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

• Published in: Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie Vol. 69; no. 1; pp. 9 - 16
• Main Authors: Yoshida, Toshinori, Murayama, Hirotada, Kawashima, Masahi, Nagahara, Rei, Kangawa, Yumi, Mizukami, Sayaka, Kimura, Masayoshi, Abe, Hajime, Hayashi, Shim-mo, Shibutani, Makoto
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.01.2017
• Subjects: Acetophenones - pharmacology; alkaline phosphatase; Animals; antioxidants; Apocynin; autophagy; Carcinogenesis - chemically induced; cell proliferation; cholesterol; Disease Models, Animal; drinking water; Enzymatically modified isoquercetin; Enzyme Inhibitors - pharmacology; fatty liver; Fatty Liver - enzymology; Fatty Liver - pathology; glutathione transferase; hepatocytes; High fat diet; hyperlipidemia; Immunohistochemistry; intraperitoneal injection; isoquercitrin; liver; Liver - drug effects; Liver - enzymology; Liver Neoplasms, Experimental - chemically induced; Liver Neoplasms, Experimental - metabolism; malachite green; Male; males; NAD(P)H oxidase (H2O2-forming); NADP (coenzyme); NADPH oxidase; NADPH Oxidases - biosynthesis; Precancerous Conditions - metabolism; Precancerous Conditions - pathology; Preneoplastic liver cell lesions; Quercetin - analogs & derivatives; Quercetin - pharmacology; Rats; Rats, Inbred F344; Two-stage hepatocarcinogenesis model; NADPH oxidase; Apocynin; Enzymatically modified isoquercetin; Preneoplastic liver cell lesions; Two-stage hepatocarcinogenesis model; High fat diet
• ISSN: 0940-2993; 1618-1433; 1618-1433
• DOI: 10.1016/j.etp.2016.10.003

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.