Patel Chirag, Shahgond Lalita, Acharya Sanjeev, Boddu Sai Hs, Ranch Ketan
Department of Pharmacology, LM College of Pharmacy, Ahmedabad, India.
Department of Pharmacology, SSR College of Pharmacy, Silvassa, Dadra, and Nagar Haveli, India.
Res Pharm Sci. 2022 Jul 14;17(4):445-456. doi: 10.4103/1735-5362.350244. eCollection 2022 Aug.
Hepatic encephalopathy (HE) is a brain dysfunction caused by acute and chronic hepatic failure. The pathogenesis of HE is unknown, although small intestinal bacterial overgrowth associated with chronic liver damage, hyperammonemia, and oxidative stress are considered major factors for HE. Effective lowering of circulating ammonia and neuroinflammation is the main strategy for preventing and treating HE in cirrhosis. In the present study, the protective effect of probiotics (Lactobacillus plantarum and Bacillus clausii) and ascorbic acid in combination was assessed in bile duct ligation (BDL)-induced chronic HE in rats.
Sprague Dawley rats were divided into five groups (n = 6). All groups were subjected to double ligation of the bile duct and fed a hyperammonemia diet, except group I (normal control). Groups III and IV were treated with a low and high dose of combination therapy, respectively, while group V was given lactulose. Four weeks post ligation, behavioral, biochemical, and neurochemical parameters were measured. The liver and brain were dissected for histopathology and protein analyses.
FINDINGS / RESULTS: Combination therapy reduced plasma AST, ALT, ALP, and ammonia levels and attenuated hepatic inflammation/fibrosis in cirrhotic rats. Furthermore, combination therapy significantly improved behavioral parameters and restored the antioxidant enzyme activity. Histological changes were observed in the brain and liver of BDL animals.
The additive impact of probiotics and ascorbic acid on BDL-induced chronic HE in rats was mediated by a reduction in ammonia and oxidative stress, implying the therapeutic potential of combination therapy in HE.
肝性脑病（HE）是一种由急性和慢性肝衰竭引起的脑功能障碍。尽管与慢性肝损伤相关的小肠细菌过度生长、高氨血症和氧化应激被认为是HE的主要因素，但HE的发病机制尚不清楚。有效降低循环氨水平和神经炎症是预防和治疗肝硬化患者HE的主要策略。在本研究中，评估了益生菌（植物乳杆菌和克劳氏芽孢杆菌）与抗坏血酸联合使用对胆管结扎（BDL）诱导的大鼠慢性HE的保护作用。
将Sprague Dawley大鼠分为五组（n = 6）。除I组（正常对照组）外，所有组均进行胆管双重结扎并给予高氨血症饮食。III组和IV组分别接受低剂量和高剂量的联合治疗，而V组给予乳果糖。结扎四周后，测量行为、生化和神经化学参数。解剖肝脏和大脑进行组织病理学和蛋白质分析。
联合治疗降低了肝硬化大鼠的血浆AST、ALT、ALP和氨水平，并减轻了肝脏炎症/纤维化。此外，联合治疗显著改善了行为参数并恢复了抗氧化酶活性。在BDL动物的大脑和肝脏中观察到了组织学变化。
益生菌和抗坏血酸对BDL诱导的大鼠慢性HE的附加作用是通过降低氨和氧化应激介导的，这意味着联合治疗在HE中的治疗潜力。
