D-chiro-inositol effectively attenuates cholestasis in bile duct ligated rats by improving bile acid secretion and attenuating oxidative stress

Autor: Yi-Xuan Zhang, Xuefu You, Ge Maoxu, Li Naren, Zhao Shuangshuang, He Hongwei, Rong-Guang Shao, Hong Liu, Long-Yin Zhao, Wuli Zhao
Rok vydání: 2017
Předmět:
Liver Cirrhosis
Male
0301 basic medicine
Cirrhosis
medicine.medical_treatment
Gene Expression
Liver transplantation
Rats
Sprague-Dawley
Pharmacology (medical)
ATP Binding Cassette Transporter
Subfamily B
Member 11
Cholestasis
Bile acid
biology
Bile duct
NF-kappa B
Alanine Transaminase
Stereoisomerism
General Medicine
Polycystic ovary
medicine.anatomical_structure
Liver
Original Article
medicine.medical_specialty
medicine.drug_class
Antigens
Differentiation
Myelomonocytic
Protective Agents
digestive system
Bile Acids and Salts
03 medical and health sciences
Antigens
CD
Internal medicine
medicine
Animals
Aspartate Aminotransferases
Ligation
Pharmacology
Superoxide Dismutase
business.industry
medicine.disease
Bile duct proliferation
Disease Models
Animal
Oxidative Stress
030104 developmental biology
Endocrinology
Alanine transaminase
biology.protein
ATP-Binding Cassette Transporters
Bile Ducts
business
Inositol
Zdroj: Acta Pharmacologica Sinica. 39:213-221
ISSN: 1745-7254
1671-4083
DOI: 10.1038/aps.2017.98
Popis: Cholestatic liver diseases are important causes of liver cirrhosis and liver transplantation, but few drugs are available for treatment. D-chiro-inositol (DCI), an isomer of inositol found in many Leguminosae plants and in animal viscera, is used clinically for the treatment of polycystic ovary syndrome (PCOS) and diabetes mellitus. In this study, we investigated whether DCI exerted an anti-cholestatic effect and its underlying mechanisms. A cholestatic rat model was established via bile duct ligation (BDL). After the surgery, the rats were given DCI (150 mg·kg-1·d-1) in drinking water for 2 weeks. Oral administration of DCI significantly decreased the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and attenuated bile duct proliferation, parenchymal necrosis and fibrosis in BDL rats. Furthermore, DCI treatment significantly increased the serum and bile levels of total bile acid (TBA), and decreased TBA levels in the liver. Moreover, DCI treatment significantly increased expression of the genes encoding bile acid transporters BSEP (Abcb11) and MRP2 (Abcc2) in liver tissues. DCI treatment also markedly decreased hepatic CD68 and NF-kappaB (NF-κB) levels, significantly decreased the serum and hepatic MDA levels, markedly increased superoxide dismutase activity in both serum and liver tissues. Using whole-genome oligonucleotide microarray, we revealed that DCI treatment altered the expression profiles of oxidation reduction-related genes in liver tissues. Collectively, DCI effectively attenuates BDL-induced hepatic bile acid accumulation and decreases the severity of injury and fibrosis by improving bile acid secretion, repressing inflammation and decreasing oxidative stress. The results suggest that DCI might be beneficial for patients with cholestatic disorders.
Databáze: OpenAIRE
Externí odkaz: