Tetraprenylacetone promotes healing process of ethanol-induced gastric damage in the rat

Tetraprenylacetone (TPA: teprenon, geranylgeranylacetone) is a novel anti-ulcer agent developed in Japan. The aim of this study was to test whether TPA has the ability to promote the healing process of rat gastric mucosal injury induced by absolute ethanol (ET). Fasted rats received orally 5 ml/kg of absolute ET. Sixty minutes later, TPA (200 mg/kg) or saline (control) was administered intragastrically. Thereafter, the same dose of TPA or saline was given orally every 8 hours. To investigate the role of endogenous prostaglandins, indomethacin was given intraperitoneally every 8 hours. Twenty four or 48 hours after the first administration of TPA or saline, rats were sacrificed and the stomachs were removed. Administration of TPA significantly reduced lesion indices from 100 +/- 12.9% (control) to 57.0 +/- 12.8% (24 hours, P less than 0.05) and from 100 +/- 15.3% (control) to 17.6 +/- 3.4% (48 hours, P less than 0.01). Addition of indomethacin did not significantly affect this effect of TPA. Ultrastructural studies revealed that TPA stimulated regeneration of gastric mucosa damaged by ET after 24 and 48 hours. These results indicate that TPA has the ability to promote the healing process of gastric mucosal damage induced by absolute ET. It is, however, unlikely that endogenous prostaglandins are involved in this promotive effect of TPA on the healing process of gastric injury.