Isotopic analysis of Cu in blood serum by multi-collector ICP-mass spectrometry: a new approach for the diagnosis and prognosis of liver cirrhosis?

Abstract

The isotopic composition of blood serum Cu has been investigated as a potential parameter for the diagnosis and prognosis of liver cirrhosis. Serum samples from supposedly healthy women (reference population) and from a group of female patients suffering from liver cirrhosis of different etiologies were analysed. The procedure for isolation of serum Cu and the measurement protocol for its isotopic analysis by multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS) were evaluated. Significant differences in the isotopic composition of Cu were observed between the reference population and the patients. A wide spread in δ(65)Cu was observed within the cirrhosis population and δ(65)Cu seems to be linked to the severity of the disease. Patients with end-stage liver disease showed a significantly lighter serum Cu isotopic composition. Many clinical parameters used for the diagnosis and monitoring of liver diseases, i.e. the levels of aspartate aminotransferase, De Ritis ratio, prothrombin and international normalized ratio, albumin, bilirubin, Na and C-reactive protein, correlate well with the δ(65)Cu values, as did the ceruloplasmin level and the ceruloplasmin/Cu concentration ratio. The isotopic composition of serum Cu appears to reveal the synthetic and hepatocellular function of the liver synergistically with inflammation and fluid retention in the cohort studied. A relevant relationship was also observed between δ(65)Cu and scores of mortality risk, such as the Model for End-stage Liver Disease (MELD) and MELD-Na. Thus, the isotopic composition of serum Cu shows potential as a new approach for the prognosis of liver disease, and although further investigation is required, for evaluation of the mortality risk in end-stage liver disease and prioritization of liver transplants.

Copper and zinc isotope ratios in human bone and enamel

“…The first studies focusing on copper (Cu) and zinc (Zn) isotopic variations in human tissues were conducted on blood samples (Table ). In blood, δ 65 Cu values vary according to biological sex (Albarède, Telouk, Lamboux, Jaouen, & Balter, ), menopause (Jaouen & Balter, ; Van Heghe, Deltombe, Delanghe, Depypere, & Vanhaecke, ), and metabolic diseases (Aramendía, Rello, Resano, & Vanhaecke, ; Balter et al, ; Costas‐Rodríguez et al, ; Resano et al, ; Télouk et al, ) and possibly diet (Van Heghe, Engström, Rodushkin, Cloquet, & Vanhaecke, ). While the δ 66 Zn values in blood do not differ between men and women (Albarède et al, ; Van Heghe et al, ), the values are impacted by diseases (Larner et al, ; Stenberg et al, ) and diet (Costas‐Rodríguez, Van Heghe, & Vanhaecke, ; Van Heghe et al, ).…”

Evidence of isotopic fractionation of natural uranium in cultured human cells

“…The isotopic fractionation of medium-mass endogen elements (i.e., Ca, Fe, Cu, and Zn) has recently been shown to have an outstanding potential for biomedical applications (1). Isotopic fractionation measurements have been identified as new biomarkers for the investigation of metabolic processes (2-6) and as powerful tools for the early detection of diseases (7)(8)(9)(10)(11)(12). Studies of Cu and Zn isotopic fractionation are very promising for the early diagnosis of different types of cancer (9,12) and neurodegenerative diseases (8,13), whereas Fe and Ca isotopic fractionation measurements have shown their ability to monitor Fe absorption efficiency (3) and bone mineral balance (7), respectively.…”

Copper isotopes as possible neoplasia biomarkers in captive wild felids

“…This copper isotope uptake within the cell can explain the variation in the δ 65 Cu concentration in blood with neoplasia. The third explanation for low δ 65 Cu implies biosynthetic and hepatocellular dysfunction of the liver with inflammation (Costas‐Rodríguez et al, ). In any case, several intrinsic or extrinsic factors can be proposed to explain the development of tumors observed for Group 2.…”