Selected Studies on the Protective Effect of Prostaglandins against CCL4-Induced Hepatic Necrosis
Mochizuki, Ronald M.
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16,16 dimethyl PGE2 has been found to protect the liver of rats from the effects of a variety of necrotizing agents such as carbon tetrachloride. To determine whether this protection reflected a delay in necrosis, a time course study was undertaken with rats receiving CC1 4 with and without 16,16 dimethyl PGE2 treatment. In this study 16,16 dimethyl PGE2 was not found to alter the time course of CCl 4-induced necrosis, but did produce significantly improve levels of biochemical serum parameters of liver function at 24 and 48 hrs. At 72 and 96 hrs both vehicle and PG-treated groups had essentially normal liver function parameters. The naturally occurring prostaglandin, PGE2, did not provide significant protection to the liver from an acute dose of CCl 4 as monitored by the biochemical serum parameters. However, the analog 15 R 15 methyl PGE2 significantly improved bilirubin and alkaline phosphatase levels, which indicates a degree of hepatic protection from CCl 4. When 16,16 dimethyl PGE2 was given concurrently with long-term (chronic) CC1 4 administration, bilirubin levels were significantly improved, and other parameters showed trends toward hepatic protection. 16,16 dimethyl PGE2 did not appear to have an effect on the healing process of livers made necrotic by chronic CC1 4 administration when given 2x daily for a 2 week period after discontinued CCl 4 treatment.