Serum ceruloplasmin

In mammals, phenobarbital and phenytoin increase serum ceruloplasmin concentrations (Aaseth and Norseth 1986). Chronic copper poisoning in sheep is exacerbated when diets contain heliotrope plants (Heliotropium sp., Echium spp., Senecio sp.). Aggravated effects of the heliotrope plants include reduced survival and a twofold to threefold increase in liver and kidney copper concentrations when compared to control animals fed copper without heliotropes (Howell et al. 1991). Rats given acutely toxic doses of 2,3,7,8-tetrachlorodibenzo-para-dioxin had elevated concentrations of copper in liver and kidney because of impaired biliary excretion of copper (Elsenhans et al. 1991). Morphine increases copper concentrations in the central nervous system of rats, and dithiocarbam-ates inhibit biliary excretion (Aaseth and Norseth 1986). In human patients, urinary excretion of copper is increased after treatment with D-penicillamine, calcium disodium EDTA, or calcium trisodium diethylenetriamine penta acetic acid (Flora 1991). 

Treated rats had 1000 mg/kg FW liver (vs. 4.7 in controls) lowered hemoglobin, hematocrit, and red cell counts mean survival time of 67 days hepatic and renal histopathology Dose-time-dependent increase in copper concentrations in liver, spleen, and lung little accumulation in muscle and skin. Reduced growth at 2.5 and 3.75 mg/kg BW daily reduced survival at 3.75 mg/kg BW. Maximum copper concentrations recorded, in mg/kg FW (vs. saline controls,) were 710 in liver (<5), 212 in kidney (<10), 7 in lung (<1.5), 27 in spleen (<2.0) 6 in bone (<2.0) and 2.2 in testes (<1.6) Increased serum ceruloplasmin and white blood cell number... 

Masaoka, T., F. Akahori, S. Arai, and K. Sakaguchi. 1987. Effect of paraquat on plasma fibronectin, serum free hydroxyproline, serum ceruloplasmin and lung collagen content in monkeys. J. Toxicol. Sci. 12 329-340. 

Increase in blood and urine Mo levels, increases in serum ceruloplasmin, increased xanthine oxidase activity (11) Increased uric acid, decreased copper excretion, high incidence of gout-like disease (11)... 

Dogan, P., Soyuer, U., Tanrikulu, G. (1989). Superoxide dismutase and myeloperoxidase activity in polymorphonuclear leukocytes, and serum ceruloplasmin and copper levels, in psoriasis. Brit. J. Dermatol. 120,239-44. 

Workers at a molybdenum-roasting plant with time-weighted average (TWA) exposures of approximately 9.5mgMo/m to soluble dusts had increased plasma and urine levels of molybdenum the only adverse biochemical findings were large elevations in serum ceruloplasmin levels and some increase in serum uric acid levels. ... 

A word of comment on the high Cu64 content of the bile seems justifiable, since the exact chemical form of copper excreted in the bile has not been determined. The possibility that ceruloplasmin or some copper-containing metabolite of ceruloplasmin is normally excreted in the bile has not been carefully examined. The abnormal elevation of the serum ceruloplasmin level in acute biliary obstruction (7), and the abnormally low serum ceruloplasmin seen in some cases of advanced liver disease, particularly Wilson s disease (2, 3), are in keeping with the liver being the site of ceruloplasmin synthesis and excretion. 

Wilson s disease is a copper storage disorder that is apparently due to an inherited lesion in the copper excretion mechanism. One in 200-400 persons is a carrier of the disease. Diagnosis may be made by measuring serum ceruloplasmin levels. Whereas normal serum ceruloplasmin is 200-400 mg/L, in Wilson s disease patients it is well below 200 mg/L. Liver copper in these patients (determined by biopsy) is more than 250 /xg/g, whereas normal individuals show a value of only 20-45 /xg/g. Liver function deterioration is the most prominent symptom of Wilson s disease. Treatment includes chelation therapy with penicillamine. 

Wilson s disease Autosommal recessive, low serum ceruloplasmin and increased hepatic copper content. 

Cauza, E., Maier-Dobersberger, T., Polli, C., Kaserer, K., Kramer, L., Ferenci, R Screening for Wilson s disease in patients with liver diseases by serum ceruloplasmin. J. Hepatol. 1997 27 358-362... 

A 17-year-old man with anaemia, leukopenia, and neutropenia had been self-medicating with over-the-counter zinc formulations for acne for almost 2 years at doses of up to 300 mg/day (10). Serum copper and serum ceruloplasmin concentrations were less than 100 (reference range 70-155) ng/ml and 20 (23-49) pg/ml respectively. His serum zinc concentration was 2 (0.6-1.3) pg/ml. Within 1 month of withdrawal, and without copper supplementation, the ceruloplasmin concentration had risen to 90 pg/ml. By 2 months his complete blood count was normal. 

Table III Serum Ceruloplasmin Concentrations in Normal Male Subjects as Reported by Various Authors...

This chapter describes our work on serum-, copper-, and ceruloplasmin-level correlates and aging in a relatively large population. Additionally, we sought to determine if any difference exists between males and females. Since serum ceruloplasmin is closely related to copper and is known to fluctuate under various pathophysiological conditions, it also was decided to analyze the same samples for ceruloplasmin. 

Results. As depicted in Table V, the mean ages, serum copper and serum ceruloplasmin concentrations db standard deviation from 180 male and 44 female subjects were shown. As can be seen, there is no significant difference in serum copper between males and females. However, serum ceruloplasmin in the females was significantly higher than that in the males, with p < 0.01. This seems to agree with most of the reports mentioned earlier (Table IV). It must be pointed out that the mean age... 

Table V. Mean Age, Serum Copper, and Serum Ceruloplasmin Concentrations in Male and Female Subjects"...

Table VI depicts correlation coeflBcient, regression equations, and levels of significance for copper vs. age, ceruloplasmin vs. age, and ceruloplasmin vs. copper. As indicated by the level of significance, there was a high correlation between ceruloplasmin and copper in both males and females (p < 0.005). This was not surprising in view of the fact that 95% of copper in the serum is in the form of ceruloplasmin. When copper concentration was correlated with age, a significant positive correlation was obtained in the males. No such correlation was observed in the females. However, when tests of homogeneity for the regression slopes comparing males and females were applied, no significant differences were noted when comparing serum copper with age or serum ceruloplasmin with age.

Figures 3 and 4 illustrate the relationship between serum ceruloplasmin and age in both males and females, respectively. A significant correlation appears to exist in the male population whereas in the females such a correlation is lacking, but when correlation for males and females are combined, serum ceruloplasmin levels in females were significantly higher than those in males.

Figure 5 depicts correlations between serum ceruloplasmin and copper concentration as can be seen, it is significant in both males and females with p < 0.005, the correlation coeflBcients being 0.36 and 0.84, respectively. However, when different lots of immunodiffusion plates were used and correlation coeflBcients for the samples welre calculated separately, the range of correlation in five lots was 0.30-0.88, with a mean value of 0.53. 

The altered copper metabolism in the aged is not explained by our data since it did not assess copper concentrations in other body pools rich in copper, but the fact that it did increase with age in males while serum ceruloplasmin failed to do so suggests that the level of free ionic copper or copper bound to a small polypeptide molecule is higher in these subjects than the level normally found in serum. Few studies have been reported on tissue copper concentration and its relation to age except for Schroeders work (15), alluded to earlier. He found that copper levels in liver and aorta are significantly decreased after the age of 60, whereas copper concentrations in the brain, kidney, spleen, and heart remain imchanged. 

Figure 3. Serum ceruloplasmin concentrations in 180 males vs. age. The results from each of the five lots of immunodiffusion plates used are shown by different symbols.

Copper Excretion and Serum Ceruloplasmin in Liver Disease, Scand. J. Gastroenterol. (1977) 12 81-SS. 

Cox, D. W., Factors Influencing Serum Ceruloplasmin Levels in Normal... 

Many epileptics receiving anticonvulsants excrete increased amounts of copper and zinc in their urine. Increased serum ceruloplasmin also increases the total serum copper concentration. In 20% to 30% of epileptic children receiving anticonvulsant therapy, erythrocyte aspartate aminotransferase activity is low, indicating a lowered pyridoxal (vitamin Bg) status. In as many as 50% of the adults receiving phenytoin for some time, there will be folate deficiency, manifested by reduced erythrocyte and serum folate concentrations. The mechanism for the deficiency has not yet been established conclusively. In about 10% of adults taking phenytoin, the serum vitamin is low. 

Wilson s disease or ceruloplasmin deficiency (autosomal recessive) Excess secretion of glycine, serine, and cystine Lenticular degeneration, positive copper balance, low serum ceruloplasmin levels, and defects in renal tubular reabsorption Mental retardation, ataxia, extrapyramidal symptoms, and cirrhosis Chromatography low blood and high urine copper levels low serum cemlc Iasmin (B8. H18. H19, PU. S9, W16)... 

Wilson s disease is an autosomal recessive disease of copper metabolism. It has a prevalence of 1 in 30,000 live births in most populations. The disease has a highly variable clinical presentation. It is characterized by impairment of biliary copper excretion, decreased incorporation of copper into ceruloplasmin, and accumulation of copper in the liver and, eventually, in the brain and other tissues. The biochemical findings include low serum ceruloplasmin, high urinary copper excretion, and high hepatic copper content. Some patients have normal serum cerulo-plasmia levels, and heterozygous individuals do not consistently show reduced levels of this protein. 

The defect in copper metabolism is generalized, and the degenerative changes cannot be reversed by parenteral copper administration. However, parenteral copper administration corrects the serum ceruloplasmin and hepatic copper deficiencies. Other tissues take up copper administered parenterally, but activities of their copper enzymes are not normalized. The failure of postnatal treatment is due to the fact that many of the deleterious effects occur in utero. 

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