Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, El-Minia, Egypt.
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia.
J Biochem Mol Toxicol. 2023 Nov;37(11):e23479. doi: 10.1002/jbt.23479. Epub 2023 Jul 23.
Gastric ulcer is a common disease with increased prevalence in the aged population. Aged gastric mucosa has increased susceptibility to injury along with nonsteroidal anti-inflammatory drugs use due to impaired mucosal defense and decreased vasodilator release. We investigated whether l-arginine could protect against age-related gastric ulceration induced by indomethacin. Aged and adult male Wistar rats were administered sole and combined treatment of l-arginine and N -nitro-l-arginine methyl ester ( l-NAME) before induction of gastric ulceration by indomethacin. The gastroprotective effect of l-arginine was displayed only in adult rats with indomethacin-induced gastric ulceration, as evidenced by a significant decrease in ulcer index, oxidative stress parameters, and mucosal myeloperoxidase activity along with increased mucosal PGE2 levels. Interestingly, the mucosal gene expressions of NF-кB, iNOS, and COX-2 were significantly suppressed by l-arginine pretreatment and aggregated upon pretreatment with l-NAME in both adult and aged rats treated with indomethacin. In conclusion, l-arginine protected the rats' gastric mucosa against indomethacin-induced gastric ulceration, possibly, at least in part, by enhancement of mucosal nitric oxide/PGE2 content along with suppressing gastric inflammation and oxidative stress. This study supposed that the gastroprotective effect of l-arginine depends on aging, and even so, the adoption of a new approach to gastric ulcer treatment for the aged population is warranted.
胃溃疡是一种常见疾病，在老年人群中的发病率增加。由于黏膜防御功能受损和血管扩张剂释放减少，老年胃黏膜对损伤的敏感性增加，加上非甾体抗炎药的使用。我们研究了 l-精氨酸是否可以预防吲哚美辛引起的与年龄相关的胃溃疡。在诱导吲哚美辛引起胃溃疡之前，给予雄性 Wistar 大鼠单独和联合给予 l-精氨酸和 N-硝基-l-精氨酸甲酯（l-NAME）治疗。l-精氨酸的胃保护作用仅在吲哚美辛诱导的胃溃疡的成年大鼠中表现出来，这表现在溃疡指数、氧化应激参数和黏膜髓过氧化物酶活性显著降低，同时黏膜 PGE2 水平增加。有趣的是，l-精氨酸预处理可显著抑制黏膜基因表达 NF-кB、iNOS 和 COX-2，并在给予吲哚美辛的成年和老年大鼠中聚集预处理 l-NAME。总之，l-精氨酸通过增强黏膜一氧化氮/PGE2 含量，同时抑制胃炎症和氧化应激，保护大鼠胃黏膜免受吲哚美辛引起的胃溃疡。这项研究表明，l-精氨酸的胃保护作用取决于年龄，即使如此，也有必要为老年人群采用一种新的胃溃疡治疗方法。
