Diet and lifestyle habits: Association with cardiovascular disease indices in a Nigerian sub-population.

BACKGROUND: There is inadequate evidence regarding the pattern of unhealthy lifestyle behaviours in Nigeria hence the aim of this study was to assess the pattern of lifestyle-related habits that predispose to risk of cardiovascular disease (CVD) indices in a Nigerian population. METHODS: A population-based cross-sectional study was carried out on 422 apparently healthy males and females ≥18 years old. The World Health Organisation (WHO) STEPwise questionnaire was used to collect information on tobacco use or smoking habits, alcohol consumption and dietary habits. Logistic regression analysis was employed. RESULTS: 22.8% and 30.2% of participants indicated that someone smoked in their home and/or in closed areas at workplace, respectively, in the past 30 days. 225/422 admitted to taking alcohol including 72% within the past 12 months. 52.8% of the participants consumed <5 servings of fruits and/or vegetables each day. Results further showed that participants with <5 servings of fruits and/or vegetables (OR: 1.06, CI: 1.01-1.13, p = 0.028) and high level of alcohol consumption (OR: 1.85, CI: 1.18-2.88, p = 0.007) were more likely to have hypertension. CONCLUSIONS: The relatively high prevalence of alcohol consumption and apparent unhealthy diet are of huge concern given the increasing prevalence of CVD indices in the population.

Using chemiluminescence to determine whole blood antioxidant capacity in rheumatoid arthritis and Parkinson's disease patients.

The consequences of oxidative stress and inflammation are implicated in a wide range of diseases, including rheumatoid arthritis and Parkinson's disease. The status of antioxidant capacity in rheumatoid arthritis and Parkinson's disease remains unclear, in part due to common practice of assaying erythrocytes separately to plasma. This method removes any synergistic interactions between plasma and erythrocyte-based antioxidants. The experiments in this report tested antioxidant capacity in whole blood, erythrocytes and plasma by group and disease stage. Medically diagnosed patients were recruited along with appropriate control group participants. Fasting venous blood was assayed using chemiluminescence methods for: time to maximum light emitted, maximum light emitted, and plasma antioxidant capacity in vitamin E analogue units. Here we demonstrate that whole blood exhibits higher antioxidant capacity than either plasma or erythrocytes assayed separately. We report increased oxidative stress in the blood of rheumatoid arthritis patients by group (p = 0.018, p = 0.049). We show increased antioxidant capacity in Parkinson's disease patients by group (p < 0.001). For later stage Parkinson's disease patients, we report reduced oxidative stress (p = 0.025), and increased antioxidant capacity and for erythrocytes (p < 0.001, p = 0.004) and whole blood (p < 0.001, p = 0.003). Early stage Parkinson's disease showed higher antioxidant capacity on only one measure (p = 0.008). Whole blood chemiluminescence is a useful technique for determining redox status in disease and might help clarify the role of oxidative stress in rheumatoid arthritis and Parkinson's disease.

Cardiovascular disease risk factors in a Nigerian population with impaired fasting blood glucose level and diabetes mellitus.

BACKGROUND: Diabetes is a risk factor for cardiovascular diseases (CVDs) and there are reports of increasing prevalence of prediabetes in Nigeria. This study therefore characterised CVDs risk factors in subjects with impaired fasting glucose (IFG) and diabetes. METHODS: Data from 4 population-based cross-sectional studies on 2447 apparently healthy individuals from 18 - 89 years were analysed. Anthropometric, blood pressure and biochemical parameters were collected and classified. Individuals with IFG (prediabetes) and diabetes were merged each for positive cases of dyslipidaemia, high blood pressure (HBP) or obesity. Optimal Discriminant and Hierarchical Optimal Classification Tree Analysis (HO-CTA) were employed. RESULTS: Overall prevalence of IFG and diabetes were 5.8% (CI: 4.9 - 6.7%) and 3.1% (CI: 2.4 - 3.8%), respectively. IFG co-morbidity with dyslipidaemia (5.0%; CI: 4.1 - 5.8%) was the highest followed by overweight/obese (3.1%; CI: 2.5 - 3.8%) and HBP (1.8%; CI: 1.3 - 2.4%). The predicted age of IFG or diabetes and their co-morbidity with other CVD risk factors were between 40 - 45 years. Elevated blood level of total cholesterol was the most predictive co-morbid risk factor among IFG and diabetes subjects. Hypertriglyceridaemia was an important risk factor among IFG-normocholesterolaemic-overweight/obese individuals. CONCLUSION: The higher prevalence of co-morbidity of CVD risk factors with IFG than in diabetes plus the similar age of co-morbidity between IFG and diabetes highlights the need for risk assessment models for prediabetes and education of individuals at risk about factors that mitigate development of diabetes and CVDs.

Association between metabolic syndrome and 10-year risk of developing cardiovascular disease in a Nigerian population.

BACKGROUND: Prevalence of metabolic syndrome (MetS) and consequential cardiovascular disease (CVD) events are on the increase in Nigeria. The study aimed to identify the prevalence of 10-year CVD risk in a Nigerian population and assess its relationship with different indices of MetS. METHOD: A cross-sectional study was carried out on apparently healthy persons aged 18 years of age or older. Ten-year risk was calculated using the ATPIII/Framingham criteria. Subjects with risk score <10% were considered as having low risk, 10-20% moderate risk and >20% at high risk of developing CVD in 10 years. MetS was defined based on the Joint Scientific Statement on Harmonizing the MetS. RESULT: Of the 211 subjects, mean age was 51.3±17.3 years. Average risk of developing CVD in the next 10 years was 3.7±5.3%. Prevalence of low, moderate and high risk of developing CVD among study participants was 86.3% (95% CI 82.0-91.3%), 11.8% (95% CI 6.9-16.1%) and 1.9% (95% CI 0.0-3.8%), respectively. Prevalence of MetS was 26.7% (95% CI 21.0-33.3%). There was poor agreement between MetS and the CVD risk scores (kappa=0.209, p=0.001) CONCLUSIONS: The results showed that complementary use of MetS and CVD risk score is imperative, as there is indication of risk in individuals without MetS. Also a large proportion of the study population requires lifestyle intervention. These findings provide the evidence necessary to tailor public health interventions in this population, especially towards younger age groups.

Hemorheological parameters better classify metabolic syndrome than novel cardiovascular risk factors and peripheral vascular disease marker.

The present study compares the association of Metabolic Syndrome (MetS) with hemorheological parameters, oxidative stress, inflammation and peripheral arterial disease markers. 100 participants were recruited and participants were divided into three groups on the basis of absence or presence of MetS and its components. Odds ratio for correctly predicting MetS was highest for erythrocyte aggregation followed by erythrocyte deformability. ROC curve analysis demonstrated that all the hemorheological components significantly classified MetS participants. Area Under Curve was higher for the hemorheological parameters (erythrocyte aggregation and erythrocyte deformability) than for the oxidative stress, inflammation and peripheral arterial disease markers. The possibilities of the hemorheological components to be identified as better cardiovascular risk markers due to their strong association with MetS cannot be precluded from the present findings.

Maximum accuracy obesity indices for screening metabolic syndrome in Nigeria: A consolidated analysis of four cross-sectional studies.

BACKGROUND: In sub-Saharan Africa, there is no precise use of metabolic syndrome (MetS) definitions and risk factors screening indices in many clinical and public health services. Methods proposed and used in Western populations are adopted without validation within the local settings. The aim of the study is to assess obesity indices and cut-off values that maximise screening of MetS and risk factors in the Nigerian population. METHOD: A consolidated analysis of 2809 samples from four population-based cross-sectional study of apparently healthy persons≥18 years was carried out. Optimal waist circumference (WC) and waist-to-height ratio (WHtR) cut points for diagnosing MetS and risk factors were determined using Optimal Data Analysis (ODA) model. The stability of the predictions of the models was also assessed. RESULTS: Overall mean values of BMI, WC and WHtR were 24.8±6.0kgm(-2), 84.0±11.3cm and 0.52±0.1 respectively. Optimal WC cut-off for discriminating MetS and diabetes was 83cm in females and 85cm in males, and 82cm in females and 89cm in males, respectively. WC was stable in discriminating diabetes than did WHtR and BMI, while WHtR showed better stability in predicting MetS than WC and BMI. CONCLUSION: The study shows that the optimal WC that maximises classification accuracy of MetS differs from that currently used for sub-Saharan ethnicity. The proposed global WHtR of 0.50 may misclassify MetS, diabetes and hypertension. Finally, the WC is a better predictor of diabetes, while WHtR is a better predictor of MetS in this sample population.

Association of physical activity with metabolic syndrome in a predominantly rural Nigerian population.

AIMS: Physical activity is an essential determinant of health. However, there is dearth of evidence regarding prevalence of physical activity in developing countries, especially its association with metabolic syndrome risk factors. This study assessed the association of physical activity with metabolic syndrome in a Nigerian population. MATERIALS AND METHODS: A cross-sectional study was carried out on apparently healthy persons who are ≥ 18 years old. The World Health Organisation (WHO) Global Physical Activity Questionnaire (GPAQ) was used to collect five domains of physical activity. Participants were classified as physically active or inactive based on meeting the cut-off value of 600 MET-min/week. Metabolic syndrome was diagnosed using the Joint Scientific Statement on Harmonizing the Metabolic Syndrome criteria. RESULTS: Overall prevalence of physically active individuals was 50.1% (CI: 45.6-54.7%). Physical inactivity is significantly more in females (p<0.01) and among participants >40 years old (p<0.0001). Whereas individuals with metabolic syndrome appeared more likely to be physically active (OR=1.48, CI: 0.71-3.09); physical inactivity showed to exist more among participants who were living in urban area (OR=6.61, CI: 3.40-12.85, p<0.001). Participants with prediabetes (OR=1.69, CI: 0.62-4.61) and diabetes (OR=1.91, CI: 0.65-5.63) were more likely to be physically inactive as compared to other metabolic syndrome risk factors. CONCLUSION: The high prevalence of physical inactivity in this study population is a clear indication that concerted efforts to improve physical activity may be required. However, it seems that metabolic syndrome is not improved by being physically active. This suggests that interventions directed at physical activity alone may not produce optimal efficacy in this study population.

Association of abnormal erythrocyte morphology with oxidative stress and inflammation in metabolic syndrome.

In carrying out their role of free radical scavenging, erythrocytes become damaged due to oxidation of membrane lipids and proteins. Such damage may change the morphology of the erythrocytes. The present study aims to demonstrate change in erythrocyte morphology in MetS and associate the changes with increased oxidative stress and inflammation that were shown in our recent study. One hundred participants were recruited from a rural town of Australia. Whole blood viscosity, erythrocyte aggregation, erythrocyte deformability, lipid profile and blood sugar level, oxidative stress markers (erythrocyte reduced glutathione, superoxide dismutase, urinary isoprostanes) and inflammatory markers (high sensitivity C-reactive protein) were measured. Erythrocyte morphological study was performed by scanning electron microscopy. Recruited participants were classified into MetS and non-MetS following the National Cholesterol Education Program Adult Treatment Panel III definition. Data were analyzed by IBM SPSS 20 software. The mean percentages of biconcave cells were decreased whereas acanthocytes, stomatocytes and echinocytes were increased in MetS group compared to healthy controls. Morphologically abnormal erythrocytes were significantly correlated with oxidative stress and chronic inflammation markers. Free radicals generated in increased concentration in MetS seem to damage erythrocyte changing its morphology which possibly could affect other hemorheological parameters.

Association of altered hemorheology with oxidative stress and inflammation in metabolic syndrome.

OBJECTIVE: We have shown increased whole blood viscosity (WBV), decreased erythrocyte deformability, and increased erythrocyte aggregation in metabolic syndrome (MetS) in our previous study. The objective of the study was to find out if the altered hemorheology shown in MetS in our previous study is associated with chronic inflammation and oxidative stress in the same subjects. METHODS: One hundred recruited participants were classified into three groups based on the number of the MetS components present following National Cholesterol Education Program, Adult Treatment Panel III definitions. WBV, erythrocyte aggregation, erythrocyte deformability, oxidative stress markers (erythrocyte reduced glutathione (GSH), superoxide dismutase (SOD), and urinary isoprostanes), inflammatory markers high-sensitivity C-reactive protein (hsCRP), and thrombotic marker D-dimer were measured. Data were analyzed by IBM SPSS 20 software. RESULTS: We found a significant association of altered hemorheology with chronic inflammation and oxidative stress in MetS. There was a linear increase in the level of hsCRP and a linear decrease in the level of SOD and GSH across the quartiles of erythrocyte aggregation. Similarly, the thrombotic marker D-dimer showed a linear increase and oxidative stress marker GSH showed a linear decrease trend across the quartiles of WBV. DISCUSSION: Alterations of hemorheology in MetS are probably due to the effect of chronic inflammation and oxidative stress. The negative effects of chronic inflammation and oxidative stress on the cardiovascular system could be due to the resulting altered hemorheology.

Cardiovascular risks in prediabetes: preliminary data on "vasculopathy triad".

BACKGROUND: Subclinical cardiovascular disease is inherent in complications of diabetes mellitus. It occurs before the obvert manifestation of cardiovascular disease complication in diabetes, and involves vasculopathy triad or three major vascular events comprising stasis, endothelial dysfunction, and atherothrombosis. AIM: This study was to examine evidence of vasculopathy triad in prediabetes, biomarkers of stasis, endothelial dysfunction, and atherothrombosis in prediabetes were compared with apparently healthy group. MATERIALS AND METHODS: Eighty-one participants with results for plasma D-dimer, homocysteine, and whole blood viscosity were selected from a research database. The participants consisted of control (n = 44) and prediabetes (n = 37) based on clinical history and laboratory results. RESULTS: Multivariate analysis shows a significantly higher level of vasculopathy in prediabetes than in the control group (P > 0.0001). Blood viscosity (P < 0.04) and homocysteine (P < 0.03) are significantly higher in prediabetes than in controls. Average levels for plasma D-dimer are also higher in prediabetes than in control, but not statistically significant in this particular analysis. CONCLUSION: This study suggests a novel application of known idea, vasculopathy triad that could be used for assessment of subclinical cardiovascular disease in prediabetes.

Hemorheology, ankle brachial pressure index (ABPI) and toe brachial pressure index (TBPI) in metabolic syndrome.

INTRODUCTION: Microvascular dysfunction is associated with metabolic syndrome (MetS) and its components. The objective of our study was to assess macro and microvascular abnormalities in MetS and compare the strength of association of the ankle brachial pressure index (ABPI), toe brachial pressure index (TBPI) and hemorheological parameters with MetS. MATERIALS AND METHODS: 100 participants were recruited from a rural Australian town. Anthropometric measurements were taken along with blood pressures (BP) at the arm, the ankle and the big toe for calculating ABPI and TBPI. Whole blood viscosity (WBV), erythrocyte aggregation, erythrocyte deformability, lipid profile and blood sugar level were analyzed. Recruited participants were classified into MetS and non-MetS following National Cholesterol Education Program Adult Treatment Panel III definition. Data were analyzed by IBM SPSS 20 software. RESULTS: WBV and erythrocyte aggregation were higher whereas erythrocyte deformability was lower in participants with MetS when compared to participants without MetS. Age, sex and diabetes mellitus adjusted odds ratio for predicting MetS was not significant for ABPI and TBPI whereas it was significant for hemorheological parameters. Receiver Operating Characteristics curve showed that TBPI better classified MetS than ABPI but association of hemorheological parameters was superior to that of ABPI and TBPI with MetS. CONCLUSIONS: Both microcirculation defects and macrovascular circulation defects were present in MetS. The concurrences of the components of MetS could have an additive effect in enhancing alterations in hemorheological parameters which may give rise to severe microvasculopathy. The association of hemorheological parameters was stronger than the association of TBPI and ABPI with MetS.

Erythrocyte aggregation and metabolic syndrome.

Erythrocyte aggregation has been consistently associated with insulin resistance, central obesity and hypertension in the literature. Oxidative stress and chronic inflammation are almost always present in metabolic syndrome (MetS). Prooxidants and adipocytokines generated in MetS alter erythrocyte morphology, decrease erythrocyte deformability and increase whole blood viscosity (WBV). Increased WBV has been attributed to erythrocyte aggregation which in turn is greatly influenced by other rheological parameters, including its membrane surface charge and plasma fibrinogen concentration. The interplay of hemorheological factors, oxidative stress and inflammation has a detrimental effect in MetS due to the gross disturbance in microcirculation. The hemodynamic aspect of MetS needs further research and exploration.

Erythrocyte morphology in metabolic syndrome.

The study of erythrocyte morphology is of great importance in the field of hemorheology as the deformability of the circulating cells has a fundamental influence on the rheological properties of the blood. Diabetes mellitus, hypertension, dyslipidemia and obesity (mostly central obesity) are the major components of metabolic syndrome. In this review, we focus on the changes in erythrocyte morphology in different components of metabolic syndrome and also discuss the erythrocyte morphology in regards to oxidative stress - a common state of chronic diseases. This article also addresses the problem of inconsistency in the use of nomenclature and technique to identify the abnormal morphology and we recommend the use of standard terminology by all authors.

Atherothrombosis and oxidative stress: the connection and correlation in diabetes.

BACKGROUND: Hyperglycaemia-induced depletion of reduced glutathione (GSH) causes erythrocyte oxidative stress (EOS), which leads to vascular events including exacerbation of thrombotic events evidenced by changes in D-dimer level. It would, therefore, appear that there is a complex link between GSH and D-dimer, which are part of an emerging array of biomarkers associated with diabetes. The objective of this study was to investigate evidence of correlation between levels of plasma D-dimer and erythrocyte GSH in diabetes disease progression. SUBJECTS AND METHODS: A cohort of 69 subjects were selected based on medical history plus clinical findings and equally divided into control, prediabetes and diabetes groups, matched for age and sex. Plasma D-dimer and erythrocyte reduced glutathione (GSH) were determined and separated into quartiles as a means of indicating disease severity. Statistical analysis was by Pearson's correlation coefficient. RESULTS: Of the three groups, only the diabetes group showed any correlation between GSH and D-dimer. Of importance is that for increasing GSH, the second quartile range of GSH (xbar +/- SD = 45 +/- 22 mg/100ml) showed a statistically significant negative correlation for ranked D-dimer (xbar +/- SD = 1055 +/- 828 microg/l; r = -0.88; P < 0.02). The fourth quartile GSH range (xbar +/- SD = 79 +/- 40 mg/100 ml) showed a statistically significant positive correlation with D-dimer (xbar +/- SD = 1055 +/- 828 microg/l; r = 0.91; P < 0.02). Thus, within the diabetes group only, the increasing level of oxidative stress as measured by GSH first indicates a reduction in D-dimer followed by a rise in D-dimer, which led to the proposal of a two-part process of atherosclerosis that reconciles previous contradictory findings. CONCLUSIONS: This study provides not only evidence of a correlation between oxidative stress level and fibrinolysis in diabetes, but also an explanation of why previous studies have found both hypo- or hyperfibrinolysis associated with diabetes.

The 'vitamin E regeneration system' (VERS) and an algorithm to justify antioxidant supplementation in diabetes--a hypothesis.

In studies of vitamin E effectiveness in diabetes, there are still controversies surrounding negative observational and positive experimental results. However, there is no controversy that antioxidant vitamin E is regenerated from its pro-oxidant tocopheroxyl radical by a network of interacting co-antioxidants. The network of interacting co-antioxidants has only been studied individually. The hypothesis we propose is that a vitamin E regeneration system (VERS) model based on the complex interactions of the co-antioxidants provides a rationale for vitamin E supplementation as a therapeutic adjunct in diabetes. Furthermore, the factors considered prior to the use of Vitamin E as a supplement in diabetes research and therapy, the effectiveness of vitamin E supplementation and the limitations have been identified in the literature. There is no single study of vitamin E supplementation or efficacy that has determined vitamin E levels in combination with all of the co-antioxidants that interact to regenerate oxidised vitamin E. Therefore, there is a lack of good evidence for or against vitamin E being unilaterally depleted in the antioxidant network. There is also lack of rationale for choice of co-antioxidant supplementation. In essence, the normal conditions for effective antioxidant activity of vitamin E supplementation have yet to be fully explored. We propose a coherent model of VERS, and recommend that VERS status needs to be assessed, as part of evidence-based clinical practice to determine whether vitamin E should be recommended for the diabetic patient. We also propose an algorithm, based on the antioxidant activity and confounding factors, to guide the formulation of a credible hypothesis for clinical trials in assessing the function of vitamin E and treatment outcomes. The proposed model hinges on pertinent questions that have to be addressed to avoid organising a clinical trial that has been identified as biased.

D-dimer identifies stages in the progression of diabetes mellitus from family history of diabetes to cardiovascular complications.

AIM: The aim of the study was to ascertain whether there is variation in the fibrinolytic/coagulation component of diabetes associated with disease progression to macrovascular complications and whether D-dimer can discriminate such variation. METHODS: A total of 343 participants were selected based on clinical status and divided into 7 groups: control, family history of diabetes, pre-diabetes with/without CVD, diabetes with/without CVD and CVD only. Plasma D-dimer was tested. Statistical analysis was performed on log normalised data by ANOVA, Fisher's LSD post hoc test. After the initial analysis, data were classified and re-analysed by quartiles, interquartile range and 95(th) percentile. RESULTS: An overall significant difference between groups (p<0.002) and a steady rise in D-dimer levels that became increasingly higher than control as the disease progressed from pre-diabetes to cardiovascular complications was observed. A statistically significant difference was observed between control versus diabetes (p<0.0005). Analysis of data by quartiles and percentiles gave qualitatively similar results, but a greater significant difference between control versus pre-diabetes at 3rd quartile and interquartile range (p<0.014). CONCLUSION: We report changes in D-dimer levels that may indicate diabetes disease progression to macrovascular complications. Using D-dimer in conjunction with other biomarkers to identify stages of disease progression, commencing from pre-diabetes and continuing to development of asymptomatic and clinical cardiovascular disease in diabetes mellitus, is worthy of consideration.

Erythrocyte oxidative damage in chronic fatigue syndrome.

BACKGROUND: It has been hypothesized that a link exists between erythrocyte metabolism (particularly redox metabolism) and erythrocyte shape and that both are related to erythrocyte deformability. The aim of this research is to confirm the results of earlier studies and to investigate a correlation between erythrocyte morphology and erythrocyte oxidative damage in chronic fatigue syndrome (CFS). METHODS: Reduced glutathione (GSH), malondialdehyde (MDA), methemoglobin (metHb) and 2,3-diphosphoglyceric acid (2,3-DPG) were measured in 31 patients suffering from CFS and 41 healthy control subjects. Scanning electron microscopic studies of the erythrocytes from both groups were also carried out. RESULTS: There was evidence of oxidative damage in CFS with statistically significant increases in 2,3-DPG (p < 0.05), metHb (p < 0.005) and MDA (p < 0.01). The CFS patients in this study also had significantly more stomatocytes in their blood than the normal subjects (p < 0.005). CONCLUSIONS: There is a strong likelihood that the increase in erythrocyte antioxidant activity is associated with the presence of stomatocytes. The results of this study provide further evidence for the role of free radicals in the pathogenesis of CFS and a link between erythrocyte metabolism and erythrocyte shape.

Changes in the erythrocyte glutathione concentration in the course of diabetes mellitus.

This study aims to evaluate the significance of the changes of erythrocyte reduced glutathione (GSH) in the course of diabetes mellitus including the pre-diabetes stage and cardiovascular disease co-morbidity. A total of 222 participants (female:male, 107:115) were selected and their erythrocyte GSH levels were measured. The participants were divided into four groups: (i) control; (ii) those with blood glucose level > or =5.6 mmol/l but < 6.9 mmol/l as pre-diabetes mellitus with no other pathology; (iii) diabetes without co-morbidity; and (iv) those with diabetes mellitus and cardiovascular disease. Statistical analysis was by ANOVA followed by a Fisher's LSD post hoc test. We observed that GSH concentration was significantly different between groups (P < 0.04). The Fisher's post hoc test indicated significant differences in erythrocyte GSH levels between the pre-diabetes mellitus and diabetes mellitus groups compared to control (P < 0.005 and P < 0.05, respectively). A statistically significant change (P < 0.001) involving an initial fall followed by a rise in erythrocyte GSH levels was observed when diabetes mellitus and diabetes mellitus+cardiovascular disease groups were combined and assessed with respect to period of diabetes. We conclude that oxidative stress is already present in the pre-diabetes stage as determined by the fall in GSH, representing the initial phase of oxidative stress in diabetes mellitus progression. This finding provides evidence that antioxidant markers such as GSH could be a useful tool for pre-diabetes mellitus screening.

Cyclosporine A-induced changes to erythrocyte redox balance is time course-dependent.

Cyclosporine A-treated transplant recipients develop pronounced cardiovascular disease and have increased oxidative stress and altered antioxidant capacity in erythrocytes and plasma. These experiments investigated the time-course of cyclosporine A-induced changes to redox balance in plasma and erythrocytes. Rats were randomly assigned to either a control or cyclosporine A-treated group. Treatment animals received 25 mg/kg of cyclosporine A via intraperitoneal injection for either 7 days or a single dose. Control rats were injected with the same volume of the vehicle. Three hours after the final injections, plasma was analysed for total antioxidant status, alpha-tocopherol, malondialdehyde, and creatinine. Erythrocytes were analysed for reduced glutathione (GSH), alpha-tocopherol, methaemoglobin, malondialdehyde, and the activities of superoxide dismutase, catalase, GSH peroxidase, and glucose-6-phosphate dehydrogenase (G6PD). Cyclosporine A administration for 7 days resulted in a significant increase (P<0.05) in plasma malondialdehyde, methaemoglobin, and superoxide dismutase and catalase activities. There was a significant decrease (P<0.05) in erythrocyte GSH concentration and G6PD activity in cyclosporine A animals. There were no significant differences (P>0.05) between groups following a single dose of cyclosporine A in any of the measures. In summary, cyclosporine A alters erythrocyte redox balance after 7 days administration, but not after a single dose.

Cyclosporine A induced changes to plasma and erythrocyte antioxidant defences.

Organ transplant recipients develop pronounced cardiovascular disease, and decreased antioxidant capacity in plasma and erythrocytes is associated with the pathogenesis of this disease. These experiments tested the hypothesis that the immunosuppressant cyclosporine A (CsA) alters erythrocyte redox balance and reduces plasma antioxidant capacity. Female Sprague-Dawley rats were randomly assigned to a control or CsA treated group. Treatment animals received 25 mg/kg/day of CsA via intraperitoneal injection for 18 days. Control rats were injected with the same volume of the vehicle. Three hours after the final CsA injection, rats were exsanguinated and plasma analysed for total antioxidant status (TAS), alpha-tocopherol, malondialdehyde (MDA), and creatinine. Erythrocytes were analysed for superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glucose-6-phosphate dehydrogenase (G6PD) activities, alpha-tocopherol, and MDA. CsA administration resulted in a significant (P < 0.05) decrease in plasma TAS and significant increases (P < 0.05) in plasma creatinine and MDA. Erythrocyte CAT was significantly (P < 0.05) increased in CsA treated rats compared to controls. There were no significant differences (P > 0.05) in erythrocyte SOD, GPX, G6PD, alpha-tocopherol or MDA between groups. In summary, CsA alters erythrocyte antioxidant defence and decreases plasma total antioxidant capacity.