title: Antimutagenic Effects of Selenium-Enriched Polysaccharides from Pyracantha fortuneana through Suppression of Cytochrome P450 1A Subfamily in the Mouse Liver.
abstract: Both selenium (Se) and polysaccharides fromPyracantha fortuneana(Maxim.) Li (PFPs) (P. fortuneana) have been reported to possess antioxidative and immuno-protective activities. Whether or not Se-containing polysaccharides (Se-PFPs) have synergistic effect of Se and polysaccharides on enhancing the antioxidant and immune activities remains to be determined. We previously reported that polysaccharides isolated from Se-enrichedP. fortuneana(Se-PFPs) possessed hepatoprotective effects. However, it is not clear whether or not they have anti-mutagenic effects. In the present study, we compared and evaluated anti-mutagenic effects of Se-PFPs at three concentrations (1.35, 2.7 and 5.4 g/kg body weight) with those of PFPs, Se alone or Se + PFPs in mice using micronucleus assay in bone marrow and peripheral blood as well as mitomycin C-induced chromosomal aberrations in mouse testicular cells. We also elucidated the underlying mechanism. Our results demonstrated that Se-PFPs inhibited cyclophosphamide (CP)-induced micronucleus formation in both bone marrow and peripheral blood, enhanced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in mouse liver, and reduced the activity and expression of cytochrome P450 1A (CYP4501A) in mouse liver in a dose-dependent manner. In addition, we found that the anti-mutagenic potential of Se-PFPs was higher than those of PFPs, Se alone or Se + PFPs at the same level. These results suggest that the anti-mutagenic potential of Se-PFPs may be mediated through the inhibition of the activity and expression of CYP4501A. This study indicates that application of Se-PFPs may provide an alternative strategy for cancer therapy by targeting CYP1A family.
authors.affiliation: Department of Biochemistry, College of Medical Science, China Three Gorges University, Yichang 443002, China. Fanpeng@ctgu.edu.cn.
authors.forename: Fan
authors.initials: F
authors.lastname: Peng
authors.affiliation: Department of Biochemistry, College of Medical Science, China Three Gorges University, Yichang 443002, China. guoxin951106@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Biochemistry, College of Medical Science, China Three Gorges University, Yichang 443002, China. yuancf46@163.com.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Changzli@163.com.
authors.forename: Changzheng
authors.initials: C
authors.lastname: Li
authors.affiliation: Molecular Medicine & Cancer Research Center, Chongqing Medical University, Chongqing 400016, China. cdwang@cqmu.edu.cn.
authors.forename: Changdong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. weirl@163.com.
authors.forename: Weiran
authors.initials: W
authors.lastname: Lv
authors.affiliation: Renhe Hospital, China Three Gorges University, Yichang 443002, China. Wangjunjiesx@163.com.
authors.forename: Junjie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, College of Medical Science, China Three Gorges University, Yichang 443002, China. fangxx@ctgu.edu.cn.
authors.forename: Fangxiang
authors.initials: F
authors.lastname: Xiao
authors.affiliation: King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia. M.A.kamal@gmail.com.|Enzymoics, 7 Peterlee Place, Hebersham, NSW 2770, Australia. M.A.kamal@gmail.com.
authors.forename: Mohammad Amjad
authors.initials: MA
authors.lastname: Kamal
authors.affiliation: Department of Biochemistry, College of Medical Science, China Three Gorges University, Yichang 443002, China. yuancf46@ctgu.edu.cn.
authors.forename: Chengfu
authors.initials: C
authors.lastname: Yuan
mesh_terms: D000818:Animals; D016587:Antimutagenic Agents / Q000737:chemistry*; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D002869:Chromosome Aberrations; D000072461:Cytochrome P450 Family 1 / Q000037:antagonists & inhibitors*; D004912:Erythrocytes / Q000187:drug effects / Q000473:pathology; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D011134:Polysaccharides / Q000008:administration & dosage / Q000737:chemistry*; D031991:Pyracantha / Q000737:chemistry*; D018036:Selenium Compounds / Q000008:administration & dosage / Q000737:chemistry*; D013482:Superoxide Dismutase / Q000378:metabolism; D013737:Testis / Q000187:drug effects / Q000473:pathology
chemical_list: D016587:Antimutagenic Agents; D011134:Polysaccharides; D018036:Selenium Compounds; D005979:Glutathione Peroxidase; D000072461:Cytochrome P450 Family 1; D013482:Superoxide Dismutase
keywords: CYP1A; Se-PFPs; anti-mutagenicity; micronucleus formation