Investigation of pharmacological responses to anti-diabetic drugs in female Spontaneously Diabetic Torii (SDT) fatty rats, a new nonalcoholic steatohepatitis (NASH) model
| Autor: | Takeshi Ohta, Tomoyuki Saito, Shinichi Kume, Tohru Matsui, Katsuhiro Miyajima, Yasufumi Toriniwa, Kinuko Uno, Takahisa Yamada, Tatsuya Maekawa, Yukihito Ishii |
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| Rok vydání: | 2018 |
| Předmět: |
medicine.medical_specialty
Cirrhosis medicine.medical_treatment SDT fatty rat Eating 03 medical and health sciences 0302 clinical medicine Laboratory Animal Science Non-alcoholic Fatty Liver Disease Fibrosis Internal medicine Hyperlipidemia medicine Animals Hypoglycemic Agents RNA Messenger Full Paper Pioglitazone General Veterinary business.industry Insulin NASH Lipid metabolism Organ Size medicine.disease Metformin Diet Rats Disease Models Animal Cholesterol Endocrinology 030220 oncology & carcinogenesis Female Thiazolidinediones 030211 gastroenterology & hepatology business Hepatic fibrosis medicine.drug |
| Zdroj: | The Journal of Veterinary Medical Science |
| ISSN: | 1347-7439 0916-7250 |
| DOI: | 10.1292/jvms.18-0119 |
| Popis: | Nonalcoholic steatohepatitis (NASH) is a progressive liver disease, and some patients develop hepatic cirrhosis/carcinoma. Animal models play key roles in the development of new therapies for NASH. In this study, the pharmacological effects of metformin and pioglitazone were investigated in female Spontaneously Diabetic Torii (SDT) fatty rats to verify the utility of this model. The anti-diabetic drugs were administered to SDT fatty rats fed a cholesterol-enriched diet from 4 to 25 weeks, and changes in food intake, body weight, and blood chemistry parameters were evaluated every 4 weeks. The hepatic lipid content, mRNA expression in relation to lipid synthesis, inflammation, and fibrosis, and histopathological analyses were performed at 25 weeks. Pioglitazone improved hyperglycemia, hyperlipidemia, and abnormalities in hepatic parameters. The insulin levels were lower than those in the control rats before 16 weeks. Plasma glucose levels in the metformin-treated rats were lower than those in the control rats, and plasma alanine aminotransferase levels temporarily decreased. The lipid content and some mRNA expression in relation to fibrosis in the liver decreased with pioglitazone treatment, and the mRNA expression of microsomal triglyceride transfer protein increased. Hepatic fibrosis observed in the SDT fatty rats improved with pioglitazone treatment; however, the effect with metformin treatment was partial. These results in both drugs are in line with results in the human study, suggesting that the SDT fatty rat is useful for developing new anti-NASH drugs that show potential to regulate glucose/lipid metabolism. |
| Databáze: | OpenAIRE |
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