Non-alcoholic steatohepatitis and preneoplastic lesions develop in the liver of obese and hypertensive rats: Suppressing effects of EGCG on the development of liver lesions
| Autor: | Masaya Kubota, Masahito Shimizu, Atsushi Baba, Hisashi Tsurumi, Hisataka Moriwaki, Daishi Terakura, Takahiro Kochi, Tomohiko Ohno, Yohei Shirakami, Takuji Tanaka |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Liver Cirrhosis
Male Cancer Research medicine.medical_specialty Gene Expression Inflammation Peptidyl-Dipeptidase A medicine.disease_cause Rats Inbred WKY Catechin Receptor Angiotensin Type 1 Insulin resistance Non-alcoholic Fatty Liver Disease Fibrosis Rats Inbred SHR Internal medicine medicine Animals Anticarcinogenic Agents Obesity Interleukin-6 Tumor Necrosis Factor-alpha business.industry Angiotensin II Liver Neoplasms Fatty liver medicine.disease Rats Fatty Liver Oxidative Stress Endocrinology Liver Oncology Hypertension Lipid Peroxidation Steatosis Steatohepatitis medicine.symptom Liver cancer business Precancerous Conditions Oxidative stress |
| Zdroj: | Cancer Letters. 342:60-69 |
| ISSN: | 0304-3835 |
| Popis: | Non-alcoholic steatohepatitis (NASH), which involves hepatic inflammation and fibrosis, is associated with liver carcinogenesis. The activation of the renin-angiotensin system (RAS), which plays a key role in blood pressure regulation, promotes hepatic fibrogenesis. In this study, we investigated the effects of (-)-epigallocatechin-3-gallate (EGCG), a major component of green tea catechins, on the development of glutathione S-transferase placental form (GST-P)-positive (GST-P(+)) foci, a hepatic preneoplastic lesion, in SHRSP.Z-Lepr(fa)/IzmDmcr (SHRSP-ZF) obese and hypertensive rats. Male 7-week-old SHRSP-ZF rats and control non-obese and normotensive WKY rats were fed a high fat diet and received intraperitoneal injections of carbon tetrachloride twice a week for 8weeks. The rats were also provided tap water containing 0.1% EGCG during the experiment. SHRSP-ZF rats presented with obesity, insulin resistance, dyslipidemia, an imbalance of adipokines in the serum, and hepatic steatosis. The development of GST-P(+) foci and liver fibrosis was markedly accelerated in SHRSP-ZF rats compared to that in control rats. Additionally, in SHRSP-ZF rats, RAS was activated and inflammation and oxidative stress were induced. Administration of EGCG, however, inhibited the development of hepatic premalignant lesions by improving liver fibrosis, inhibiting RAS activation, and attenuating inflammation and oxidative stress in SHRSP-ZF rats. In conclusion, obese and hypertensive SHRSP-ZF rats treated with a high fat diet and carbon tetrachloride displayed the histopathological and pathophysiological characteristics of NASH and developed GST-P(+) foci hepatic premalignant lesions, suggesting the model might be useful for the evaluation of NASH-related liver tumorigenesis. EGCG might also be able to prevent NASH-related liver fibrosis and tumorigenesis. |
| Databáze: | OpenAIRE |
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