title: Apocynin and enzymatically modified isoquercitrin suppress the expression of a NADPH oxidase subunit p22phox in steatosis-related preneoplastic liver foci of rats.
abstract: 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.
authors: Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan. Electronic address: yoshida7@cc.tuat.ac.jp.
authors: Toshinori
authors: T
authors: Yoshida
authors: Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan.
authors: Hirotada
authors: H
authors: Murayama
authors: Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan.
authors: Masahi
authors: M
authors: Kawashima
authors: Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan.
authors: Rei
authors: R
authors: Nagahara
authors: Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan.
authors: Yumi
authors: Y
authors: Kangawa
authors: Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan; Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan.
authors: Sayaka
authors: S
authors: Mizukami
authors: Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan; Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan.
authors: Masayoshi
authors: M
authors: Kimura
authors: Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan; Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan.
authors: Hajime
authors: H
authors: Abe
authors: Global Scientific and Regulatory Affairs, San-Ei Gen F.F.I., Inc., 1-1-11 Sanwa-cho, Toyonaka, Osaka 561-8588, Japan.
authors: Shim-Mo
authors: SM
authors: Hayashi
authors: Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan.
authors: Makoto
authors: M
authors: Shibutani
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D063646:Carcinogenesis / Q000139:chemically induced; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005234:Fatty Liver / Q000201:enzymology* / Q000473:pathology; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D019255:NADPH Oxidases / Q000096:biosynthesis*; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D000098:Acetophenones; D004791:Enzyme Inhibitors; C016527:isoquercitrin; D011794:Quercetin; C056165:acetovanillone; D019255:NADPH Oxidases; C515768:Cyba protein, rat
keywords: Apocynin; Enzymatically modified isoquercetin; High fat diet; NADPH oxidase; Preneoplastic liver cell lesions; Two-stage hepatocarcinogenesis model