title: In vitro enzyme-mimic activity and in vivo therapeutic potential of HSJ-0017, a novel Mn porphyrin-based antioxidant enzyme mimic.
abstract: Manganese (III) 5, 10, 15, 20-tetrakis [3-(2-(2-methoxy)-ethoxy) ethoxy] phenyl porphyrin chloride, designated HSJ-0017, is a novel antioxidant enzyme mimic. The aim of the present study was to investigate the enzyme-mimic activity and the therapeutic potential of HSJ-0017 in free radical-related diseases. Superoxide dismutase (SOD) mimic activity was measured by the nitroblue tetrazolium chloride monohydrate reduction assay. Catalase (CAT) mimic activity was measured based on the decomposition of hydrogen peroxide. The antitumor, radioprotective and chemoprotective effects of HSJ-0017 were evaluated in H22 or S180 tumor-bearing Kunming mice. The anti-inflammatory and hepatoprotective effects were, respectively, evaluated in histamine-induced edema model and CCl4-induced hepatic damage model in Wistar rats. HSJ-0017 over a concentration range of 0.001-10 µmol/L significantly inhibited the generation of superoxide anion. Significant hydrogen peroxide scavenging activity was observed when the concentration of HSJ-0017 was higher than 0.01 µmol/L. HSJ-0017 at a dose of 3.0 mg/kg exhibited significant antitumor effect on S180 tumor xenografts, whereas no significant antitumor effect was observed in H22 tumor xenografts. HSJ-0017 at a dose of 3.0 mg/kg enhanced the antitumor effects of radiotherapy and chemotherapy, and reduced their toxicity. However, HSJ-0017 counteracted the antitumor effects of radiotherapy when administered simultaneously with radiotherapy. HSJ-0017 showed significant anti-inflammatory and hepatoprotective effects. Our results demonstrate that HSJ-0017 exhibits antioxidant, antitumor, anti-inflammatory, radioprotective, chemoprotective, and hepatoprotective effects. It is a potent dual SOD/CAT mimic.
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Bao-qiu
authors.initials: BQ
authors.lastname: Li
authors.affiliation: Shandong Hongli Laboratory Animal Experiment Co, Ltd, Jinan, Shandong 250101, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Dong
authors.affiliation: Shandong Hongli Laboratory Animal Experiment Co, Ltd, Jinan, Shandong 250101, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Shandong Hongli Laboratory Animal Experiment Co, Ltd, Jinan, Shandong 250101, China.
authors.forename: Ji-you
authors.initials: JY
authors.lastname: Gao
authors.affiliation: Shandong Hongli Laboratory Animal Experiment Co, Ltd, Jinan, Shandong 250101, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Shandong Hongli Laboratory Animal Experiment Co, Ltd, Jinan, Shandong 250101, China.
authors.forename: Shi-hong
authors.initials: SH
authors.lastname: Fang
authors.affiliation: Jinan Saiwen Pharmaceuticals, Inc, Jinan, Shandong 250101, China;
authors.forename: Xian-chang
authors.initials: XC
authors.lastname: Gong
authors.affiliation: Jilin Province A-Think Pharmaceutical Co, Ltd, Changchun, Jilin 130616, China.
authors.forename: Shu-juan
authors.initials: SJ
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong 250012, China wangfengshanda@126.com.
authors.forename: Feng-shan
authors.initials: FS
authors.lastname: Wang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000378:metabolism* / Q000627:therapeutic use*; D032701:Biomimetics; D016166:Free Radical Scavengers / Q000378:metabolism* / Q000627:therapeutic use*; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D008665:Metalloporphyrins / Q000378:metabolism* / Q000627:therapeutic use*; D051379:Mice; D009580:Nitroblue Tetrazolium / Q000378:metabolism; D010084:Oxidation-Reduction; D017208:Rats, Wistar; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D000975:Antioxidants; D016166:Free Radical Scavengers; D005765:Gastrointestinal Agents; D008665:Metalloporphyrins; C586813:manganese (III) meso-tetra (3-(2-(2-methoxy)-ethoxy) ethoxy)phenyl porphyrin chloride; D009580:Nitroblue Tetrazolium; D006861:Hydrogen Peroxide
keywords: Mn-porphyrins; antioxidant; free radical; radioprotection; superoxide dismutase