Green tea extract protects against diethylnitrosamine-mediated liver injury and cell proliferation by attenuating STAT3 and iNOS expression in high fat-induced obese mice with nonalcoholic steatohepatitis
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2017
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ndltd-OhioLink-oai-etd.ohiolink.edu-osu15028989134217242021-08-03T07:03:46Z Green tea extract protects against diethylnitrosamine-mediated liver injury and cell proliferation by attenuating STAT3 and iNOS expression in high fat-induced obese mice with nonalcoholic steatohepatitis Kim, Joshua B. Nutrition diethylnitrosamine green tea hepatocellular carcinoma nonalcoholic steatohepatitis obesity Nonalcoholic steatohepatitis (NASH) increases hepatocellular carcinoma (HCC) risk by increasing inflammation and oncogenesis. Antiinflammatory activities of green tea extract (GTE) protect against dietary high-fat (HF)-induced NASH. I hypothesized that antiinflammatory and anti-oncogenic activities of GTE during NASH would also prevent diethylnitrosamine (DEN)-induced development towards HCC. Male C57BL/6J mice (4 wk old) were fed a HF diet devoid of, or supplemented with, GTE at 2% (w/w) and received once weekly intraperitoneal injections of saline vehicle or DEN (60 mg/kg; 5 and 7 wk old) until 25 wk old. Gross pathological observation indicated no tumors, as expected. GTE protected against obesity-associated parameters, histological and biochemical evidence of NASH, and hepatic TNFa and MCP-1 expression in both saline- and DEN-injected mice (P<0.05). GTE attenuated serum alanine aminotransferase (ALT) activity, hepatic malondialdehyde (MDA), hepatic iNOS and survivin mRNA expression, signal transducer and activator of transcription 3 (STAT3), and hepatocyte proliferating cell nuclear antigen (PCNA) otherwise exacerbated by DEN. Hepatic GSTP protein expression increased in mice fed GTE. Serum ALT was correlated (r = 0.71-0.83; P<0.0001) with MDA, iNOS, STAT3, survivin and PCNA. iNOS correlated with PCNA, STAT3 (r = 0.64-0.65; P<0.05) and survivin (r = 0.66; P<0.0001), suggesting that iNOS-induced inflammation regulates liver injury and oncogenic cell proliferation. GTE lowers NASH- and DEN-mediated HCC risk by increasing GSTP and attenuating iNOS-mediated liver injury and survivin-mediated cell proliferation. 2017 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1502898913421724 http://rave.ohiolink.edu/etdc/view?acc_num=osu1502898913421724 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
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English |
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Nutrition diethylnitrosamine green tea hepatocellular carcinoma nonalcoholic steatohepatitis obesity |
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Nutrition diethylnitrosamine green tea hepatocellular carcinoma nonalcoholic steatohepatitis obesity Kim, Joshua B. Green tea extract protects against diethylnitrosamine-mediated liver injury and cell proliferation by attenuating STAT3 and iNOS expression in high fat-induced obese mice with nonalcoholic steatohepatitis |
author |
Kim, Joshua B. |
author_facet |
Kim, Joshua B. |
author_sort |
Kim, Joshua B. |
title |
Green tea extract protects against diethylnitrosamine-mediated liver injury and cell proliferation by attenuating STAT3 and iNOS expression in high fat-induced obese mice with nonalcoholic steatohepatitis |
title_short |
Green tea extract protects against diethylnitrosamine-mediated liver injury and cell proliferation by attenuating STAT3 and iNOS expression in high fat-induced obese mice with nonalcoholic steatohepatitis |
title_full |
Green tea extract protects against diethylnitrosamine-mediated liver injury and cell proliferation by attenuating STAT3 and iNOS expression in high fat-induced obese mice with nonalcoholic steatohepatitis |
title_fullStr |
Green tea extract protects against diethylnitrosamine-mediated liver injury and cell proliferation by attenuating STAT3 and iNOS expression in high fat-induced obese mice with nonalcoholic steatohepatitis |
title_full_unstemmed |
Green tea extract protects against diethylnitrosamine-mediated liver injury and cell proliferation by attenuating STAT3 and iNOS expression in high fat-induced obese mice with nonalcoholic steatohepatitis |
title_sort |
green tea extract protects against diethylnitrosamine-mediated liver injury and cell proliferation by attenuating stat3 and inos expression in high fat-induced obese mice with nonalcoholic steatohepatitis |
publisher |
The Ohio State University / OhioLINK |
publishDate |
2017 |
url |
http://rave.ohiolink.edu/etdc/view?acc_num=osu1502898913421724 |
work_keys_str_mv |
AT kimjoshuab greenteaextractprotectsagainstdiethylnitrosaminemediatedliverinjuryandcellproliferationbyattenuatingstat3andinosexpressioninhighfatinducedobesemicewithnonalcoholicsteatohepatitis |
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