RESUMEN
Mannans, which are biological macromolecules of polysaccharide origin and function as immunomodulators, have been shown to stimulate macrophages in vivo by interaction with the mannose receptor. Thus, they can be used to stimulate macrophages in order to effectively remove circulating atherogenic lipoproteins. Our primary aim was to evaluate the hypolipidemic potential of mannans from C. albicans serotype A (mannan A) and serotype B (mannan B) in a murine model of hyperlipidemia. Mannan A and mannan B were shown to significantly (p<0.05) stimulate both the proliferation (p <0.05) and nitric oxide production of murine peritoneal macrophages in vitro. Pre-treatment of CBA/Lac mice with mannan A prior to induction of hyperlipidemia significantly (p<0.001) reduced serum atherogenic LDL-cholesterol, total cholesterol, and triglycerides. Mannan B exhibited a similar, but more potent, hypolipidemic effect. Electron microscopic analysis of liver revealed a significant (p<0.001) decrease in the volume of lipid droplets when hyperlipidemic mice were pretreated by both mannans. In conclusion, our findings would suggest that both polysaccharide-based biological macromolecules evaluated in the present study, specifically, the natural immunomodulators (mannans A and B), appeared to function as effective lipid-lowering macromolecules, which could potentially serve as adjunct therapy to more conventional hypolipidemic medications such as a statin drug.
Asunto(s)
Hiperlipidemias/tratamiento farmacológico , Hipolipemiantes/química , Mananos/química , Polisacáridos/química , Animales , Candida albicans/química , Proliferación Celular/efectos de los fármacos , Humanos , Hiperlipidemias/metabolismo , Hiperlipidemias/patología , Hipolipemiantes/administración & dosificación , Hipolipemiantes/aislamiento & purificación , Gotas Lipídicas/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Mananos/administración & dosificación , Mananos/aislamiento & purificación , Ratones , Óxido Nítrico/biosíntesis , Polisacáridos/administración & dosificación , Polisacáridos/aislamiento & purificación , Serogrupo , Triglicéridos/metabolismoRESUMEN
The study examined dynamics of the effect of novel phenol antioxidant preparation 3-(3'-tertbutyl- 4'-hydroxyphenyl)propyl thiosulfonate sodium (TS-13) on expression of antioxidant protection enzymes genes GSTP1 and NQO1 and on the content of protein transcription factors NF-κB and ATF-2 in mouse liver. Expression of GSTP1 gene decreased significantly on days 4 and 7 after per os administration of TS-13 (100 mg/kg), but increased on post-administration day 14. On days 7 and 14 post-administration, expression of NQO1 gene was significantly increased. On day 7, the hepatic content of the phosphorylated form of ATF-2 and two subunits of nuclear factor NF-κB (p50, p65) decreased significantly.
Asunto(s)
Factor de Transcripción Activador 2/genética , Antioxidantes/farmacología , Gutatión-S-Transferasa pi/genética , NAD(P)H Deshidrogenasa (Quinona)/genética , FN-kappa B/genética , Ácidos Tiosulfónicos/farmacología , Factor de Transcripción Activador 2/metabolismo , Administración Oral , Animales , Expresión Génica/efectos de los fármacos , Gutatión-S-Transferasa pi/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , FN-kappa B/metabolismo , Fosforilación , Factores de TiempoRESUMEN
Activity and levels of protein and mRNA of 3-hydroxy-3-methyl-glutaryl-CoA reductase were estimated in rat liver after the administration of atorvastatin and simvastatin and their complexes with glycyrrhizic acid (atorvaglyzin and simvaglyzin). The amount of 3-hydroxy-3-methyl-glutaryl-CoA reductase protein in rats decreased by 13 and 25% (p<0.05) 24 h after treatment with atorvaglyzin and simvaglyzin, respectively. Activity of this enzyme decreased by 46% in rats treated with atorvaglyzin. The amount of messenger RNA in these groups significantly increased as compared to control group (untreated animals).
