Cytoprotective effect of prostaglandins on isolated rat liver cells

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Abstract
In vitro studies were carried out on isolated rat hepatocytes to examine the cytoprotective actions of prostaglandins (PG), using CCl4 as the toxic agent. Isolated hepatocytes, prepared by collagenase, were cultured in Leibowitz-15 medium. Following preincubation, CCl4(300 or 150 .mu.g/ml) was added to the hepatocytes. Treatment with Indomethacin (INDO), 16, 16-dimethyl-PGE2(PGE2) and prostacyclin (PGI2) was assayed in the cultures. Cell damage was measured by lactic dehydrogenase (LDH) release. 6-keto-PGF1.alpha. was measured in the supernatant by direct radioimmunoassay. PGI2(30.0 ng/ml) treatment 30 min after CCl4(300 .mu.g/ml) addition was highly protective (P < 0.001 vs. CCl4 control). PGE2(3 ng/ml) showed similar protection (P < 0.001). INDO (2 .mu.g/ml) following CCl4(150 .mu.g/ml) demonstrated increased cell death (P < 0.001). INDO (0.5 .mu.g/ml) reduced 6-keto-PGF1.alpha. production (P < 0.05). Low dose ethanol (1.5 .mu.g/ml) increased 6-keto-PGF1.alpha. production (P < 0.05). Ethanol (1.5 .mu.g/ml), added to stimulate endogenous PG production, was cytoprotective when added prior to CCl4 (P < 0.01). This protection was suppressed by INDO. Ethanol added after CCl4 was not protective. Exogenously added PGI2 and PGE2 are cytoprotective in this in vitro model, and endogenous PG production may play a protective role in the initial stages of cellular damage.