ATORVASTATIN AND RIFAXIMIN IN THYROID PREVENT LIVER THYROID METABOLISM ABNORMALITIES IN HEPATOCELLULAR CARCINOMA: IN VITRO AND IN VIVO STUDY

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Metabolic-associated steatotic liver disease (MASLD) is one of the leading causes of hepatocellular carcinoma (HCC) worldwide. We evaluated tumoral processes and thyroid metabolism alterations in experimental HCC. Atorvastatin (AT) and Rifaximin (RIFA) were evaluated in vitro and in vivo. Huh7 cells were pretreated with AT (20µM) or RIFA (10µM), subsequently treated with endocrine disrupting tumor promoter (HCB5µM). Sprague-Dawley rats received diethylnitrosamine (135mg/l) in drinking water for 16 weeks, high-fat diet and AT (5mg/Kg) or RIFA (5ml/Kg). In vitro results revealed that HCB increased colony formation (39%), TGFB1 (45%), COX-2 (25%), cytochrome-c (35%) and caspase-3 (25%) compared to control (CON) - AT and RIFA prevent the increase. AT and RIFA also prevented T3 levels from decreasing. Animals showed 88% higher TGFB1 expression in tumoral areas compared with normal adjacent tissue. AT or RIFA diminished TGFB by 10 and 30% respectively. Fibrosis area was reduced with RIFA by 30%, compared to HCC. AT did not induce significant decrease. HIF1 augmented 200% in tumor areas while AT or RIFA diminished 75% and 50% respectively. DIO3 augmented by 50% in tumor and DIO1 expression did not change. In conclusion, tumor growth and dedifferentiation seem to diminish with AT or RIFA in both models. Thyroid hormone metabolism changes in different forms: in cells, T3 seems to be altered by D1 and in animals by D3 alterations. These differences can be due to diverse stages of tumor growth and aggressiveness in the models.

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