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Reversal of ethanol and indomethacin‐induced suppression of hepatic DNA synthesis by 16,16‐dimethyl prostaglandin E2

Investigations were undertaken to determine effectiveness of 16,16‐dimethyl prostaglandin E2 (dmPGE2) in overcoming the suppressive effects of ethanol and/or indomethacin on hepatic DNA synthesis. Adult litter mate Sprague‐Dawley rats were subjected to sham operation or partial hepatectomy. Immediately after partial hepatectomy, and at 8‐hr intervals for 24 hr, the rats were given: (a) ethanol with and without dmPGE2 or (b) indomethacin with and without ethanol and/or dmPGE2. DmPGE2 produced a significant increase in DNA synthesis in sham‐operated (p < 0.001) and untreated partially hepatectomized animals (p < 0.025). Ethanol and indomethacin caused a 6‐ and 18‐fold reduction, respectively, in hepatic DNA synthesis following partial hepatectomy. DmPGE2 overcame the inhibitory effect of ethanol (p < 0.005) and indomethacin (p < 0.0005) in partially hepatectomized animals. Mitoses were decreased concomitantly with ethanol and/or indomethacin‐induced reduction in DNA synthesis and increased with administration of dmPGE2.