Barreto J C, Smith G S, Tornwall M S, Miller T A
Department of Surgery, University of Texas Medical School, Houston 77030.
Am J Physiol. 1993 Mar;264(3 Pt 1):G422-6. doi: 10.1152/ajpgi.1993.264.3.G422.
N-acetylcysteine (NAC), when administered orally as a 20% solution, is a potent protective agent against gastric injury in the rat stomach induced by absolute ethanol. The present study was undertaken to define the means by which this protection is mediated. The notion that NAC acts as a glutathione precursor was excluded when N-acetylserine (NAS) was noted to be equally protective against alcohol injury. The NAS molecule contains a hydroxyl moiety at the site where NAC contains a sulfhydryl. To orally administer 20% NAC at a neutral pH, NaOH is added to the free acid form to keep NAC in solution. We determined by titration that a sodium concentration of 1.2 M results. Thus it became apparent that the protective effect of NAC might be mediated through the sodium employed to titrate NAC. Accordingly, we examined various sodium salts and assessed their relative protective effects against alcohol injury. Both sodium acetate and sodium chloride in 1 M solutions were found to be equally effective in preventing alcohol injury with the same efficiency as 1 M sodium solutions of NAC and NAS, excluding the acetate portion of NAC and NAS as being of primary importance for protection to occur. Further study, using different concentrations of sodium chloride (i.e., 150-1,000 mM) revealed that the 1 M solution was most optimal in preventing alcohol injury. One molar sodium by itself and when administered as part of the NAC solution also prevented gastric injury by concentrated acid and base.(ABSTRACT TRUNCATED AT 250 WORDS)
N-乙酰半胱氨酸(NAC),以20%的溶液口服时,是一种有效的保护剂,可防止无水乙醇诱导的大鼠胃损伤。本研究旨在确定这种保护作用的介导方式。当发现N-乙酰丝氨酸(NAS)对酒精损伤同样具有保护作用时,NAC作为谷胱甘肽前体起作用的观点被排除。NAS分子在NAC含有巯基的位点含有一个羟基部分。为了在中性pH值下口服20%的NAC,需向游离酸形式中加入氢氧化钠以保持NAC溶解。我们通过滴定确定钠浓度为1.2M。因此,很明显NAC的保护作用可能是通过用于滴定NAC的钠来介导的。相应地,我们研究了各种钠盐,并评估了它们对酒精损伤的相对保护作用。发现1M溶液中的醋酸钠和氯化钠在预防酒精损伤方面同样有效,其效率与1M的NAC和NAS钠溶液相同,排除了NAC和NAS的醋酸盐部分对保护作用至关重要的可能性。使用不同浓度的氯化钠(即150 - 1000 mM)的进一步研究表明,1M溶液在预防酒精损伤方面最为理想。单独的1M钠以及作为NAC溶液一部分给药时,也能预防浓酸和浓碱引起的胃损伤。(摘要截取自250字)