Combining sorafenib and Lactobacillus rhamnosus GG reduces liver fibrosis and hepatic encephalopathy following bile duct ligation in rats

Articles in Press

Document Type : Original Article

Authors

1 Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

4 Department of Pathology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran

10.22038/ijbms.2026.91566.19763

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.

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 17 March 2026

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