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Abstract <p>Ceruloplasmin (Cp) plays a key role in the metabolism of twovital trace elements, iron and copper, whose metabolic pathwaysare closely interconnected and also linked to zinc metabolism. Tumorgrowth is often accompanied by an increase in blood Cp concentration,but its role in tumor progression remains unclear. The aim of thisstudy was to compare changes in serum Cp concentration with thelevels of iron, zinc, pro-inflammatory cytokines, and lipids duringtumor growth. Additionally, we investigated the effect of zinc sulfate,administered in drinking water, on Cp levels. The study was carriedout on C3HA mice subcutaneously inoculated with hepatoma 22a cells.An increase in Cp began on day 14, coinciding with the emergenceof central necroses and elevated circulating triglyceride levels.The rise in blood IL-6 concentration started on day 7 and couldserve as a trigger for the acute-phase response development, as manifestedby increased Cp synthesis, hypoferremia, hypozincemia, and hypertriglyceridemia.The decrease in non-heme iron levels in the blood and liver occurredlater than the Cp increase, suggesting that iron deficiency wasnot the cause of the elevated Cp concentration on day 14 but mightcontribute to its maintenance at later stages of hepatoma growth.Zinc sulfate supplementation normalized iron and partially restoredzinc levels in the blood of tumor-bearing mice by day 21 but didnot affect Cp concentration. The potential pro-tumorigenic roleof Cp is discussed, which may be not so much related to its rolein iron metabolism as to its ability to transport copper to tissuesWe hypothesize that serum Cp is an important pathogenetic factorin supplying tumors with essential lipid metabolites, as Cp, together withIL-6, may support lipolysis in adipose tissue by delivering copperions.</p>

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Metabolic Disorders in Mice Bearing Transplantable Hepatoma 22a: a Focus on Ceruloplasmin

  • 期刊论文

  • 发表日期：

    2025年5月1日

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  • E. A. Zelenskyi,
  • K. V. Rutto,
  • A. S. Trulioff,
  • N. P. Gorbunov,
  • A. V. Sokolov,
  • E. P. Kisseleva

摘要

Abstract

Ceruloplasmin (Cp) plays a key role in the metabolism of twovital trace elements, iron and copper, whose metabolic pathwaysare closely interconnected and also linked to zinc metabolism. Tumorgrowth is often accompanied by an increase in blood Cp concentration,but its role in tumor progression remains unclear. The aim of thisstudy was to compare changes in serum Cp concentration with thelevels of iron, zinc, pro-inflammatory cytokines, and lipids duringtumor growth. Additionally, we investigated the effect of zinc sulfate,administered in drinking water, on Cp levels. The study was carriedout on C3HA mice subcutaneously inoculated with hepatoma 22a cells.An increase in Cp began on day 14, coinciding with the emergenceof central necroses and elevated circulating triglyceride levels.The rise in blood IL-6 concentration started on day 7 and couldserve as a trigger for the acute-phase response development, as manifestedby increased Cp synthesis, hypoferremia, hypozincemia, and hypertriglyceridemia.The decrease in non-heme iron levels in the blood and liver occurredlater than the Cp increase, suggesting that iron deficiency wasnot the cause of the elevated Cp concentration on day 14 but mightcontribute to its maintenance at later stages of hepatoma growth.Zinc sulfate supplementation normalized iron and partially restoredzinc levels in the blood of tumor-bearing mice by day 21 but didnot affect Cp concentration. The potential pro-tumorigenic roleof Cp is discussed, which may be not so much related to its rolein iron metabolism as to its ability to transport copper to tissuesWe hypothesize that serum Cp is an important pathogenetic factorin supplying tumors with essential lipid metabolites, as Cp, together withIL-6, may support lipolysis in adipose tissue by delivering copperions.