Blandizzi C, Gherardi G, Marveggio C, Lazzeri G, Natale G, Carignani D, Colucci R, Del Tacca M
Institute of Pharmacology, School of Medicine and Dentistry, University of Pisa, Italy.
Dig Dis Sci. 1997 Jun;42(6):1233-41. doi: 10.1023/a:1018806224461.
Suramin is currently used in clinical practice as antineoplastic agent because of its complex interaction with the biological activity of various growth factors involved in tumor progression. The influence exerted by suramin on gastric injury induced in rats by intraluminal injection of absolute ethanol was investigated in the present study. The morphometric analysis of gastric histological sections revealed that suramin, 18 mg/kg, administered intraperitoneally for 14 days every other day, caused a marked enhancement of ethanol-induced mucosal damage. This effect was more pronounced 1-8 hr following ethanol administration, and it was still significant after 48 hr. In suramin-treated animals the evaluation of Alcian blue recovery from gastric-bound mucus showed that the levels of adherent mucus were significantly lower than those detected in untreated rats. In addition, pretreatment with suramin did not modify basal acid secretion, but caused potentiation of acid output stimulated by pylorus ligation or electrical vagal stimulation. Overall, the present results indicate that suramin exerts a negative influence on both gastric protective and repairing mechanisms. Due to the peculiar pharmacodynamic profile of suramin, it is suggested that interference with endogenous growth factors, endowed with physiological protective activity on gastric mucosa, might account for the damage-enhancing action of this drug.
由于苏拉明与肿瘤进展中涉及的各种生长因子的生物活性存在复杂相互作用,目前它在临床实践中被用作抗肿瘤药物。本研究调查了苏拉明对大鼠经腔内注射无水乙醇诱导的胃损伤的影响。胃组织学切片的形态计量分析显示,每隔一天腹腔注射18mg/kg的苏拉明,持续14天,会导致乙醇诱导的黏膜损伤显著加重。这种效应在乙醇给药后1 - 8小时更为明显,48小时后仍很显著。在接受苏拉明治疗的动物中,对胃结合黏液中阿尔新蓝回收率的评估表明,黏附黏液的水平显著低于未治疗大鼠。此外,苏拉明预处理并未改变基础胃酸分泌,但会增强幽门结扎或电迷走神经刺激所诱发的胃酸分泌。总体而言,目前的结果表明苏拉明对胃保护和修复机制均产生负面影响。鉴于苏拉明独特的药效学特征,提示对胃黏膜具有生理保护活性的内源性生长因子的干扰可能是该药物损伤增强作用的原因。