Yadav Sudhir K, Adhikary Biplab, Maity Biswanath, Bandyopadhyay Sandip K, Chattopadhyay Subrata
Department of Biochemistry, Dr. B.C. Roy Post Graduate Institute of Basic Medical Sciences, Kolkata, India.
Eur J Pharmacol. 2009 Jul 1;614(1-3):106-13. doi: 10.1016/j.ejphar.2009.04.046. Epub 2009 May 3.
The role of the ariginine-metabolism in the healing action of the Piper betle phenol, allylpyrocatechol (APC) and omeprazole against indomethacin-induced stomach ulceration in mouse was investigated. Indomethacin (18 mg/kg) was found to induce maximum stomach ulceration in Swiss albino mice on the 3rd day of its administration, which was associated with reduced arginase activity (21.6%, P<0.05), endothelial nitric oxide synthase (eNOS) expression (72%, P<0.001), and IL-4 and TGF-beta levels, along with increased inducible nitric oxide synthase (iNOS) (9.3 folds, P<0.001) expression, nitrite (2.29 folds, P<0.001), IL-1beta and IL-6 generation. Besides providing comparable healing as omeprazole (3 mg/kg x 3 days), APC (5 mg/kg x 3 days) shifted the iNOS/NO axis to the arginase/polyamine axis as revealed from the increased arginase activity (73.1%, P<0.001), eNOS expression (67.8%, P<0.001), and reduced iNOS expression (65.6%, P<0.001) and nitrite level (53.2%, P<0.001). These can be attributed to a favourable anti-/pro-inflammatory cytokines ratio, generated by APC. The healing by omeprazole was however, not significantly associated with those parameters.
研究了精氨酸代谢在胡椒酚、烯丙基邻苯二酚(APC)和奥美拉唑对吲哚美辛诱导的小鼠胃溃疡愈合作用中的作用。发现吲哚美辛(18 mg/kg)在给药第3天可诱导瑞士白化小鼠出现最大程度的胃溃疡,这与精氨酸酶活性降低(21.6%,P<0.05)、内皮型一氧化氮合酶(eNOS)表达降低(72%,P<0.001)、IL-4和转化生长因子-β水平降低以及诱导型一氧化氮合酶(iNOS)表达增加(9.3倍,P<0.001)、亚硝酸盐水平增加(2.29倍,P<0.001)、IL-1β和IL-6生成增加有关。除了提供与奥美拉唑(3 mg/kg×3天)相当的愈合效果外,APC(5 mg/kg×3天)将iNOS/NO轴转变为精氨酸酶/多胺轴,这从精氨酸酶活性增加(73.1%,P<0.001)、eNOS表达增加(67.8%,P<0.001)、iNOS表达降低(65.6%,P<0.001)和亚硝酸盐水平降低(53.2%,P<0.001)可以看出。这些可归因于APC产生的有利的抗炎/促炎细胞因子比例。然而,奥美拉唑的愈合作用与这些参数没有显著相关性。