Serum glutamate dehydrogenase activity enables early detection of liver injury in subjects with underlying muscle impairments
| Autor: | Jane Owens, Nicholas M.P. King, Roscoe L. Warner, Kent J. Johnson, David Potter, Jiri Aubrecht, Jane Larkindale, Lindsay Tomlinson, Shelli J. Schomaker, Amy C. Porter, John-Michael Sauer |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Critical Care and Emergency Medicine Pathology and Laboratory Medicine 030226 pharmacology & pharmacy Gastroenterology Biochemistry Rhabdomyolysis Dystrophin Mice 0302 clinical medicine Glutamate Dehydrogenase Medicine and Health Sciences Muscular dystrophy Hypoxia Child Creatine Kinase Trauma Medicine Liver injury Multidisciplinary Liver Diseases Healthy subjects Alanine Transaminase Animal Models Experimental Organism Systems Liver Child Preschool Biomarker (medicine) Medicine Female Anatomy Chemical and Drug Induced Liver Injury Traumatic Injury Research Article Adult medicine.medical_specialty Adolescent Science Muscle Tissue Early detection Mouse Models Gastroenterology and Hepatology Research and Analysis Methods Glutamate dehydrogenase activity 03 medical and health sciences Model Organisms Signs and Symptoms Diagnostic Medicine Internal medicine medicine Animals Humans Aspartate Aminotransferases Acetaminophen business.industry Glutamate dehydrogenase Biology and Life Sciences Proteins Cell Biology medicine.disease digestive system diseases Muscular Dystrophy Duchenne Cytoskeletal Proteins Disease Models Animal 030104 developmental biology Biological Tissue Early Diagnosis Musculoskeletal Injury Animal Studies business Biomarkers |
| Zdroj: | PLoS ONE PLoS ONE, Vol 15, Iss 5, p e0229753 (2020) |
| ISSN: | 1932-6203 |
| Popis: | Serum activities of alanine and aspartate aminotransferases (ALT and AST) are used as gold standard biomarkers for the diagnosis of hepatocellular injury. Since ALT and AST lack liver specificity, the diagnosis of the onset of hepatocellular injury in patients with underlying muscle impairments is severely limited. Thus, we evaluated the potential of glutamate dehydrogenase (GLDH) as a liver specific alternative biomarker of hepatocellular injury. In our study, serum GLDH in subjects with Duchene muscular dystrophy (DMD) was equivalent to serum GLDH in age matched healthy subjects, while serum ALT was increased 20-fold in DMD subjects. Furthermore, serum GLDH in 131 subjects with variety of muscle impairments was similar to serum GLDH of healthy subjects while serum ALT corelated with serum creatine kinase, a widely accepted biomarker of muscle impairment. In addition, significant elevations of ALT, AST, and CK were observed in a case of a patient with rhabdomyolysis, while serum GLDH stayed within the normal range until the onset of hypoxia-induced liver injury. In a mouse model of DMD (DMDmdx), serum GLDH but not serum ALT clearly correlated with the degree of acetaminophen-induced liver injury. Taken together, our data support the utility of serum GLDH as a liver-specific biomarker of liver injury that has a potential to improve diagnosis of hepatocellular injury in patients with underlying muscle impairments. In drug development, GLDH may have utility as a biomarker of drug induced liver injury in clinical trials of new therapies to treat muscle diseases such as DMD. |
| Databáze: | OpenAIRE |
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