Downard C D, Roberts L J, Morrow J D
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
Clin Pharmacol Ther. 1995 Apr;57(4):441-5. doi: 10.1016/0009-9236(95)90214-7.
Benzoic acid is one of the most commonly used preservatives in cosmetics, foodstuffs, and drug preparations. Nonetheless, products containing this compound frequently induce cutaneous erythema. Previous studies have suggested that prostaglandins may mediate the cutaneous vasodilation because ingestion of cyclooxygenase inhibitors before the application of benzoic acid markedly diminishes this symptom. However, the prostaglandin responsible has not been conclusively determined. Recently we showed that cutaneous erythema similar to that associated with application of venzoic acid is induced by the topical administration of another preservative, sorbic acid, and is mediated by the increased biosynthesis of prostaglandin (PG)D2 in the skin. This study was designed to determine whether the cutaneous vasodilation induced by benzoic acid is mediated by this prostaglandin in humans.
Benzoic acid (10% in petrolatum) was applied to the forearms of healthy volunteers. Blood was obtained from the antecubital vein draining the treated site and assayed for vasodilating prostaglandins and histamine.
Topical application of benzoic acid to four volunteers resulted in a 29- to 8000-fold increase in plasma levels of PGD2 and a 72- to 370-fold increase in levels of 9 alpha,11 beta-PGF2, the stable plasma metabolite of PGD2, in blood drawn from the antecubital vein draining the treated sites. In contrast, there were no changes in plasma levels of other vasodilating prostaglandins, PGE2 or prostacyclin (PGI2). Increases in levels of PGD2 and 9 alpha,11 beta-PGF2 were not found in blood drawn simultaneously from veins in the contralateral arm, indicating the increased biosynthesis of PGD2 from the site of benzoic acid application. Increased formation of PGD2 in response to topical application of benzoic acid was dose dependent over a concentration range of 0.01% to 15%. The increased synthesis of PGD2 was not accompanied by a release of histamine, suggesting that PGD2 was not derived from the mast cell.
PGD2 mediates the vasodilation associated with topical application of benzoic acid.
苯甲酸是化妆品、食品和药物制剂中最常用的防腐剂之一。尽管如此，含有这种化合物的产品经常会引起皮肤红斑。先前的研究表明，前列腺素可能介导皮肤血管舒张，因为在应用苯甲酸之前摄入环氧合酶抑制剂可显著减轻这种症状。然而，尚未最终确定起作用的前列腺素。最近我们发现，局部应用另一种防腐剂山梨酸会诱发与应用苯甲酸相关的类似皮肤红斑，且由皮肤中前列腺素（PG）D2生物合成增加所介导。本研究旨在确定苯甲酸诱发的皮肤血管舒张在人体中是否由这种前列腺素介导。
将苯甲酸（凡士林基质中含10%）涂抹于健康志愿者的前臂。从前臂接受治疗部位引流的肘前静脉采集血液，检测血管舒张性前列腺素和组胺。
对4名志愿者局部应用苯甲酸后，从前臂接受治疗部位引流的肘前静脉采集的血液中，血浆PGD2水平增加了29至8000倍，PGD2的稳定血浆代谢物9α,11β - PGF2水平增加了72至370倍。相比之下，其他血管舒张性前列腺素PGE2或前列环素（PGI2）的血浆水平没有变化。从对侧手臂静脉同时采集的血液中未发现PGD2和9α,11β - PGF2水平升高，表明苯甲酸应用部位PGD2生物合成增加。在0.01%至15%的浓度范围内，局部应用苯甲酸后PGD2的生成增加呈剂量依赖性。PGD2合成增加并未伴随组胺释放，提示PGD2并非来源于肥大细胞。
PGD介导了与局部应用苯甲酸相关的血管舒张。
