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Application of surface-enhanced laser desorption/ionization technology to the detection and identification of urinary parvalbumin-alpha: a biomarker of compound-induced skeletal muscle toxicity in the rat.
Electrophoresis 2002; 23(18):3241-51E

Abstract

In toxicity studies, compound-induced changes are typically evaluated using a combination of endpoints and there are often a number of potential markers in biological fluids which can indicate toxic change in tissues and organs. However, some biomarkers are not specific to the organ of injury and therefore there is a continuing search for more sensitive and specific indicators of target organ toxicity. In experiments to assess the potential diagnostic usefulness of surface-enhanced laser desorption/ionization (SELDI) ProteinChip technology, skeletal muscle toxicity was induced in Wistar Han rats by administering 2,3,5,6-tetramethyl-p-phenylenediamine (TMPD). The skeletal muscle toxicity was monitored using established endpoints such as increase in serum aldolase (Aldol), aspartate aminotransferase (AST) and histopathology, and also using SELDI retentate chromatography mass spectrometry of urine samples. Clear differences in urinary protein patterns between control and TMPD-treated animals were observed on the ProteinChip surfaces. Additionally a specific urine marker protein of 11.8 kDa was identified in TMPD-dosed rats, and the detection of the marker was related to the degree of skeletal muscle toxicity assessed by recognized clinical pathology endpoints. The 11.8 kDa protein was identified as parvalbumin-alpha. These experiments demonstrated the potential of urinary parvalbumin-alpha as a specific, noninvasive, and easily detectable biomarker for skeletal muscle toxicity in the rat and the potential of SELDI technology for biomarker detection and identification in toxicology studies.

Authors+Show Affiliations

Clinical Pathology, Cellular and Biochemical Toxicology, Safety Assessment, GlaxoSmithKline Research and Development, Ware, Hertfordshire, UK. tod33742@gsk.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12298096

Citation

Dare, Theo O., et al. "Application of Surface-enhanced Laser Desorption/ionization Technology to the Detection and Identification of Urinary Parvalbumin-alpha: a Biomarker of Compound-induced Skeletal Muscle Toxicity in the Rat." Electrophoresis, vol. 23, no. 18, 2002, pp. 3241-51.
Dare TO, Davies HA, Turton JA, et al. Application of surface-enhanced laser desorption/ionization technology to the detection and identification of urinary parvalbumin-alpha: a biomarker of compound-induced skeletal muscle toxicity in the rat. Electrophoresis. 2002;23(18):3241-51.
Dare, T. O., Davies, H. A., Turton, J. A., Lomas, L., Williams, T. C., & York, M. J. (2002). Application of surface-enhanced laser desorption/ionization technology to the detection and identification of urinary parvalbumin-alpha: a biomarker of compound-induced skeletal muscle toxicity in the rat. Electrophoresis, 23(18), pp. 3241-51.
Dare TO, et al. Application of Surface-enhanced Laser Desorption/ionization Technology to the Detection and Identification of Urinary Parvalbumin-alpha: a Biomarker of Compound-induced Skeletal Muscle Toxicity in the Rat. Electrophoresis. 2002;23(18):3241-51. PubMed PMID: 12298096.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Application of surface-enhanced laser desorption/ionization technology to the detection and identification of urinary parvalbumin-alpha: a biomarker of compound-induced skeletal muscle toxicity in the rat. AU - Dare,Theo O, AU - Davies,Huw A, AU - Turton,John A, AU - Lomas,Lee, AU - Williams,Thomas C, AU - York,Malcom J, PY - 2002/9/26/pubmed PY - 2003/3/18/medline PY - 2002/9/26/entrez SP - 3241 EP - 51 JF - Electrophoresis JO - Electrophoresis VL - 23 IS - 18 N2 - In toxicity studies, compound-induced changes are typically evaluated using a combination of endpoints and there are often a number of potential markers in biological fluids which can indicate toxic change in tissues and organs. However, some biomarkers are not specific to the organ of injury and therefore there is a continuing search for more sensitive and specific indicators of target organ toxicity. In experiments to assess the potential diagnostic usefulness of surface-enhanced laser desorption/ionization (SELDI) ProteinChip technology, skeletal muscle toxicity was induced in Wistar Han rats by administering 2,3,5,6-tetramethyl-p-phenylenediamine (TMPD). The skeletal muscle toxicity was monitored using established endpoints such as increase in serum aldolase (Aldol), aspartate aminotransferase (AST) and histopathology, and also using SELDI retentate chromatography mass spectrometry of urine samples. Clear differences in urinary protein patterns between control and TMPD-treated animals were observed on the ProteinChip surfaces. Additionally a specific urine marker protein of 11.8 kDa was identified in TMPD-dosed rats, and the detection of the marker was related to the degree of skeletal muscle toxicity assessed by recognized clinical pathology endpoints. The 11.8 kDa protein was identified as parvalbumin-alpha. These experiments demonstrated the potential of urinary parvalbumin-alpha as a specific, noninvasive, and easily detectable biomarker for skeletal muscle toxicity in the rat and the potential of SELDI technology for biomarker detection and identification in toxicology studies. SN - 0173-0835 UR - https://www.unboundmedicine.com/medline/citation/12298096/Application_of_surface_enhanced_laser_desorption/ionization_technology_to_the_detection_and_identification_of_urinary_parvalbumin_alpha:_a_biomarker_of_compound_induced_skeletal_muscle_toxicity_in_the_rat_ L2 - https://doi.org/10.1002/1522-2683(200209)23:18<3241::AID-ELPS3241>3.0.CO;2-D DB - PRIME DP - Unbound Medicine ER -