Association between Vitamin D Status, Oxidative Stress Biomarkers and Viral Load in Human Immunodeficiency Virus Type 1 Infection.

BACKGROUND: The role of vitamin D in the pathophysiology of human immunodeficiency virus type 1 (HIV-1) infection is still unclear. OBJECTIVE: To evaluate the associations between vitamin D and immunological, virological, and oxidative stress biomarkers in individuals with human immunodeficiency virus type 1 (HIV-1) infection. METHODS: The serum levels of 25 hydroxyvitamin D [25(OH)D] were determined in 314 HIV-1- infected individuals and 127 controls and the values ≥30 ng/mL defined a vitamin D sufficient (VDS) status, and <30 ng/mL defined the presence of hypovitaminosis D (HD). Oxidative stress was evaluated with plasma levels of lipid hydroperoxides, advanced oxidation protein products (AOPP), carbonyl protein, nitric oxide metabolites (NOx), total radical-trapping antioxidant parameter (TRAP), and sulfhydryl groups of proteins. Plasma HIV-1 viral load and CD4+/CD8+ T cells were quantified. RESULTS: The 25(OH)D levels and vitamin D status did not differ between HIV-1-infected individuals and controls. Hydroperoxides and AOPP were higher (p<0.0001 and p=0.002, respectively), whereas TRAP, carbonyl protein, and NOx were lower in HIV-1-infected individuals than controls (p<0.0001). HIV-1-infected individuals with HD showed higher hydroperoxide levels than those with a VDS status (p=0.012) and controls (p=0.022), independent of ethnicity and antiretroviral therapy. A positive correlation between 25(OH)D ≥30 ng/mL and viral load was observed when expressed as the number of copies/mL (r=0.178, p=0.039), as well as log10 copies/mL (r=0.183, p=0.033). CONCLUSION: These results suggest the bimodal influence of vitamin D in the modulation of immune response in HIV-1 infection, considering its differential susceptibility to modulation of the various immune targets and pathways.

Vitamin D deficiency is associated with disability and disease progression in multiple sclerosis patients independently of oxidative and nitrosative stress.

The aim of this study was to assess vitamin D status in patients with multiple sclerosis (MS) and to evaluate whether it was associated with oxidative and nitrosative stress (O&NS) markers and disability. This study included 137 patients with MS and 218 healthy controls. The markers evaluated were serum levels of 25-hydroxyvitamin D, lipid hydroperoxides, advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), and total radical-trapping antioxidant parameter TRAP/UA. Patients with 25(OH)D<20ng/mL showed higher EDSS (p=0.016), MSSS (p=0.005) and lower AOPP (p=0.046) than those with 25(OH)D≥20ng/mL. After the binary logistic regression analyses, EDSS and MSSS remained significantly associated with vitamin D deficiency. We showed that lower levels of 25(OH)D were associated with higher EDSS and MSSS independently of variables such as O&NS, age, sex, body mass index, ethnicity, MS therapy, use of interferon beta, and clinical forms of MS (odds ratio: 1.380, 95% confidence interval 1.030-1.843, p=0.031). Moreover, the study showed an association between serum levels of 25(OH)D and EDSS (r2=0.115, p=0.002), demonstrating that 25(OH)D may contribute with 11.5% of increase in EDSS. Our results suggest that vitamin D deficiency may be considered one of the predictors of the disability in MS patients, independently of their redox status and influence the progression of disability in MS.

Disease progression and oxidative stress are associated with higher serum ferritin levels in patients with multiple sclerosis.

Hyperferritinemia and oxidative stress have been implicated in the pathogenesis of multiple sclerosis (MS). The aim of the present study was to evaluate the serum levels of ferritin and to verify their association with oxidative stress markers and MS progression. This study included 164 MS patients, which were divided in two groups according to their levels of ferritin (cut off 125.6µg/L). Oxidative stress was evaluated by tert-butyl hydroperoxide-initiated chemiluminescence (CL-LOOH), advanced oxidation protein products (AOPP), carbonyl protein, nitric oxide metabolites (NOx), sulfhydryl groups of protein and total radical-trapping antioxidant parameter (TRAP). MS patients with elevated levels of ferritin showed higher disease progression (p=0.030), AOPP (p=0.001), and lower plasma NOx levels (p=0.031) and TRAP (p=0.006) than MS patients with lower ferritin levels. The multivariate binary logistic regression analysis showed that increased AOPP and progression of disease were significantly and positively associated with increase of ferritin. The combination of serum ferritin levels and oxidative stress markers were responsible for 13,9% in the disease progression. In conclusion, our results suggest that ferritin could aggravate oxidative stress in patients with MS and contribute to progression of disease.

Albumin and Protein Oxidation are Predictors that Differentiate Relapsing-Remitting from Progressive Clinical Forms of Multiple Sclerosis.

The aim of the present study was to evaluate inflammatory, oxidative, and nitrosative stress (IO&NS) blood markers as possible predictors of multiple sclerosis (MS) and its clinical forms. This study included 258 MS patients (175 with relapsing-remitting MS (RRMS) and 83 with progressive MS clinical forms) and 249 healthy individuals. Peripheral blood samples were obtained to determine serum levels of albumin, ferritin, C-reactive protein (CRP), total protein, lipid hydroperoxide by tert-butyl hydroperoxide-initiated chemiluminescence (CL-LOOH), carbonyl protein content, advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), and total radical-trapping antioxidant parameter (TRAP). MS patients showed higher ferritin (p < 0.001) and CL-LOOH (p < 0.001) and lower albumin (p = 0.001), TRAP (p < 0.001), AOPP (p = 0.013), and NOx values (p < 0.001) than controls. Difference was not observed in CRP, total protein, and carbonyl proteins between patients and controls. In the logistic regression age-adjusted, ferritin and CL-LOOH showed positive association with MS and were predictors of MS development (OR: 1.006, 95 % CI: 1.003-1.009, p < 0.001 and OR: 1.029, 95 % CI: 1.007-1.052, p = 0.009, respectively). Albumin, TRAP, AOPP, and NOx were negatively associated with MS (p = 0.019, p = 0.003, p = 0.001, and p = 0.003, respectively). Moreover, other logistic regression age-adjusted showed that MS patients with progressive clinical forms had lower albumin and higher AOPP than those with RRMS (p = 0.037). In conclusion, ferritin, albumin, and biomarkers of IO&NS, such as CL-LOOH, AOPP, TRAP, and NOx were predictors of MS diagnosis, whereas albumin and AOPP were predictors that differentiated RRMS from the progressive clinical forms of MS.

Role of metabolic syndrome and antiretroviral therapy in adiponectin levels and oxidative stress in HIV-1 infected patients.

OBJECTIVE: HIV-1 infection is accompanied by severe metabolic and immune dysfunction. The aim of this study was to evaluate the role of metabolic syndrome (MetS) and antiretroviral therapy (ART) utilization on the adiponectin levels and oxidative stress in patients infected with HIV-1. METHODS: We allocated 285 patients into four groups: group 1: patients without MetS who were not using ART; group 2: patients without MetS using ART; group 3: patients with MetS who were not using ART; and group 4: patients with MetS using ART. Biochemical, immunologic, and oxidative stress parameters were measured. RESULTS: Group 4 exhibited higher lipoperoxides when compared with group 1 (P < 0.0001) and higher advanced oxidation protein products (AOPP) compared with group 2 or group 1 (P < 0.0001). Group 3 also presented higher AOPP than group 2 (P < 0.05). Group 4 showed lower adiponectin levels compared with groups 1 or 2 (P < 0.0001). Similarly, group 3 presented lower adiponectin levels compared with group 2 (P < 0.05) or group 1 (P < 0.0001). Multivariate analysis showed that both an increase in AOPP and a decrease in total radical-trapping antioxidant parameter/uric acid were independently associated with MetS in HIV-1 patients. Regarding immunologic markers of HIV-1 disease progression and viral replication, group 4 exhibited significantly higher CD45(+), CD3(+), and CD4(+) T cells count compared with group 2 (P < 0.01). CONCLUSION: HIV-1-infected patients with MetS exhibited hypoadiponectinemia and increased oxidative stress, and these findings were not influenced by ART use. The findings of the present study allow the suggestion that MetS and inflammation might be mainly responsible for the aforementioned features. More studies are needed to verify whether drugs or food, which yield increased adiponectinemia and decreased oxidative stress, could reduce cardiovascular risk in HIV-infected patients.

Impact of tumor removal on the systemic oxidative profile of patients with breast cancer discloses lipid peroxidation at diagnosis as a putative marker of disease recurrence.

BACKGROUND: Recent studies have suggested a regulatory role for some of the metabolites derived from oxidative stress in breast cancer. In this way, cancer-induced oxidative changes could modify the breast environment and potentially trigger systemic responses that may affect disease prognosis and recurrence. In this study, we investigated the systemic oxidative profile of women with early breast cancer bearing the primary tumor and after tumor withdrawal, and its long-term implications. PATIENTS AND METHODS: Plasma samples were collected at diagnosis, and the systemic oxidative profile was determined by evaluating the lipid peroxidation, total antioxidant capacity of plasma (TRAP), malondialdehyde (MDA), protein carbonylation, and hydroperoxides. Nitric oxide, vascular endothelial growth factor (VEGF), and tumor necrosis factor alpha (TNF-α) levels were further measured. We also evaluated the impact of the oxidative profiling at diagnosis on disease recurrence in a 5-year follow-up. RESULTS: Enhanced oxidative stress was detected in patients bearing the primary tumors, characterized by high lipid peroxidation, TRAP consumption, high carbonyl content, and elevated VEGF and TNF-α levels. After tumor removal, the systemic oxidative status presented attenuation in lipid peroxidation, MDA, VEGF, and TNF-α. The 5-year recurrence analysis indicated that all patients who recidivated presented high levels of lipid peroxidation measured by chemiluminescence at diagnosis. CONCLUSIONS: Our data suggest that the presence of the primary tumor is indicative of the systemic pro-oxidant status of breast cancer and demonstrates a role for lipid peroxidation in disease recurrence, highlighting the need for a metabolic follow-up of patients with cancer at diagnosis before tumor removal.