Serum markers of mitochondrial damage and death, including glutamate dehydrogenase (GDH), nuclear DNA (nDNA) and mtDNA have been investigated as clinically useful surrogate markers capable of indicating mitochondrial lysis following hepatocyte necrosis in APAP hepatotoxicity.12,6468 There is evidence that patients who were non-survivors of APAP-induced acute liver failure had a statistically significant increase in GDH, nDNA, and mtDNA fragment levels, as compared to patients that recovered and survived their acute liver failure, inferring that more significant mitochondrial damage portends a higher mortality rate.65 The highest activity of GDH in plasma has been found in patients with markedly elevated ALT levels emanating from zone 3 of the liver, where GDH is most highly expressed and where APAP is known to case the greatest extent of liver injury.12 Moreover, the time course of the release of GDH and mtDNA has been shown to correspond well to the release of ALT from hepatocytes undergoing necrosis
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