Marginal Copper Deficiency Increases Liver Neutrophil Accumulation After Ischemia/Reperfusion in Rats

Abstract

Copper deficiency can cause a host of major cardiovascular complications including an augmented inflammatory response through effects on both neutrophils and the microvascular endothelium. In the present study, we evaluated the effect of marginal copper deficiency on the neutrophilic response to hepatic ischemia/reperfusion injury, a condition that induces an inflammatory response. Male weanling Sprague–Dawley rats were fed purified diets which were either copper-adequate (6.3 mg/kg) or copper-marginal (1.62 mg/kg) for 4 weeks prior to undergoing 90 min of partial hepatic ischemia followed by 8 h of reperfusion. Liver injury was assessed by serum levels of alanine aminotransferase and by liver histology. Liver neutrophil accumulation was determined by tissue myeloperoxidase content. There was no significant difference in liver injury between copper-adequate and copper-marginal rats. However, liver neutrophil accumulation was significantly increased in copper-marginal rats. These findings were confirmed histologically. Liver expression of the adhesion molecule, intercellular adhesion molecule-1 (ICAM-1), was increased in copper-marginal rats compared to copper-adequate rats. The results suggest that neutrophil accumulation is increased through enhanced ICAM-1 expression in liver of copper-marginal rats after ischemia/reperfusion, but that this does not result in increased liver injury.

The Coppery Age: Copper (Cu)‐Involved Nanotheranostics

“…[47] Especially, copper deficiency can induce a series of diseases including cardiovascular disease and diabetes. [246][247][248][249] However, the high Cu accumulation might induce the potential toxicity issue in the body, despite some Cu-based nanoagents have been preliminarily demonstrated to be biocompatible. Therefore, the in vivo biological effect and biosafety of the developed Cu-involved nanosystems should be carefully and systematically assessed for guaranteeing their further clinical translation.…”

Protective effect of Xuebijing injection against acute lung injury induced by left ventricular ischemia/reperfusion in rabbits

“…Under normal circumstances, the protein expression levels of ICAM-1 are negligible, and this prevents pathological damage to the body ( 29 ). However, during I/R and other pathological conditions, the expression of proinflammatory mediators is stimulated and the expression levels of ICAM-1 are increased significantly ( 30 ). This in turn promotes the adherence of neutrophils to endothelial cells and their migration across the endothelial barrier, resulting in inflammation and various pathological changes that characterize reperfusion injury ( 7 ).…”

Copper homeostasis and cuproptosis in atherosclerosis: metabolism, mechanisms and potential therapeutic strategies

“…Evidence from animal studies also supports the role of copper deficiency in inflammation. For example, neutrophil accumulation increases due to increased ICAM-1 expression in the livers of copper-deficient rats following ischemia/reperfusion [ 79 ]. Further, this elevated ICAM-1 expression has been shown to activate neutrophils and endothelial cells, as evidenced by F-actin polymerization and increased accumulation of neutrophils within the lung microcirculation [ 80 – 82 ].…”