Serum thioredoxin reductase levels increase in response to chemically induced acute liver injury

• Thioredoxin reductase 1 (TrxR1) levels in serum of healthy mice are low.
• Serum TrxR1 levels significantly increase upon liver injury.
• Low background of serum TrxR1 makes it sensitive to liver injury.
• Serum TrxR1 and alanine aminotransferase activities closely correlate.

BackgroundMammalian thioredoxin reductases (TrxR) are selenoproteins with important roles in antioxidant defense and redox regulation, principally linked to functions of their main substrates thioredoxins (Trx). All major forms of TrxR are intracellular while levels in serum are typically very low.MethodsSerum TrxR levels were determined with immunoblotting using antibodies against mouse TrxR1 and total enzyme activity measurements were performed, with serum and tissue samples from mouse models of liver injury, as triggered by either thioacetamide (TAA) or carbon tetrachloride (CCl4).ResultsTrxR levels in serum increased upon treatment and correlated closely with those of alanine aminotransferase (ALT), an often used serum biomarker for liver damage. In contrast, Trx1, glutathione reductase, superoxide dismutase or selenium-containing glutathione peroxidase levels in serum displayed much lower increases than TrxR or ALT.ConclusionsSerum TrxR levels are robustly elevated in mouse models of chemically induced liver injury.General significanceThe exaggerated TrxR release to serum upon liver injury may reflect more complex events than a mere passive release of hepatic enzymes to the extracellular milieu. It can also not be disregarded that enzymatically active TrxR in serum could have yet unidentified physiological functions.

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