title: Gossypol ameliorates liver fibrosis in diabetic rats induced by high-fat diet and streptozocin.
abstract: 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitors have been shown to treat type 2 diabetes (T2D). Since gossypol is an 11β-HSD1 inhibitor, the objective of the present study was to treat T2D and T2D-related liver fibrosis in rat model using low-dose gossypol. T2D was induced by feeding with high fat diet plus injection of streptozocin (30mg/kg). Diabetic rats were treated with either vehicle control or racemic gossypol with a dose of 15mg/kg/day for 4weeks followed by 15mg/kg/week for additional 8weeks. Blood glucose, cholesterol, LDL, and triglycerides were measured. Messenger mRNA levels of glucocorticoid receptor (Nr3c1), phosphoenolpyruvate carboxykinase (Pck1), glucose-6-phosphatase (G6pc), collagen I (Col1a1), collagen III (Col3a1), fibronectin (Fn1), tissue inhibitor of metalloproteinase 1 (Timp1), and 2 (Timp2) were measured. T2D rats had higher serum glucose, cholesterol, LDL, and triglyceride levels compared to control. Liver Nr3c1, Col1a1, Col3a1, Fn1, Timp1, and Timp2 were increased in T2D rats. T2D liver showed significant fibrosis with the increases of α-smooth muscle actin and fibronectin. After gossypol treatment, serum glucose level was lowered by 64%. Liver fibrosis was significantly ameliorated. Nr3c1, Col1a1, Col3a1, Fn1, Timp1, Timp2, Pck1 as well as G6pc levels were significantly reduced. In conclusion, low dose gossypol is effective for the treatment of T2D and T2D-related fibrosis.
authors.affiliation: Institute of Cancer Research, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, PR China.
authors.forename: Guorong
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR China.
authors.forename: Hanbin
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR China.
authors.forename: Ren-Shan
authors.initials: RS
authors.lastname: Ge
authors.affiliation: Institute of Cancer Research, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, PR China. Electronic address: wangyili@mail.xjtu.edu.cn.
authors.forename: Yili
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology*; D059305:Diet, High-Fat / Q000009:adverse effects*; D006072:Gossypol / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
chemical_list: D013311:Streptozocin; D006072:Gossypol
keywords: 11β-hydroxysteroid dehydrogenase; Diabetes type 2; Gossypol; High fat diet; Liver fibrosis