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Gallstone disease (GD) is highly correlated with metabolic syndrome and its related illnesses including type II diabetes (DMII) and polycystic ovary syndrome (PCOS). While previous studies claimed that metformin decreases the chance of developing GD in PCOS patients, this phenomenon has not been investigated in animal models to date.Here we fed a high fat diet (HFD) containing 2% of cholesterol and 1% of cholic acid to ten-week-old male C57Bl/6 mice for 105 days. The groups were as follows: Low fat diet; HFD; HFD + Ursodeoxycholic acid (UDCA) (day 1–105); HFD + Metformin (day 1–105); HFD + Metformin (Met) (day 64–105). All drugs were administered by oral gavage (Met = 300 mg/kg & UDCA = 750 mg/kg). Serum lipid profile and gross organ examination were performed after euthanasia. A microscopic evaluation of the paraffin-embedded gallbladders was done after hematoxylin & eosin and Von Kossa staining.HFD successfully induces gallstone (4 out of 4 of the HFD members). While both UDCA and metformin (d 1–105) prevented gallstone formation and cholecystitis, Metformin (d 64–105) group had a few small stones. Additionally, metformin induces mucosal calcification in gallbladder (porcelain GB) of more than 80% of the HFD + Met (day 1–105) and HFD + Met (day 64–105) groups, collectively, which can be a potential problem by itself.While metformin shows a noticeable benefit towards GB health by reducing the chance for gallstone formation, if it induces porcelain gallbladder in humans as well, it might inflict patients with preventable medical charges.