Protective effect of probiotics and ascorbic acid on bile duct ligation- induced chronic hepatic encephalopathy in rats

Abstract

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.

Gut microbiome-brain-cirrhosis axis

“…[127] This model also results in changes to the gut microbiome. [128,129] Rats [130,131] and mice [132] given probiotic treatment to correct dysbiosis induced by BDL showed improvements in liver inflammatory markers and circulating ammonia levels, as well as neuropsychiatric symptoms associated with cirrhosis, such as object discrimination and motor balance. [131] Rats were also used as a model of FMT after BDL in a 2021 study.…”

“…[128,129] Rats [130,131] and mice [132] given probiotic treatment to correct dysbiosis induced by BDL showed improvements in liver inflammatory markers and circulating ammonia levels, as well as neuropsychiatric symptoms associated with cirrhosis, such as object discrimination and motor balance. [131] Rats were also used as a model of FMT after BDL in a 2021 study. These series of experiments showed that FMT from healthy rats, to rats that received BDL, resulted in reduced hypertension and alleviation of gut dysbiosis but did not significantly impact hepatic fibrosis or expression of liver inflammatory markers [133] (Table 1).…”

Oleuropein can Protect the Brain Against Deleterious Effects of Bile Duct Ligation in Male Mice

“…There is no definitive cure for this disease, and finding effective substances to prevent neuronal damage is significant. Antioxidant compounds such as gallic acid, naringenin, melatonin, and ascorbic acid have been essential in reducing brain damage caused by BDL [10][11][12]. Oleuropein (OP) is a flavonoid compound extracted from olive leaves and fruit, which has antioxidant and anti-inflammatory properties and can help prevent oxidative injuries [13].…”