title: 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.
abstract: 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.
authors: Department of Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors: Takahiro
authors: T
authors: Kochi
authors: Masahito
authors: M
authors: Shimizu
authors: Daishi
authors: D
authors: Terakura
authors: Atsushi
authors: A
authors: Baba
authors: Tomohiko
authors: T
authors: Ohno
authors: Masaya
authors: M
authors: Kubota
authors: Yohei
authors: Y
authors: Shirakami
authors: Hisashi
authors: H
authors: Tsurumi
authors: Takuji
authors: T
authors: Tanaka
authors: Hisataka
authors: H
authors: Moriwaki
mesh_terms: D000804:Angiotensin II / Q000097:blood; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005234:Fatty Liver / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D015870:Gene Expression; D006973:Hypertension / Q000150:complications*; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D008113:Liver Neoplasms / Q000517:prevention & control*; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000150:complications*; D018384:Oxidative Stress; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D011230:Precancerous Conditions / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics
chemical_list: D016588:Anticarcinogenic Agents; D015850:Interleukin-6; D044140:Receptor, Angiotensin, Type 1; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D002392:Catechin; C045651:epigallocatechin gallate; D007703:Peptidyl-Dipeptidase A
keywords: EGCG; Hypertension; Liver fibrosis; Liver tumorigenesis; Obesity