Antioxidant Functionality in Hepatocytes Using the Enhanced Collagen Extracellular Matrix Under Different Oxygen Tensions

Abstract

Improvement of O₂ supply in bioartificial liver devices remains a critical issue in maintaining hepatocyte viability and functions. Therefore, the current study investigates whether enhanced oxygen (O₂) transport through collagen extracellular matrix (ECM) can produce a more stable antioxidant defense in different O₂ tensions during prolonged incubation times. Total glutathione concentration of cultured hepatocytes in enhanced ECM was significantly higher than in normal ECM under the lowest O₂ tension phase (2.60mm of thickness from O₂ source), and was also significantly increased in 0.52mm transport distance of hypoxia as compared to normoxic conditions. Catalase and glutathione reductase activities for hepatocytes within enhanced ECM were also significantly preserved relative to their values for the normal collagen ECM. Specifically, the enhanced ECM produced higher activities at a further transport distance (1.56mm) from the O₂ source at the 24 h time-point, and remained higher up to the 96 h incubation time. In contrast, the glutathione peroxidase activities in both collagen ECM systems were similar. Hepatocyte viability in the enhanced ECM system was also consistently greater than that for normal ECM. These results suggest that the O₂ enhanced collagen ECM preserves the antioxidant defense system as compared to normal collagen ECM, ostensibly via increased micropathways for O₂ transport to the hepatocytes.