title: Functional link between ferroxidase activity of ceruloplasmin and protective effect of apo-lactoferrin: studying rats kept on a silver chloride diet.
abstract: Strongly pronounced argyrosis caused by adding AgCl to the feed of laboratory rats efficiently mimics the deficiency of ceruloplasmin (CP) ferroxidase activity. Bringing the concentration of AgCl in the feedstuff of lactating rats to 250 mg % and keeping their progeny (Ag-rats) for 3 months on the same silver-containing feed provided the serum iron content 1.4 times lower than that in the control group. Besides, the ferroxidase activity of CP dropped to zero. In CP purified from sera of Ag-rats two copper ions were substituted with two silver ions. Using rat models of both post-hemorrhagic and hemolytic anemia we showed that the deficiency of CP ferroxidase activity in Ag-rats affects the iron content in serum, though does not prevent the recovery of hemoglobin level accompanied by exhaustion of iron caches in liver and spleen. When apo-lactoferrin (apo-LF) was administered to Ag-rats suffering from either post-hemorrhagic or hemolytic anemia, both hemoglobin and serum iron were restored more rapidly than in the control animals. In independent experiments Ag-rats were compared with those fed on regular diet and the former displayed a prolonged 3-day stabilization of hypoxia-inducible factors 1 and 2 alpha (HIF-1a and HIF-2a) along with an increased serum concentration of erythropoietin. Introduction to Ag-rats of active CP separately or together with apo-LF reduced that effect to 1 day only. It is concluded that saturation of apo-LF with iron, provided by active CP, can strongly affect its protective capacity.
authors.affiliation: Institute for Experimental Medicine, Pavlov street 12, Saint Petersburg, 197376, Russia.
authors.forename: Valeria A
authors.initials: VA
authors.lastname: Kostevich
authors.affiliation: Institute for Experimental Medicine, Pavlov street 12, Saint Petersburg, 197376, Russia. biochemsokolov@gmail.com.|Saint-Petersburg State University, Mendeleevskaya line, Saint Petersburg, 199000, Russia. biochemsokolov@gmail.com.
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Sokolov
authors.affiliation: Institute for Experimental Medicine, Pavlov street 12, Saint Petersburg, 197376, Russia.
authors.forename: Stanislav O
authors.initials: SO
authors.lastname: Kozlov
authors.affiliation: Institute for Experimental Medicine, Pavlov street 12, Saint Petersburg, 197376, Russia.
authors.forename: Anna Yu
authors.initials: AY
authors.lastname: Vlasenko
authors.affiliation: Institute for Experimental Medicine, Pavlov street 12, Saint Petersburg, 197376, Russia.
authors.forename: Nikolay N
authors.initials: NN
authors.lastname: Kolmakov
authors.affiliation: Institute for Experimental Medicine, Pavlov street 12, Saint Petersburg, 197376, Russia.
authors.forename: Elena T
authors.initials: ET
authors.lastname: Zakharova
authors.affiliation: Institute for Experimental Medicine, Pavlov street 12, Saint Petersburg, 197376, Russia.|Saint-Petersburg State University, Mendeleevskaya line, Saint Petersburg, 199000, Russia.
authors.forename: Vadim B
authors.initials: VB
authors.lastname: Vasilyev
mesh_terms: D000208:Acute Disease; D000740:Anemia / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D002570:Ceruloplasmin / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000378:metabolism*; D004032:Diet; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000188:drug therapy*; D007501:Iron / Q000378:metabolism; D007781:Lactoferrin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018030:Silver Compounds / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D018030:Silver Compounds; D007501:Iron; D002570:Ceruloplasmin; D007781:Lactoferrin; C037548:silver chloride
keywords: Ceruloplasmin; Erythropoietin; Ferroxidase; Hemolytic anemia; Hypoxia-inducible factor; Iron metabolism; Lactoferrin; Post-hemorrhagic anemia; Transferrin