Bosentan ameliorates the expression of fibrotic related growth factors and collagen-1 in diabetic mice

Abstract

Objective: To investigate the potential beneficial effect of bosentan in ameliorating fibrotic agents in diabetic mice. Methods: Male 6-week old C57BL/6 mice were divided into 3 groups (N=20): Control group, diabetes mellitus (DM) group and DM-B group (diabetes with bosentan group). Streptozotocin (STZ) was injected as 200 mg/Kg for single dose, i.p. (intraperitoneal injection). Fasting blood glucose (FBG) was measured at 0-, 1-, 2-week after STZ injection to confirm that diabetes was induced in the mice. Bosentan (100mg/Kg) and placebo was given i.g. (intragastric administration) once a day immediately after STZ injection for 18 weeks. The mRNA expression of tissue growth factor beta (TGF-b), connective tissue growth factor (CTGF), vascular endothelial growth factor (VEGF) and collagen-1 were evaluated by RT-PCR and real-time PCR. Differences in the data between the groups were compared by Student t-test for independent samples. Results: After 18 weeks of diabetic situation, FBG of DM-B mice was significantly higher than that of control mice and was similar with that of DM mice (DM mice vs. control mice, p<0.001; DM-B vs. control mice, p<0.001; DM mice vs. DM-B mice, p>0.05). The cardiac VEGF mRNA (a potent angiogenic factor) level in DM-B mice was significantly higher than DM mice (p<0.01). The heart of DM-B mice also showed lower expression of fibrotic genes (TGF-b, CTGF and collagen-1) than DM mice (p<0.01). Conclusion: These findings indicate the potential usefulness of an ET receptor antagonist bosentan in the amelioration of fibrotic agents, which may promote tissue fibrosis. This may provide a promising therapeutical strategy for diabetic cardiac fibrosis.

Endothelin antagonists for diabetic and non‐diabetic chronic kidney disease

“…In general, ETA‐selective antagonists have consistently proven to improve renal function in various animal models of CKD. Some animal data have also shown that a non‐selective antagonist, such as bosentan, can produce beneficial effects in a diabetic kidney disease model . Saleh and colleagues directly compared a combined vs. ETA selective antagonist in the type 1 diabetic rat model and observed that while the ETA selective antagonist produced a more rapid decline in proteinuria, after 1 week treatment the decline in proteinuria was similar between the two types of antagonists .…”

Animal Models of Diabetes Mellitus for Islet Transplantation

“…For example, mice required higher doses of STZ for inducing DM compared with other animals. While in ICR mice DM can be induced with comparatively lower doses (90–150 mg/kg), C57BL/6 mice need approximately 200 mg/kg dose of STZ [40, 42–48]. Immunodeficient mice tend to need less dose of STZ than other wild-type strains.…”

The Modulative Effects of Microcurrent Electrical Nerve Stimulation on Diabetic Mice

“…After two weeks inductions, the GLU-AC was about 170 mg/dl which is more the previous DM GLU-AC criteria in ICR strain (20). The diabetes physiological features, such like GLU-AC became more severe (higher) over the time prolonged after STZ induction (36) and the GLU-AC also sub-stantially increase from 171 ± 12 mg/dl (the 3rd week after induction) to 373 ± 36 mg/dl (the 6th week after induction) (Fig. 4, A and B) which is consistent to previous report.…”