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4mu Supplement – Does it Reduce Liver Tumors and Hepatic Inflammation?

4mu supplement is a bile acid sequestrant and is clinically used in bile spasm treatment. It also attenuates cancer metastasis in preclinical models by inhibiting hyaluronan (HA) synthesis via downregulation of HA synthases and depletion of UDP-glucuronic acid, which is a cofactor for HA synthesis. This study shows that oral administration of 4MU to 9 month old WT and HBV-TG mice results in significant reduction of liver tumors and hepatic nodules, as well as decreased hepatic inflammatory infiltrates. The effect on tumor growth was found to be dose-dependent and lasted until euthanasia of the mice.

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In the behavioral tests, the rotarod test was performed to assess motor functions and the forelimb grip strength test was done to evaluate neuromuscular functions. Both tests showed no significant difference between the groups after 10 weeks of 4MU treatment, but a positive trend was observed in the 4MU group when compared to the placebo group after 9 weeks of washout.

Liver metabolites, glucose and protein were measured in urine samples collected every three weeks throughout the study period. A significant increase in urinary protein concentrations, referred to as proteinuria, was observed in both the 4MU-treated and washout groups compared to placebo controls in week 4. In week 10, both the 4MU-treated and the placebo group showed protein levels outside normal physiological values.

Histochemical analysis of hepatic slices from the different treated groups showed that 4MU reduced fibrosis and necrosis and increased ECM proteins such as Fsp1. In addition, the expression of CSC markers such as CD133 was significantly decreased in the 4MU-treated group, which is associated with epithelial-mesenchymal transition (EMT). This effect of 4MU was found to be enhanced by the TMZ treatment.