RESUMEN
Background and purpose: 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. Experimental approach: 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. Conclusion and implications: 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.
RESUMEN
PURPOSE: Hepatic encephalopathy (HE) or hepatic coma is a demanding, not utterly understood complication of acute and chronic liver dysfunction and portosystemic shunting. In HE, hyperammonemia and inflammatory responses are believed to act in synergism. Probiotics, Lactobacillus plantarum UBLP40 and Bacillus clausii UBBC07 reduce small intestinal bacterial overgrowth and hyperammonemia, thereby preventing HE development. METHODS: The effect of probiotics-Lactobacillus plantarum UBLP40 (107 CFU/day, 14 days) and Bacillus clausii UBBC07 (107 CFU/day, 14 days) combination and standard drug-lactulose (2.5 ml/kg in 3 divided doses, 14 days) was studied in thioacetamide (250 mg/kg for three days) induced acute HE in rats by measuring behavioural parameters, biochemical parameters (serum AST, ALT, ALP and ammonia level), neurochemical parameters and histopathology study in brain and liver. RESULTS: In contrast to only thioacetamide treated rats, probiotics treatment substantially (p < 0.001) reduced liver function parameters, i.e. serum AST, ALT, ALP, and ammonia, improved behaviour parameters, i.e. decreased motor disruption, improved memory impairment. Probiotics treated rats have also shown a substantial improvement in oxidative stress parameters i.e. reduced lipid peroxidation and increased glutathione level in brain tissue and ameliorated the histopathological changes induced by thioacetamide in the brain and liver. CONCLUSIONS: It can be concluded based on the findings that the combination therapy of Lactobacillus plantarum UBLP40 and Bacillus clausiiUBBC07 proves to be effective in acute hepatic encephalopathy in the preclinical stage, and further studies are required to assess this therapy potential in the clinical setting.
