Ceruloplasmin Oxidase Activity Research Articles

Serum ceruloplasmin oxidase activity: A neglected diagnostic biomarker for Wilson disease

BackgroundLow serum ceruloplasmin concentration is considered robust marker for Wilson disease (WD) screening, measuring serum ceruloplasmin oxidase activity might be an even more valuable diagnostic tool, but it has not been sufficiently studied. MethodsAll patients who were assessed for serum ceruloplasmin oxidase activity between January 1, 2016, and September 2, 2019, were enrolled in this study. The diagnostic performance of serum ceruloplasmin oxidase activity was analyzed using receiver operating characteristic curve analysis (ROC), Spearman's rank correlation, and Mann-Whitney U test. ResultsSerum ceruloplasmin oxidase activity was significantly decreased in WD patients (0.87 U/L, IQR 0.61–1.54). The optimal cut-off of serum ceruloplasmin oxidase activity to identified WD is 7 U/L, with sensitivity and specificity of 97.03 % and 98.19 %, respectively. Furthermore, this study revealed a positive correlation between enzymatic and immunoreactive serum ceruloplasmin tests. As primary diagnostic methods, serum ceruloplasmin levels below the diagnostic cut-offs for either the enzymatic or immunoreactive tests were observed in 818 out of 842 WD patients (97.15 %). Compared with the presence of K-F rings in asymptomatic patients, the accuracy of serum ceruloplasmin tests was significantly higher (56.12 % VS 95.08 %). Moreover, the positive rate of cranial MRI in neurological patients was similar to the tests of serum ceruloplasmin (92.91 % VS 97.40 %). Moreover, 71 patients had ambiguous genetic results, complicating the diagnosis. However, serum ceruloplasmin tests successfully identified 65 out of these 71 patients (91.55 %). ConclusionSerum ceruloplasmin oxidase activity has excellent performance in diagnosing WD, which should be widely used as preferred test in WD patients.

Determination of copper status by five biomarkers in serum of healthy women

BackgroundThe essential trace element copper is relevant for many important physiological processes. Changes in copper homeostasis can result from disease and affect human health. A reliable assessment of copper status by suitable biomarkers may enable fast detection of subtle changes in copper metabolism. To this end, additional biomarkers besides serum copper and ceruloplasmin (CP) concentrations are required. ObjectivesThe aim of this study was to investigate the emerging copper biomarkers CP oxidase (CPO) activity, exchangeable copper (CuEXC) and labile copper in serum of healthy women and compare them with the conventional biomarkers total serum copper and CP. Method and main findingsThis observational study determined CPO activity, the non CP-bound copper species CuEXC and labile copper, total serum copper and CP in sera of 110 healthy women. Samples were collected at four time points over a period of 24 weeks. The concentrations of total serum copper and CP were within the reference ranges. The comparison of all five biomarkers provided insight into their relationship, the intra- and inter-individual variability as well as the age dependence. The correlation and Principal Component Analyses (PCA) indicated that CP, CPO activity and total copper correlated well, followed by CuEXC, while the labile copper pool was unrelated to the other parameters. ConclusionsThis study suggests that the non-CP-bound copper species represent copper pools that are differently regulated from total copper or CP-bound copper, making them interesting complementary biomarkers to enable a more complete assessment of body copper status with potential relevance for clinical application.

Effect of dendritic cell vaccine on blood redox status in patients with cervical cancer

Purpose of the study. The purpose of the study was to evaluate the dynamics of parameters of malondialdehyde (MDA), reduced glutathione and antioxidant enzyme activity in patients with advanced cervical cancer (CC) receiving anticancer treatment with dendritic cell vaccine (DCV).Patients and methods. Levels of malondialdehyde (MDA), reduced glutathione and antioxidant enzyme activity were studied in 27 patients aged 27–65 years with advanced primary and recurrent CC receiving chemotherapy (CT) with DCV or DCV as monotherapy at a dose of 10 million cells intradermally once a week. The same indices were studied in 20 healthy women from the comparison group.Results. The majority of patients showed the initial increase of MDA: in blood plasma by an average of 66.7 %, in red blood cells – statistically insignificant. After CT, MDA levels were elevated respectively in primary and recurrent patients in erythrocytes by 85.6 % and 96.4 % compared to donors, and by 53.9 % and 33.7 % compared to the initial values; the levels in plasma were elevated by 79.8 % and 57.1 % compared to donors. After 5–7 DCVs in combination with CT, MDA levels in erythrocytes and in blood plasma were similar to the donor values. MDA in erythrocytes of patients receiving DCV without CT decreased by 36 % compared to initial values. Oxidase activity of ceruloplasmin, initially increased by 34.2–57.1 %, normalized after DCV. Superoxide dismutase activity decreased by 16.7–27.3 % after 4–6 DCVs and normalized after 7 DCVs. Catalase activity, initially reduced by more than 40 %, remained 20–38 % lower than the norm at all stages of DCV. In this setting, hydrogen peroxide was probably inactivated by glutathione peroxidase whose activity was increased at all stages of treatment and decreased only when MDA was normalized after 7 DCVs.Conclusion. Administration of 5–7 DCVs in combination with CT or as monotherapy to patients with advanced CC normalizes parameters of free radical oxidation and antioxidant system of the blood.

Ceruloplasmin Interferes with the Assessment of Blood Lipid Hydroperoxide Content in Small Ruminants.

Simple and inexpensive analytical methods for assessing redox balance in biological matrixes are widely used in animal and human diagnostics. Two of them, reactive oxygen metabolites (ROMs) and total oxidant status (TOS), evaluate the lipid hydroperoxide (LOOH) content of the sample and are based on iron-mediated mechanisms. However, these tests provide uncorrelated results. In this study, we compared these two tests in the blood serum of goat kids and lambs, together with an evaluation of ceruloplasmin (CP) oxidase activity. No significant correlation was found between ROMs and TOS, or between TOS and CP oxidase activity, in either species. Conversely, ROMs and CP oxidase activity were highly correlated in both kid and lamb samples (p < 0.001). A significant progressive reduction in the analytical signal in the ROMs assay was observed when sodium azide, an effective CP inhibitor, was added to the samples before the assay (p < 0.001). This decrease was related to sodium azide concentration (p < 0.01) and was not found when sodium azide was added at the same concentrations in the TOS assay. These findings suggest that ROMs, unlike TOS, may be affected by CP, which interferes with LOOH detection in blood samples.

Relation between redox potential and natural antibody levels in goat kid serum

The redox potential and the natural antibody (NAb) levels are parameters commonly tested to verify the physiological response to stressful situations determined by farming conditions or research needs. In this paper, the redox potential, assessed by different spectrophotometric methods, was related to NAb levels together with total immunoglobulin (tot-Ig) levels in goat kid serum. Reactive oxygen metabolites (ROMs) and ceruloplasmin (CP) oxidase activity were significantly associated with NAb-IgG and NAb-IgM. Nitric oxide metabolites (NOx) and total thiol levels (TTLs) were significantly related to NAb-IgM and tot-IgM, and with NAb-IgG, respectively. A tendency was shown between ROMs and tot-IgM, and between CP and tot-IgM, where, however, the significance levels were above the cut-off values. Total oxidant status (TOS), total antioxidant activity (TAA), determined by the ABTS-based method, the ferric reducing ability of plasma (FRAP), and free radical scavenging activity (FRSA) were associated with neither NAb nor tot-Ig. The obtained results are discussed in light of the possible linkage between the (anti)oxidant status and the innate immune system in goats.

Determination of Ceruloplasmin Oxidase Activity, Copper and Iron in Seminal Fluid of Fertile and Infertile Males

Determination of Ceruloplasmin Oxidase Activity, Copper and Iron in Seminal Fluid of Fertile and Infertile Males

Ceruloplasmin Activity and Ferritin in Patients with Chronic Liver Disease

Background: Ceruloplasmin (CP) is a copper-containing glycoprotein found in the globulin portion of human blood serum 2. CP, a glycoprotein secreted by hepatocytes, carries more than 90% of copper in the bloodstream of healthy people. CP is an effective antioxidant that prevents lipid peroxidation by removing oxygen. CP inhibits lipid peroxidation initiation. CP has function also known as an extracellular superoxide dismutase species (SOD) that neutralizes radicals of superoxide anions. Aims: The aim of this study is to understand the status of CP in chronic liver disease (CLD) patients, which could yield important information regarding the overall oxidative stress and iron storage. Out of the total 86 samples, 50 samples were patients who have been diagnosed with CLD, especially chronic hepatitis B virus (HBV) and hepatitis C virus (HCV), collected from the Center of Internal Medicine and Cardiology in Marjan Teaching Hospital in Hillah city, Babylon Province, Iraq and other samples were healthy controls. Materials and Methods: The CP oxidase activity test was processed by PPD buffer oxidation. Ferritin concentration was tested by enzyme-linked immunosorbent assay. Results: There were no significant differences in levels of ferritin between HBV and HCV patient groups, but there are slight increases in the mean of CP activity in the HCV patients. A positive significant correlation was observed between CP activity and ferritin. Conclusion: 1. CP activity increases in CLD patient and in HCV more than HBV. 2. CP activity is affected by viral load so it increases in positive viral load patients compared with negative viral load patients. 3. There was a positive correlation between CP activity and ferritin. 4. Serum ferritin is not affected by CLD.

Evaluation of Ceruloplasmin Oxidase Activity in Sera of Breast Cancer Individuals in Kurdistan Region/ Iraq

Ceruloplasmin is considered the main copper transport protein which is proposed to have a role in cancer. Ceruloplasmin is an acute phase reactant and antioxidant enzyme, has been found to be increased in sera of patients with several types of cancers including breast cancer.&#x0D; The aim of present study was to determine of ceruloplasmin oxidase activity, specific activity, iron concentration in sera of patients with breast cancer and comparing with healthy group, and the ability of using enzyme as a tumor marker for breast cancer.&#x0D; This study was performed from November 2018 to January 2019, blood samples were collected from breast cancer patients in Nanakeli Hospital in Erbil city. Study was included (65) female patients with breast cancer and (20) healthy donors as control group. Ceruloplasmin activity, specific activity, serum total protein concentration, serum total iron concentration levels were estimated for all samples by colorimetric methods. &#x0D; The results shown that there was a significant increase in ceruloplasmin activity level for patients with breast cancer ( 227.8 U/L) compared with control group (101.1 U/L) while total protein level for breast cancer patients (6.592 g/dl) showed no significant change compared to control group(7.127 g/dL) likewise the result shown that there was a significant increase in specific activity of ceruloplasmin and total iron concentration level for patients with breast cancer (34.74 U/mg) (334.2 mg/dl) compared to control group (14.14 U/mg) (128.6 mg/dl) The conclusion of this study was the concentration of ceruloplasmin activity, serum total iron concentration and specific activity of ceruloplasmin significantly increase in breast cancer patients while total protein level revealed no significant change.&#x0D; Serum ceruloplasmin oxidase activity and specific activity were highly significant elevated in patient group when compared with control group. Also the total iron concentration results showed significant increasing (PË‚0.0001) between of patient with breast cancer and control group.

Assessment of total (anti)oxidant status in goat kids

The redox potential of goat serum was assessed by different spectrophotometric assays. Among them, three methods are commonly applied for the evaluation of the oxidative (reactive oxygen metabolites, ROMs, and total oxidant status, TOS) and nitrosative (NO metabolites, ) stress, and four methods for the evaluation of the antioxidant status: the total antioxidant capacity (TAC) based on the ferric reducing ability of plasma (FRAP), the total antioxidant activity (TAA) based on the reduction of the coloured ABTS radical cation, the free radical scavenging activity (FRSA) based on the reduction of the purple DPPH, and the total thiol levels (TTLs) based on their interaction with DTNB to form a highly coloured anion. Besides, myeloperoxidase (MPO) and ceruloplasmin oxidase (CP) activities were also assessed.Except for TAA, analytical data showed a great inter-individual variation for both oxidant and antioxidant assays. ROMs were strongly correlated with CP, while TOS with MPO and TAC. Furthermore, a tendency between TOS and FRSA was shown. was correlated with TAC and TAA, and a tendency with TOS was shown. No correlations appeared among the antioxidant assays, even if a tendency between TAC and TAA was evidenced, but TAC was correlated with MPO activity. The observed correlation between ROMs and CP is discussed as a possible analytical interference.The absence of correlation among the antioxidant biomarkers suggests the simultaneous use of a panel of tests to verify any changes in the redox balance, mainly in livestock in which reference values for each biomarker are lacking.

Effect of Narrowband-UVB Phototherapy Treatment on Total Ferroxidase Activity and Ceruloplasmin Oxidase Activity in Sera of Iraqi Vitiligo Patients

Vitiligo is an acquired pigmentary disorder in which white depigmented macules and patches of skin appear on different parts of the body, affecting all ages and both sexes equally. Focal, segmen-tal, generalized and universal are considered the most characteristic patterns of vitiligo. One of the most effective treatment of this disorder is using light therapy, and in particular ultraviolet (UV) light. Among them narrowband ultraviolet B phototherapy (NB-UVB) is the most widely used. Oxidative stress is considered to be one of the possible pathogenic events in melanocyte loss. Imbalance in the oxidant/antioxidant system have been demonstrated in blood of vitiligo patients. To demonstrate the safety of using NB-UVB phototherapy treatment in vitiligo Iraqi patients. Patients with vitiligo group were treated with NB-UVB regimen as three times weekly on non- consecutive days for a total of 20 sessions (about 2 months). Total ferroxidase (activity and specific activity), ceruloplasmin concentration, ceruloplasmin oxidase (activity and specific activity) and serum copper were determined in all participants before and after NBUVB phototherapy. The above biochemical parameters were measured in serum samples of 30 vitiligo patients before and after treatment with the narrow band UVB phototherapy. NB-UVB treatment was found to be associated with a significant reduction in copper ion concentration, but no significant differences in total ferroxidase (activity and specific activity), ceruloplasmin oxidase (activity and specific activity), and ceruloplasmin concentration. The present results provide evidence which support using narrow band UVB phototherapy as a safe method for vitiligo treatment.

A low blood copper concentration is a co-morbidity burden factor in Parkinson’s disease development

Parkinson’s disease (PD) patients are often characterized by copper dyshomeostasis, which is responsible for ROS formation and fibrillogenesis. However, the relationships between copper metabolism and PD development are unclear. In this study in 50 patients with PD (pPD) and 50 age-matched healthy individuals, the serum total copper concentration, oxidase activity, ceruloplasmin and SOD3 protein concentrations were measured; and amount of copper atoms per ceruloplasmin molecule was calculated. These parameters were lower in pPD relatively to healthy volunteers. Decrease in concentrations of SOD3, ceruloplasmin, and copper but increase of interleukin-6 levels were associated with a risk of PD. Two consistent patterns were identified. First, a low serum copper concentration related with PD development and predominantly affected the non-motor symptoms of PD. There was no correlation between copper concentration and ceruloplasmin oxidase activity level (r = 0.27) in pPD. Second, Chelex 100 treatment revealed that pPD ceruloplasmin compared with ceruloplasmin of healthy individuals displayed smaller content of labile copper atoms. The presence or absence of these atoms had no effect on ceruloplasmin enzymatic activities. Our findings suggest that cuproenzyme deficiency, which is typical for PD, can be caused by violation of metabolic incorporation of the labile copper atoms into ceruloplasmin molecule.

Some Biochemical Risk Factors for Myocardial Infarction in Babylon City

The present comprehensive study was designed to investigate the changes in some biochemical parameters and determine the risk factors in sera samples of patient with myocardial infarction (MI) [history of diabetes mellitus (DM) type 1, hypertension (blood pressure BP), and DM+ BP+smoking].Sixty four patients with MI attending to Merjan Teaching Hospital in Hilla City, were included in the present study. Also thirty two healthy individuals of matched age and gender were utilized as control.The main measurements included the following biochemical measurements:-Ceruloplasmin (CP), copper(Cu),total protein(TP) ,albumin(Alb.),globulin(Glo),total cholesterol(TC), triglyceride(TG), and total bilirubin(TB) concentrations, also Alb./Glo. ratio, TC/Alb ratio, CP oxidase activity, CP oxidase specific activity and Cu conc. / CP oxidase activity ratio in sera of healthy (control) and patients with MI (history of DM , BP and DM+BP+smoking).The results revealed a highly significant increase(p&lt;0.001) in the CP, TP, Glo, TG, TB concentrations, Alb./Glo. ratio, CP oxidase activity, specific activity and Cu conc./CP oxidase activity ratio in sera of patients with MI (DM+ BP+smoking),while the same parameter referred significant increase(p&lt;0.01) in patients with MI(DM or BP) in comparisom with control group. But Alb. concentration show significant decrease in the all groups (p&lt;0.001), (p&lt;0.01) respectively. An important finding in this study is that biochemical risk factors appeared to occur in patients with DM+BP+smoking more the patients with DM or BP. This observation suggests that DM+BP+smoking may be more prominent risk factor for MI. Hypertriglyceridemia, but not hypercholesterolemia, is associated with MI. TC/Alb ratio is considered a better index of cardiovascular risk than serum cholesterol. CP conc., CP activity and specific activity and Cu Conc. / CP oxidase activity anew biochemical parameters and risk factors, therefore this results it is regarded us a primary indicator to MI.

Regulation of the oxidative processes as a possible mechanism of iron nanoparticles antitumor action.

e23160 Background: It has been shown that metal nanoparticles (NPs) can inhibit a tumor growth. Oxidative processes play important roles in tumor development and growth. The aim of this study was to determine parameters of oxidative stress in the blood of tumor-bearing animals depending on the antitumor effect of iron NPs (30-50 nm). Methods: Male rats with transplantable lymphosarcoma (LS) in the main group (n = 21) were treated with eight i.p. injections of iron NPs (total doses of 10 mg/kg bw), the control LS rats (n = 20) received saline i.p. The activity of catalase, superoxide dismutase (SOD), content of glutathione (GSH) and malondialdehyde (MDA) in the red blood cells (RBC) and ceruloplasmin oxidase activity (CP) and MDA content in blood plasma were measured. These parameters were analyzed in rats with complete tumor regression (n = 12) after NPs treated and in cases of tumor growth (n = 9). Results: In RBC of control group the level of GSH and catalase activity were increased compared to healthy rats by 24% and 14.3% (p &lt; 0.05), respectively. In spite of activation of the given antioxidant system components, the MDA content in RBC was increased by 45% (p &lt; 0.01) compared to normal values. In plasma of control group we observed an increase in MDA by 167.4% (p &lt; 0.01) and a decrease in CP by 36.8% (p &lt; 0.001). In the main group there was a decrease in blood MDA level and the antioxidant system reorganization. The degree of changes depended on the antitumor effect of NPs: rats with tumor growth showed a tendency to the decreasing MDA in RBC and normalization of plasma MDA; MDA in rats with LS regression was similar to normal values. In the main group the CP activity did not differ from the values in healthy rats. GSH increased in animals with tumor growth by 218.6% and in the animals with the effect - by 69% compared to normal values (p &lt; 0.01). SOD activity in the rats with LS growth increased by 42% and in the rats with LS regression it decreased by 30% (p &lt; 0.01). Conclusions: The data suggest the relationship between antitumor effect and modulating action on oxidative processes in LS rats treated by iron NPs. Iron NPs improved efficiency of antioxidant system in blood and contributed to suppression of oxidative stress associated with tumor growth.

New silver nanoparticles induce apoptosis-like process in E. coli and interfere with mammalian copper metabolism.

Silver nanoparticles (SNPs) are new functional materials that are widely used in biomedical and industrial technologies. Two main features that make SNPs valuable are their strong antibacterial effects and low toxicity to eukaryotes. In this study, SNPs were synthesized using a modified method of reducing the metal ions to their atomic state followed by crystallization. SNPs were characterized by UV/vis spectroscopy, X-ray diffractometry, atomic force microscopy, and transmission electron microscopy (TEM). The SNPs were spherically shaped with an average linear dimension of 20 nm. In aqueous solution, the SNPs were beige-yellow in color, and they formed a black color in bacteria-rich growth media. The toxicity and bioavailability of the SNPs were tested using Escherichia coli cells and C57Bl/6 mice. Although the SNPs displayed bactericidal activity, an E. coli cell strain transformed with an expression plasmid carrying a human CTR1 ectodomain with three motives that bind Cu(II), Cu(I), and Ag(I) demonstrated increased resistance to treatment with SNPs. TEM showed that the SNPs were absorbed by the E. coli cell, and flow cytometry showed that the SNPs induced apoptosis-like death. In mice treated with SNPs (daily intraperitoneal injection of 10 μg SNPs/g body weight over 4 days), the ceruloplasmin (Cp) oxidase activity in the blood serum decreased. However, level of Cp gene expression, the relative contents of the Cp protein in the Golgi complex and in the serum did not change. Treatment with SNPs did not influence the activity of superoxide dismutase 1 in the liver and had no apparent toxic effects in mice. These findings expand the scope of application for the use of new SNPs. The data are discussed in a paradigm, in which the effects of SNPs are caused by the interference of silver ions with copper metabolism.

Abstract 454: High Density Lipoprotein Proteome Dynamics is Altered in Non-alcoholic Fatty Liver Disease

Objectives: Nonalcoholic fatty liver disease (NAFLD) is associated with an increased rate of cardiovascular disease (CVD) related mortality. HDL protects against CVD through reverse cholesterol transport, anti-oxidant and anti-inflammatory functions. HDL functions and the proteome composition are altered in CVD. We used 2 H 2 O metabolic labeling approach to test hypothesis that altered HDL proteome dynamics is involved in HDL dysfunction in NAFLD. Methods: The kinetics of HDL proteins were measured in patients NAFLD (n=12) and healthy controls (n=8). Each subject consumed 2 H 2 O in their drinking water and blood samples were collected at different time points during one week. 2 H-enrichment of tryptic peptides from HDL proteins were analyzed by mass spectrometry. Oxidase activity of HDL-associated ceruloplasmin (Cp) and HDL’s inflammatory index were quantified using spectrophotometric assays. Results: Compared to control, NAFLD had higher BMI, Hba1c, HOMA-IR, plasma AST, ALT and triglycerides, but similar LDL and HDL cholesterol. NAFLD also had higher inflammatory index (1.8±0.5 vs 1.2±0.2 RUF/mgHDLc/min, p&lt;0.05) and oxidase activity of Cp (93.7±61.2 vs 61.2 U/L, p&lt;0.005). This was associated with increased serum actvity of MPO (6.2±1.2 vs 8.4±1.6, p&lt;0.05), a nutrophile-derived protein involved in HDL dysfunction. HDL NAFLD was significantly enriched with proteins involved in the acute phase response (complement 3, Cp) but depleted in apoAII and PON1. These changes were associated with increased fractional catabolic rates (FCRs) of apoAI (1.6±0.2 vs 1.1±0.3 %/h), apoAII (1.6±0.2 vs 1.1±0.3 %/h), apoAIV (2.6±0.8 vs 3.9±0.7%/h) and increased relative production rate (RPR) of complement 3 (&gt;4 fold). Oxidase activity of Cp was positively associated with FCR of apoAI (r=0.53, p=0.002) and RPR of C3 (r=0.32, p=0.03). Conclusions: HDL dysfunction in NASH could be related to the altered turnover of HDL proteins, including increased degradation of apoAI, apoAII, apoAIV and increased production of C3.

164. Improvement of Gene Therapy for Wilson Disease

Wilson's disease (WD) is an autosomal recessively inherited copper storage disorder due to mutations in ATP7B gene that causes hepatic and neurologic symptoms. Current treatments are based on lifelong copper chelating drugs, which may cause side effects and do not restore normal copper metabolism. We have recently demonstrated that the administration of an AAV vector expressing ATP7B under the control of a liver specific promoter induces full restoration of copper homeostasis in a mouse model of Wilson's disease. However, the size of the vector genome surpasses the optimal size for AAV packaging, limiting the use of large promoters or additional regulatory sequences such as introns or bigger poly A sequences. In the present work we have designed two truncated versions of ATP7B protein (T1 and T2), and have analyzed their functionality and therapeutic efficacy. ATP7B contains 6 metal binding sites (MBS) in the N-terminal region. T1 presents a deletion of 1 MBS and a fragment of the adjacent one, whereas T2 lacks the first 4 MBS. Both proteins were active since they were able eliminate intracellular excess of copper in an in vitro system. The administration of recombinant AAV vectors carrying the truncated proteins under the control of a liver specific promoter was able to reduce liver damage and urinary copper excretion in the murine model, but T1 was less efficient than the WT ATP7B gene. In contrast, T2 showed full capacity to normalize these parameters. Furthermore, T2 was more efficient than WT in restoring ceruloplasmin oxidase activity in serum. In conclusion, we have identified a fully functional truncated version of ATP7B protein that will reduce the size of the therapeutic AAV vector genome and allow the introduction of additional regulatory elements.

Effect of iron nanoparticles on free radical oxidation process in blood of rats with Pliss lymphosarcoma

The use of metal nanoparticles (NPs) for cancer treatment requires careful examination of their biological effects. The aim of this study was to determine parameters of oxidative processes in the blood of tumor-bearing animals treated with metallic iron NPs only. The markers of antioxidant status and accumulation of lipid peroxidation products were measured in erythrocytes and blood plasma of rats with Pliss lymphosarcoma (PLS) and intact rats. PLS animals were treated eight times with iron NPs (at a dose of 1.25 mg/kg bw (main group), rats of the control group received saline (0.3 ml). In control animals, an increase in malondialdehyde (MDA) was observed in red blood cells (RBC) by 45%; this was accompanied by compensatory increase in reduced glutathione (GSH) and catalase by 24% and 14.3%, respectively (p<0.05). In plasma an increase in MDA by 167.4% (p<0.01) and a decrease in oxidase activity of ceruloplasmin (CP) by 36.8% (p<0.001) were found. In the main group there was a decrease of accumulation of lipid peroxidation products in the blood. Intensity of detected changes depended on the antitumor effect: rats with growing LSP showed a tendency to the decrease in the RBC MDA level and normalization of plasma MDA; in animals with LSP regression this marker did not differ from normal values. In all animals of the main group the CP content was basically the same as in intact rats while GSH increased in the group without therapeutic effect (by 218.6%) and in the group with the effect by 69% (versus normal values; p<0.01). SOD activity in the rats with LSP growth significantly increased (by 42%), in the rats with regression decreased (by 30%) with subsequent normalization. Thus, administration of iron NPs caused activation of the antioxidant system in blood and a significant decrease in the manifestations of oxidative stress associated with tumor growth.

A Biochemical Study to Estimate Malonaldehyde and Ceruloplasmin Oxidase Activity As Parameters Express Oxidation – Antioxidation Balance for Patients With Acute Hepatitis Virus Type C

Oxygen free radicals play an important role in the pathogenesis of tissue damage in many pathological conditions, including liver diseases. Aim of the present study focused on the investigation the possible relationship between serum malondialdehyde level, an index of lipid peroxidation, and ceruloplasmin levels, as protective agent against lipid peroxidation, in hepatitis C virus. A group of 31 hepatitis virus type C patients enrolled in the study, while; control group consisted of 25 healthy subjects. In the present study, total proteins (g/L), malondialdehyde (µM), ceruloplasmin oxidase activity (U/L) and ceruloplasmin concentration (g/L) were measured in sera samples of patients with hepatitis C virus as well as in the healthy controls.

CERULOPLASMIN ACTIVITY AND ITS RELATION TO COPPER LEVEL IN BLOOD SERUM OF FRIESIAN DAIRY COWS.

The relationship between ceruloplasmin, a metalloenzyme with oxidase activity, and copper was investigated in Frisian dairy cows.The oxidase activity of ceruloplasmin correlated closely with the serum copper concentrations in Frisian dairy cows. Variations of copper (Cu) concentration and ceruloplasmin (Cp) activity in serum of dairy cows at different stages of lactation were assessed in 60 Frisian dairy cows. Furthermore, ceruloplasmin to copper ratios were also investigated. The cows were classified according to their lactation stages into three different groups as early lactation stage (4–6 weeks postpartum), mid-lactation stage (17–22 weeks postpartum) and late-lactation stage (25-30 weeks post-partum). Each group consisted of 20 multiparous cows. Serum samples were obtained from each cow for estimation of cereloplasmin activity and copper levels. Concentrations of serum copper (sCu) were higher in the group of early lactation stage than the other groups (P < 0.05). Serum cereloplasmin (sCp) activity also showed significant difference between early lactation, mid and late lactation groups (P < 0.05). The ratios of cereloplasmin activity to copper concentration (Cp/Cu) were significantly changed in the different lactation stages of dairy cows (P< 0.05). For evaluation of copper status, use of sCp/sCu identified more animals as ‘low’ and ‘marginal’. It can be concluded that ceruloplasmin and copper undergo a physiological increase justafter calving; thus, their values should be interpreted with caution during assessment of copper status. Further research is required to refine diagnosis criteria for use of such ratio in determining copper status in Frisian dairy cows.

Evolution of exchangeable copper and relative exchangeable copper through the course of Wilson's disease in the Long Evans Cinnamon rat.

BackgroundWilson's disease (WD) is an inherited disorder of copper metabolism leading to liver failure and/or neurological impairment. Its diagnosis often remains difficult even with genetic testing. Relative exchangeable copper (REC) has recently been described as a reliable serum diagnostic marker for WD.Methodology/Principal FindingsThe aim of this study was to validate the use of REC in the Long Evans Cinnamon (LEC) rat, an animal model for WD, and to study its relevance under different conditions in comparison with conventional markers. Two groups of LEC rats and one group of Long-Evans (LE) rats were clinically and biologically monitored from 6 to 28 weeks of age. One group of LEC rats was given copper-free food. The other groups had normal food. Blood samples were collected each month and different serum markers for WD (namely ceruloplasmin oxidase activity, exchangeable copper (CuEXC), total serum copper and REC) and acute liver failure (serum transaminases and bilirubinemia) were tested. Every LEC rat under normal food developed acute liver failure (ALF), with 40% global mortality. Serum transaminases and bilirubinemia along with total serum copper and exchangeable copper levels increased with the onset of acute liver failure. A correlation was observed between CuEXC values and the severity of ALF. Cut-off values were different between young and adult rats and evolved because of age and/or liver failure. Only REC, with values >19%, was able to discriminate LEC groups from the LE control group at every time point in the study. REC sensitivity and specificity reached 100% in adults rats.Conclusions/SignificanceREC appears to be independent of demographic or clinical data in LEC rats. It is a very simple and reliable blood test for the diagnosis of copper toxicosis owing to a lack of ATP7B function. CuEXC can be used as an accurate biomarker of copper overload.