomarkers Associated with Rat Liver Toxicity or Hypertrophy

Cited by 89 publications

References 44 publications

Novel Serum Biomarker Candidates for Liver Fibrosis in Hepatitis C Patients

Novel Serum Biomarker Candidates for Liver Fibrosis in Hepatitis C Patients

Biochemical Markers of In Vivo Hepatotoxicity

Circulating microRNAs, potential biomarkers for drug-induced liver injury

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