Pharmacology Department, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Cairo, Egypt.
Pathology Department, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
Environ Sci Pollut Res Int. 2023 Jul;30(35):84791-84804. doi: 10.1007/s11356-023-28184-7. Epub 2023 Jun 28.
The aim of the present study was to investigate the impact of arginine (ARG), a nitric oxide (NO) precursor, on thioacetamide (TAA)-induced hepatic encephalopathy (HE) in rats by injection of TAA (100 mg/kg, i.p) three times per week for six consecutive weeks. TAA-injected rats were administered ARG (100 mg/kg; p.o.) concurrently with TAA for the six consecutive weeks. Blood samples were withdrawn, and rats were sacrificed; liver and brain tissues were isolated. Results of the present study demonstrated that ARG administration to TAA-injected rats revealed a restoration in the serum and brain ammonia levels as well as serum aspartate transaminase, alanine transaminase, and alkaline phosphatase and total bilirubin levels as well as behavioral alterations evidenced by restoration in locomotor activity, motor skill performance, and memory impairment. ARG showed also improvement in the hepatic and neuro-biochemical values, pro-inflammatory cytokines, and oxidative stress biomarkers. All these results were confirmed by histopathological evaluation as well as ultrastructural imaging of the cerebellum using a transmission electron microscope. Furthermore, treatment with ARG could ameliorate the immunological reactivity of nuclear factor erythroid-2-related factor 2 (Nrf2) and cleaved caspase-3 proteins in the cerebellum and hepatic tissues. From all the previous results, it can be fulfilled that ARG showed a beneficial role in modulating the adverse complications associated with TAA-induced HE in rats via reducing hyperammonemia and downregulating nuclear factor kappa B (NF-κB)-mediated apoptosis.
本研究旨在通过每周三次腹腔注射硫代乙酰胺（TAA）（100mg/kg）连续 6 周，研究精氨酸（ARG），一种一氧化氮（NO）前体，对大鼠 TAA 诱导的肝性脑病（HE）的影响。TAA 注射大鼠同时给予 ARG（100mg/kg；po）连续 6 周。采集血样，处死大鼠，分离肝脏和脑组织。本研究结果表明，ARG 给药可恢复 TAA 注射大鼠的血清和脑中氨水平，以及血清天冬氨酸转氨酶、丙氨酸转氨酶、碱性磷酸酶和总胆红素水平，恢复运动活性、运动技能表现和记忆障碍等行为改变。ARG 还改善了肝和神经生物化学值、促炎细胞因子和氧化应激生物标志物。所有这些结果都通过组织病理学评估以及使用透射电子显微镜对小脑进行超微结构成像得到证实。此外，ARG 治疗可改善小脑和肝组织中核因子红细胞 2 相关因子 2（Nrf2）和裂解半胱氨酸天冬氨酸蛋白酶 3 蛋白的免疫反应性。根据所有上述结果，可以得出结论，ARG 通过降低高氨血症和下调核因子 kappa B（NF-κB）介导的细胞凋亡，在调节 TAA 诱导的 HE 大鼠的不良并发症方面发挥有益作用。
