Apocynin and enzymatically modified isoquercitrin suppress the expression of a NADPH oxidase subunit p22phox in steatosis-related preneoplastic liver foci of rats

详细信息    查看全文

• 作者：Toshinori Yoshida^a ; ^{yoshida7@cc.tuat.ac.jp} ; Hirotada Murayama^a ; Masahi Kawashima^a ; Rei Nagahara^a ; Yumi Kangawa^a ; Sayaka Mizukami^a ; ^b ; Masayoshi Kimura^a ; ^b ; Hajime Abe^a ; ^b ; Shim-mo Hayashi^c ; Makoto Shibutani^a
• 关键词：NADPH oxidase ; Preneoplastic liver cell lesions ; Two-stage hepatocarcinogenesis model ; High fat diet ; Apocynin ; Enzymatically modified isoquercetin
• 刊名：Experimental and Toxicologic Pathology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：69
• 期：1
• 页码：9-16
• 全文大小：3172 K
• 卷排序：69

文摘

We determined effects of the NADPH oxidase (NOX) inhibitor apocynin (APO) or the antioxidant enzymatically modified isoquercitrin (EMIQ) on an early stage of hepatocarcinogenesis in the liver with steatosis. Male rats were given a single intraperitoneal injection of N-diethylnitrosamine (DEN) and fed a high-fat diet (HFD) to subject to a two-stage hepatocarcinogenesis model. Two weeks later, rats were fed a HFD containing the lipogenic substance malachite green (MG), which were co-administered with EMIQ or APO in drinking water for 6 weeks. Three after DEN initiation, rats were subjected to a two-third partial hepatectomy to enhance cell proliferation. The HFD increased total cholesterol and alkaline phosphatase levels, which were reduced by EMIQ co-administration. APO co-administration reduced MG-increased preneoplastic liver lesions, glutathione S-transferase placental form (GST-P)-positive, adipophilin-negative liver foci, and tended to decrease MG-increased Ki-67-positive or active caspase-3-positive cells in the liver foci. EMIQ or APO co-administration reduced the expression of a NOX subunit p22phox in the liver foci, but did not alter the numbers of LC3a-positive cells, an autophagy marker. We identified no treatment-related effects on p47phox and NOX4 expression in the liver foci. The results indicated that APO or EMIQ had the potential to suppress hyperlipidaemia and steatosis-preneoplastic liver lesions, through suppression of NOX subunit expression in rats.