Combining Sorafenib and Lactobacillus Rhamnosus Gg Reduces Liver Fibrosis and Hepatic Encephalopathy Following Bile Duct Ligation in Rats Publisher



Rahjoo T ; Ashabi G ; Adeli S ; Halimi S ; Panahi M ; Tamtaji O R ; Ghasemi Tarie R ; Nabavizadeh F
Source: Iranian Journal of Basic Medical Sciences Published:2026

Abstract

Objective(s): Liver fibrosis can progress to hepatic encephalopathy (HE). While sorafenib is a drug employed to treat liver fibrosis, its use is linked to drug resistance and adverse effects. We examined the potential benefits of combining sorafenib with the probiotic Lactobacillus rhamnosus GG (LGG) on liver fibrosis and HE in bile duct ligated (BDL) rats. Materials and Methods: Forty male rats were randomly assigned to five groups of eight rats each, including sham, BDL, BDL+probiotic (LGG, 1×109 CFU/ml/day), BDL+sorafenib (20 mg/kg), and BDL+probiotic+sorafenib. First, rats receive probiotic LGG or solvent for 2 weeks. Following a one-week post-BDL recovery period, the animals received sorafenib and probiotic LGG for three consecutive weeks. Next, various parameters were appraised. Results:The combination of sorafenib with LGG led to less liver fibrosis when compared with sorafenib alone. This combination therapy also alleviated inflammation and oxidative species present in the liver and frontal cortex. Further, this combination diminished hepatic Toll-like receptor 4/ Nuclear factor kappa-β expression. Finally, it led to improved cognitive function in behavioral assessments compared to using sorafenib alone. Conclusion: Overall, combining a low dose of sorafenib with probiotic LGG may offer significant benefits for treating liver fibrosis and HE. © 2026. This work is openly licensed via CC BY 4.0. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.