Dimethyl sulfoxide inhibits bile acid synthesis in healthy mice but does not protect mice from bile-acid-induced liver damage

Authors: CHEN, XI - Children'S Nutrition Research Center (CNRC); LI, HUIQIAO - Children'S Nutrition Research Center (CNRC); LIU, YU'E - Tongji Medical College; QI, JING - Central South University; DONG, BINGNING - Baylor College Of Medicine; HUANG, SHIXIA - Baylor College Of Medicine; ZHAO, SHANGANG - University Of Texas Health Science Center; ZHU, YI - Children'S Nutrition Research Center (CNRC)

Submitted to: Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/7/2023
Publication Date: 8/9/2023
Citation: Chen, X., Li, H., Liu, Y., Qi, J., Dong, B., Huang, S., Zhao, S., Zhu, Y. 2023. Dimethyl sulfoxide inhibits bile acid synthesis in healthy mice but does not protect mice from bile-acid-induced liver damage. Biology. 12(8). Article 1105. https://doi.org/10.3390/biology12081105.
DOI: https://doi.org/10.3390/biology12081105

Interpretive Summary: Inhibiting bile acid synthesis is vital for patients with obstructed bile ducts. This paper uses mice as the research model and shows that dimethyl sulfoxide, a commonly used organic solvent, inhibits bile acid synthesis in healthy mice but does not protect mice from bile-acid-induced liver damage.

Technical Abstract: Bile acids serve a vital function in lipid digestion and absorption; however, their accumulation can precipitate liver damage. In our study, we probed the effects of dimethyl sulfoxide (DMSO) on bile acid synthesis and the ensuing liver damage in mice induced by bile acids. Our findings indicate that DMSO efficaciously curbs bile acid synthesis by inhibiting key enzymes involved in the biosynthetic pathway, both in cultured primary hepatocytes and in vivo. Contrarily, we observed that DMSO treatment did not confer protection against bile-acid-induced liver damage in two distinct mouse models: one induced by a 0.1% DDC diet, leading to bile duct obstruction, and another induced by a CDA-HFD, resulting in non-alcoholic steatohepatitis (NASH). Histopathological and biochemical analyses unveiled a comparable extent of liver injury and fibrosis levels in DMSO-treated mice, characterized by similar levels of increase in Col1a1 and Acta2 expression and equivalent total liver collagen levels. These results suggest that, while DMSO can promptly inhibit bile acid synthesis in healthy mice, compensatory mechanisms might rapidly override this effect, negating any protective impact against bile-acid-induced liver damage in mice. Through these findings, our study underscores the need to reconsider treating DMSO as a mere inert solvent and prompts further exploration to identify more effective therapeutic strategies for the prevention and treatment of bile-acid-associated liver diseases.