Abstract
BackgroundThe cholesterol gallstones diseases (CGD) is highly correlated with metabolic syndrome and type 2 diabetes. The present study aimed to investigate preventive effects of pioglitazone (PIO), an antidiabetic drug, on the CGD in guinea pigs fed with a lithogenic diet (LD).MethodsThe guinea pigs were fed with the LD for 8 weeks. All guinea pigs were grouped as follows: low fat diet; LD; LD plus PIO (4 mg/kg); LD plus PIO (8 mg/kg); LD plus ezetimibe (EZE) (2 mg/kg). Gallbladder stones were observed using microscopy. The profile of biliary composition, and blood glucose, insulin and lipid were analyzed. The liver or ileum was harvested for determinations of hydroxyl-methyl-glutaryl-CoA reductase (HMGCR), sterol regulatory element-binding proteins 2 (SREBP2), 7α-hydroxylase (CYP7A1), adenosine triphosphate-binding cassette (ABC) sterol transporters G5 and G8 (ABCG5, ABCG8), bile salt export pump (BSEP), Niemann-Pick C1-Like 1 (NPC1L1) and acetyl-coenzyme A cholesterol acyltransferase (ACAT2) by Western blot. The gallbladders were used for histological examination.ResultsThe LD successfully induced gallstone. Both pioglitazone and ezetimibe prevented gallstone formation, as well as hepatic and cholecystic damages. Pioglitazone significantly decreased HMGCR and SREBP2, but increased CYP7A1, ABCG5, ABCG8, and BSEP in the liver. Pioglitazone also remarkably decreased NPC1L1 and ACAT2, while increased ABCG5/8 in the intestine. The beneficial alterations of cholesterol and bile acids in the bile, as well as profile of glucose, insulin and lipid in the blood were found in the guinea pigs treated with pioglitazone.ConclusionPioglitazone has a noticeable benefit towards the CGD, which is involved in changes of synthesis, transformation, absorption, and transportation of cholesterol.
Highlights
Cholesterol gallstone disease (CGD) is one of the most prevalent and costly diseases
Pioglitazone treatment inhibits cholesterol gallstone formation in the Guinea pigs fed with lithogenic diet (LD) In our study, the CTRL group had a cholesterol gallstone formation rate of 9.1%, the LD group showed a cholesterol gallstone formation rate of 85.7%, a statistically significant increase over the rate of the CTRL group
The present study clearly indicated that pharmacological treatment with pioglitazone effectively prevented the formation of cholesterol gallstones diseases (CGD) induced by the LD in guinea pigs, accompanied by decreased CH, increased bile acid (BA), and lower CH saturation index (CSI) in the bile as well as lower blood glucose, insulin, TG and CH levels
Summary
Cholesterol gallstone disease (CGD) is one of the most prevalent and costly diseases. High calorie diet, hyperinsulinism and metabolic syndrome are among the preeminent risk factors for developing CGD [1]. Precipitation of excess cholesterol in bile as solid crystals is a prerequisite for cholesterol gallstone formation. Novel approaches against these pathogenetic factors are urgently needed to be developed for the prevention and treatment of the CGD. The cholesterol gallstones diseases (CGD) is highly correlated with metabolic syndrome and type 2 diabetes. The present study aimed to investigate preventive effects of pioglitazone (PIO), an antidiabetic drug, on the CGD in guinea pigs fed with a lithogenic diet (LD)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
