Prevention of Respiratory Decline in Necrotic Liver Degeneration by Antioxidants in vitro

Summary The effect of 13 antioxidants on liver slices during the latent phase of necrotic liver degeneration, was studied in vitro. The characteristic respiratory decline, i.e., breakdown of O2 consumption in the Warburg apparatus, was prevented by addition of most compounds at catalytic dose levels. With increasing amounts of compounds, dose response curves were obtained. The scale of relative potencies in vitro followed closely that previously established in vivo for protection against liver necrosis by feeding of the compounds, as well as for reversal of respiratory decline by intraportal injection, with the exception of Vit. E and methylene blue. Tocopherol and its esters were completely inactive in vitro, while the tocopherol metabolite showed high potency in preventing the metabolic lesion. Methylene blue, inactive in the in vivo systems, was highly potent in the Warburg assay. The most potent substance DPPD, produced a significant effect with .06 μg/100 mg of liver tissue in 3 cc medium. Santoquin, Santoflex B and amylhydroquinone were effective at doses from less than 1 to 6 μg. Less protection was found with phenolic compounds, such as NDGA, Propylgallate, DBPC and BHA; hydroquinone and Propylparasept were without activity. It is concluded that the substances act directly in the liver cell, perhaps not merely as antioxidants but as catalysts in intermediary metabolism.