Dataset Information

Effect of antisense TGF-beta1 oligodeoxynucleotides in streptozotocin- induced diabetic rat kidney.

ABSTRACT: Transforming growth factor (TGF)-beta1 is an important fibrogenic factor that is involved in the pathogenesis of diabetic nephropathy. We evaluated the effect of circular antisense TGF-beta1 oligodeoxynucleotides (ODNs) on the TGF-beta1 expression in the rat mesangial cell culture and in streptozotocin (STZ)-induced diabetic rats. Circular antisense TGF-beta1 ODNs were found to be stable in rat serum, significantly decreasing TGF-beta1 mRNA expression compared with linear antisense ODNs in the rat mesangial cell culture. Circular antisense TGF-beta1 ODNs were introduced into the tail vein of normal rats using hemagglutinating virus of Japan (HVJ)-liposome-mediated gene transfer method and were confirmed to be delivered effectively into the kidney, liver, lungs, and spleen. To inhibit the overexpression of TGF-beta1 in diabetic kidneys, we introduced circular antisense TGF-beta1 ODNs into the STZ-induced diabetic rats. On day 13 after circular antisense TGF-beta1 ODNs injection, TGF-beta1 mRNA and protein expression markedly decreased and urinary TGF-beta1 excretion rate also dropped in the circular antisense TGF-beta1 ODNs-treated diabetic rats. These results suggest that circular antisense TGF-beta1 ODNs may be a useful tool for developing new therapeutic application for progressive diabetic nephropathy.

SUBMITTER: Jeong HS

PROVIDER: S-EPMC2816838 | biostudies-literature | 2004 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effect of antisense TGF-beta1 oligodeoxynucleotides in streptozotocin- induced diabetic rat kidney.

Jeong Hyo Soon HS Park Kwan Kyu KK Park Kwan Kyu KK Kim Sang Pyo SP Choi In Jang IJ Lee In Kyu IK Kim Hyun Chul HC

Journal of Korean medical science 20040601 3

Transforming growth factor (TGF)-beta1 is an important fibrogenic factor that is involved in the pathogenesis of diabetic nephropathy. We evaluated the effect of circular antisense TGF-beta1 oligodeoxynucleotides (ODNs) on the TGF-beta1 expression in the rat mesangial cell culture and in streptozotocin (STZ)-induced diabetic rats. Circular antisense TGF-beta1 ODNs were found to be stable in rat serum, significantly decreasing TGF-beta1 mRNA expression compared with linear antisense ODNs in the r ...[more]

PMID: 15201503

Similar Datasets

Project description:Background:Ceratonia siliqua pods (carob) have been nominated to control the high blood glucose of diabetics. In Yemen, however, its antihyperglycemic activity has not been yet assessed. Thus, this study evaluated the in vitro inhibitory effect of the methanolic extract of carob pods against ?-amylase and ?-glucosidase and the in vivo glycemic effect of such extract in streptozotocin-nicotinamide induced diabetic rats. Methods:2,2-diphenyl-1-picrylhydrazyl (DPPH) and Ferric reducing antioxidant power assay (FRAP) were applied to evaluate the antioxidant activity of carob. In vitro cytotoxicity of carob was conducted on human hepatocytes (WRL68) and rat pancreatic ?-cells (RIN-5F). Acute oral toxicity of carob was conducted on a total of 18 male and 18 female Sprague-Dawley (SD) rats, which were subdivided into three groups (n = 6), namely: high and low dose carob-treated (CS5000 and CS2000, respectively) as well as the normal control (NC) receiving a single oral dose of 5,000 mg kg-1 carob, 2,000 mg kg-1 carob and 5 mL kg-1 distilled water for 14 days, respectively. Alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, total bilirubin, creatinine and urea were assessed. Livers and kidneys were harvested for histopathology. In vitro inhibitory effect against ?-amylase and ?-glucosidase was evaluated. In vivo glycemic activity was conducted on 24 male SD rats which were previously intraperitoneally injected with 55 mg kg-1 streptozotocin (STZ) followed by 210 mg kg-1nicotinamide to induce type 2 diabetes mellitus. An extra non-injected group (n = 6) was added as a normal control (NC). The injected-rats were divided into four groups (n = 6), namely: diabetic control (D0), 5 mg kg-1glibenclamide-treated diabetic (GD), 500 mg kg-1 carob-treated diabetic (CS500) and 1,000 mg kg-1 carob-treated diabetic (CS1000). All groups received a single oral daily dose of their treatment for 4 weeks. Body weight, fasting blood glucose (FBG), oral glucose tolerance test, biochemistry, insulin and hemostatic model assessment were assessed. Pancreases was harvested for histopathology. Results:Carob demonstrated a FRAP value of 3191.67 ± 54.34 µmoL Fe++ and IC50 of DPPH of 11.23 ± 0.47 µg mL-1. In vitro, carob was non-toxic on hepatocytes and pancreatic ?-cells. In acute oral toxicity, liver and kidney functions and their histological sections showed no abnormalities. Carob exerted an in vitro inhibitory effect against ?-amylase and ?-glucosidase with IC50 of 92.99 ± 0.22 and 97.13 ± 4.11 µg mL-1, respectively. In diabetic induced rats, FBG of CS1000 was significantly less than diabetic control. Histological pancreatic sections of CS1000 showed less destruction of ?-cells than CS500 and diabetic control. Conclusion:Carob pod did not cause acute systemic toxicity and showed in vitro antioxidant effects. On the other hand, inhibiting ?-amylase and ?-glucosidase was evident. Interestingly, a high dose of carob exhibits an in vivo antihyperglycemic activity and warrants further in-depth study to identify the potential carob extract composition.

Dataset Information

Effect of antisense TGF-beta1 oligodeoxynucleotides in streptozotocin- induced diabetic rat kidney.

Publications

Effect of antisense TGF-beta1 oligodeoxynucleotides in streptozotocin- induced diabetic rat kidney.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets