Ethanol gastric lesion aggravated by lung injury in rat. Therapy effect ofantiulcer agents

Hemorrhagic mucosal lesions in the stomach in the rat induced by an intraga strical application of 1 ml of 50 or 75% ethanol were aggravated by precedi ng lung damage provoked by an intratracheal instillation of pyrogen-free sa line or HCl (pH 1.75) or 50-h exposure to 100% oxygen. Due to the particula r preceding aggravating circumstances, these lesions were taken to be of a special kind, rather than ordinary. So far, it is not known whether and how antiulcer agents may influence these lesions. Rats received an intratrache al (i.t.) HCl instillation [1.5 ml/kg HCl (pH 1.75)] (lung-lesion), and an intragastric instillation of 96% ethanol (gastric lesion; 1 ml/rat, 24 h af ter i.t. HCl instillation), and were sacrificed I h after ethanol. Basicall y, in lung injured rats, the subsequent ethanol-gastric lesion was markedly aggravated. This aggravation, however, in turn, did not affect the severit y of the lung lesions in the further period, at least for a 1-h observation . Taking intratracheal HCl-instillation as time 0, a gastric pentadecapepti de, GEPPPGKPADDAGLV, M.W.1419, coded BPC 157 (PL-10, PLD-116 10 mug, 10 ng, 10 pg), ranitidine (10 mg), atropine (10 mg), omeprazole (10 mg), were giv en [/kg, intraperitoneally (i.p.)] (1) once, only prophylactically [as a pr e-treatment (at -1 h), or as a co-treatment (at 0)], or only therapeuticall y (at + 18 h or + 24 h); (2) repeatedly, combining prophylactic/therapeutic regimens [(-1 h) + (+24 h) or (0) + (+24 h)], or therapeutic/therapeutic r egimens [(+18 h) + (+24 h)]. In general, the antiulcer agents did protect a gainst ethanol gastric lesions regardless of the presence of the severe lun g injury, in all of the used regimens. Of note, combining their prophylacti c and salutary regimens (at -1 h/+24 h, or at 0/+24 h) may increase the ant iulcer potential, and the effect that had been not seen already with single application, became prominent after repeated treatment. (C) 2001 Elsevier Science Ltd. All rights reserved.