Metals exert detrimental effects on various systems within the body, including the nervous system. Nevertheless, the dose-response relationship concerning the administration of low doses of metal ...mixtures remains inadequately explored. The assessment of neurotoxic effects of lead, cadmium, mercury, and arsenic mixture (MIX) administered at low dose ranges, was conducted using an in vivo approach. A subacute study was conducted on a rat model consisting of a control and five treatment groups subjected to oral exposure with gradually increasing doses (from MIX 1 to MIX 5). The results indicated that behavioural patterns in an already developed nervous system displayed a reduced susceptibility to the metal mixture exposure with tendency of higher doses to alter short term memory. However, the vulnerability of the mature brain to even minimal amounts of the investigated metal mixture was evident, particularly in the context of oxidative stress. Moreover, the study highlights superoxide dismutase's sensitivity as an early-stage neurotoxicity marker, as indicated by dose-dependent induction of oxidative stress in the brain revealed through Benchmark analysis. The narrowest Benchmark Dose Interval (BMDI) for superoxide dismutase (SOD) activity (1e-06 - 3.18e-05 mg As/kg b.w./day) indicates that arsenic may dictate the alterations in SOD activity when co-exposed with the other examined metals. The predicted Benchmark doses for oxidative stress parameters were very low, supporting “no-threshold” concept. Histopathological alterations were most severe in the groups treated with higher doses of metal mixture. Similarly, the brain acetylcholinesterase (AChE) activity demonstrated a dose-dependent decrease significant in higher doses, while BMDI suggested Cd as the main contributor in the examined metal mixture. These findings imply varying susceptibility of neurotoxic endpoints to different doses of environmentally relevant metal mixtures, advocating for risk assessment and regulatory measures to address metal pollution and enhance remediation strategies.
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•Only higher doses of metal mixture showed tendency for altered short term memory.•Superoxide dismutase is a marker for early stage of metal mixture neurotoxicity.•When co-exposed to Pb, Cd and Hg, As dictates changes in superoxide dismutase.•Metal mixture dose-dependently reduced acetylcholinesterase activity in brain.•Low benchmark doses for oxidative stress support metals' “no-threshold” concept.
Monocytes’ plasticity has an important role in the development of rheumatoid arthritis (RA), an autoimmune disease exhibiting greater prevalence in women. Contribution of this phenomenon to sex bias ...in RA severity was investigated in rat collagen-induced arthritis (CIA) model of RA. The greater severity of CIA in females (exhibiting signs of bone resorption) was accompanied by the higher blood level of advanced oxidation protein products and a more pro-oxidant profile. Consistently, in females, the greater density of giant multinuclear cells (monocytes/macrophages and osteoclasts) in inflamed joint tissue was found. This correlated with the higher frequencies of CCR2- and CX3CR1- expressing cells (precursors of inflammatory monocytes/macrophages and osteoclasts) among CD11b+ splenocytes. This in conjunction with the enhanced migratory capacity of CD11b+ monocytic cells in females compared with males could be linked with the higher frequencies of CCR2+CX3CR1-CD43
low
CD11b+ and CCR2-CX3CR1+CD43
hi
CD11b+ cells (corresponding to “classical” and “non-classical” monocytes, respectively) and the greater density of CD68+ cells (monocytes/macrophages and osteoclast precursors/osteoclasts) in blood and inflamed paws from female rats, respectively. Consistently, the higher levels of GM-CSF, TNF-α and IL-6, IL-1β (driving Th17 cell differentiation), and IL-17 followed by the lower level of IL-10 were measured in inflamed paw cultures from female compared with male rats. To the greater IL-17 production (associated with enhanced monocyte immigration and differentiation into osteoclasts) most likely contributed augmented Th17 cell generation in the lymph nodes draining arthritic joints from female compared with male rats. Overall, the study suggests the sex-specific contribution of monocytic lineage cells to CIA, and possibly RA development.
Breast cancer is at the forefront of female malignancy and the leading cause of cancer death among women. Gender, age, hormone therapy, smoking, exposure to endocrine disruptors and family history ...are significant breast cancer risk factors according to epidemiological data. Considering metalloestrogenic Cd property and a plethora of research work on hormone involvement in breast cancer the study aimed to determine Cd concentration in three compartments of breast cancer patients in relation to their blood hormone status. Further, as oxidative stress is a critical mechanism of Cd toxicity, the objective of this study was to determine potential changes in oxidative status homeostasis.
The study enrolled 55 patients with breast cancer diagnosis and 41 healthy women with benign breast changes. Concentration of Cd was determined using graphite furnace atomic absorption spectrometry.
Cadmium concentration in tumor tissue was significantly higher than control and almost four times higher than Cd concentration in the healthy surrounding tissue. Strong positive correlation was observed between Cd concentrations in changed breast tissue and FSH and LH levels, while the correlation was negative with estradiol level. Cancer patients had significantly increased blood total antioxidative status while total oxidative status did not significantly differ between study groups. The study revealed Cd implication in breast cancer onset following a significant odd ratio for Cd levels in changed tissue samples. Moreover, presented data confirmed sex hormone and oxidative status imbalance caused by Cd presence, closely related to cancer development.
•Almost 3.5 fold higher Cd levels measured in tumors than in healthy tissue.•Cd levels in breast tissue correlate with gonadotropins and estradiol levels.•Cd role in cancer breast partly mediated through endocrine disruptive properties.•Cd-induced redox status imbalance implicated in breast cancer development.
Purpose
End-stage renal disease patients on chronic hemodialysis (HD) have a shortened life expectancy compared to the general population. The aim of this study was to evaluate a possible link ...between three new and emerging factors in renal pathophysiology: Klotho protein, telomere length in peripheral blood mononuclear cells (TL) and redox status parameters before HD (bHD) and after HD (aHD), and to test mortality prediction capability of these emerging parameters in a population of HD patients.
Methods
The study included 130 adult patients with average age 66 (54–72), on HD (3 times per week; 4–5 h per session). Klotho level, TL, routine laboratory parameters, dialysis adequacy and redox status parameters: advanced oxidation protein products (AOPP), prooxidant–antioxidant balance (PAB), superoxide anion (O
2
.−
), malondialdehyde (MDA), ischemia-modified albumin (IMA), total sulfhydryl group content (SHG), and superoxide dismutase (SOD) were determined.
Results
Klotho concentration was significantly higher aHD; 68.2 (22.6–152.9) vs. bHD 64.2 (25.5–119.8) (
p
= 0.027). The observed increase in TL was not statistically significant. AOPP, PAB, SHG, and SOD activity were significantly increased aHD (
p
> 0.001). The patients with the highest mortality risk score (MRS) had significantly higher PAB bHD (
p
= 0.002). Significantly lower O
2
.−
(
p
< 0.001), SHG content (
p
= 0.072), and IMA (
p
= 0.002) aHD were found in patients with the lowest MRS values. Principal component analysis revealed redox balance-Klotho factor as a significant predictor of high mortality risk (
p
= 0.014).
Conclusion
Decreased Klotho and TL attrition as well as redox status disturbance could be connected with higher mortality rate in HD patients.
This study aimed to investigate the effect of 150 mg/L sodium fluoride (NaF) on redox status parameters and essential metals copper (Cu), iron (Fe), and zinc (Zn) in the blood, liver, kidney, brain, ...and spleen of Wistar rats and to determine the protective potential of selenium (Se) against fluoride (F
) toxicity. Male Wistar rats were randomly distributed in groups of five (n=5) receiving tap water (control) or water with NaF 150 mg/L, NaF 150 mg/L + Se 1.5 mg/L, and Se 1.5 mg/L solutions
for 28 days. Fluorides caused an imbalance in the redox and biometal (Cu, Fe, and Zn) status, leading to high superoxide anion (O
) and malondialdehyde (MDA) levels in the blood and brain and a drop in superoxide dismutase (SOD1) activity in the liver and its increase in the brain and kidneys. Se given with NaF improved MDA, SOD1, and O
in the blood, brain, and kidneys, while alone it decreased SH group levels in the liver and kidney. Biometals both reduced and increased F- toxicity. Further research is needed before Se should be considered as a promising strategy for mitigating F
toxicity.
Background and Objectives: Diabetic foot (DF) development is driven by complex interactions of hyperglycemia, inflammation, and oxidative stress (OS). We aimed to investigate OS and inflammatory ...biomarkers in patients with DF and their potential to improve early diagnosis and management of DF. Materials and Methods: The prooxidant−antioxidant balance (PAB), superoxide dismutase (SOD), total oxidative status (TOS), total sulfhydryl groups (SHG), routine biochemical parameters, and complete blood count were determined in 42 patients with type-2 DM, of which 23 patients had DF, while 19 patients were without DF complications. The neutrophils-to-lymphocyte ratio (NLR) was evaluated as a biomarker of inflammation. Results: Patients with DF had significantly higher (p < 0.05) PAB levels (170 ± 33.9 U/L) compared to those without DF complications (142 ± 31.3 U/L). In addition, patients with DF had significantly reduced SOD activities (p < 0.01). NLR values were significantly higher in the DF group (median: 2.8; interquartile range: 2.0−4.3) than in the group without DF (median: 1.4; interquartile range: 1.4−2.1; p < 0.01). A positive correlation was found between the PAB and NLR index (r = 0.449; p < 0.05). The diagnostic accuracy of both PAB (AUC = 0.741; p < 0.01) and NLR (AUC = 0.760; p < 0.01) was estimated as acceptable. Conclusions: In conclusion, the development of DF is associated with enhanced OS and inflammation processes. PAB and NLR could be useful non-invasive biomarkers of DF development.
Notwithstanding prevalence gaps in micronutrients supporting immune functions, the significance of their deficits/supplementation for the efficacy of vaccines is underinvestigated. Thus, the ...influence of supplementation combining vitamins C and D, zinc, selenium, manganese, and N-acetyl cysteine on immune correlates/surrogates of protection conferred by a quadrivalent influenza vaccine (QIV) in mice was investigated. The supplementation starting 5 days before the first of two QIV injections given 28 days apart increased the serum titres of total and neutralizing IgG against each of four influenza strains from QIV. Accordingly, the frequencies of germinal center B cells, follicular CD4+ T helper (Th) cells, and IL-21-producing Th cells increased in secondary lymphoid organs (SLOs). Additionally, the supplementation improved already increased IgG response to the second QIV injection by augmenting not only neutralizing antibody production, but also IgG2a response, which is important for virus clearance, through favoring Th1 differentiation as indicated by Th1 (IFN-γ)/Th2 (IL-4) signature cytokine level ratio upon QIV restimulation in SLO cell cultures. This most likely partly reflected antioxidant action of the supplement as indicated by splenic redox status analyses. Thus, the study provides a solid scientific background for further research aimed at repurposing the use of this safe and inexpensive micronutrient combination to improve response to the influenza vaccine.
Most Pb and Cd neurotoxicity studies investigate exposure to either of the toxic metals alone, while data on co-exposure are scarce. The aim of our study was to fill that gap by investigating acute ...combined effects of Pb and Cd on redox and essential metal status in the brain of Wistar rats. Animals were randomised in four groups of six to eight rats, which received 15 or 30 mg/kg of Cd, 150 mg/kg of Pb, or 150 mg/kg of Pb + 15 mg/kg of Cd by gavage. The fifth, control, group received distilled water only. Co-treatment with Pb and Cd induced significant increase in malondialdehyde (MDA) and thiobarbituric acid-reactive substances (TBARS) compared to control and groups receiving either metal alone. This is of special importance, as MDA presence in the brain has been implicated in many neurodegenerative disorders. The groups did not significantly differ in Zn, Cu, Mn, and Fe brain levels. Our findings highlight the importance of metal mixture studies. Neurotoxicity assessments of single chemicals do not provide a real insight into exposure to mixtures in real life. Further research should look into interactions between these metals to reveal complex molecular mechanisms of their neurotoxicity.
Objectives
The aim of our study was to analyze oxidative stress (OS) markers in multiple sclerosis (MS) patients during relapse and remission and to evaluate the effects of corticosteroid relapse ...treatment on oxidative status, and also to determine possible relationship between OS markers and relapse disability recovery after corticosteroid treatment.
Methods
Our study included 118 MS patients, (59 relapse/59 remission) 70 females and 48 males, mean age 40.2 ± 9.4 years, and 88 matched healthy controls. Undergoing disease-modifying therapy (DMT) was present in 30.5% of relapse and 88% of remission MS patients. We analyzed in plasma/serum the following: pro-oxidative–antioxidative balance (PAB), nitrates and nitrites (NO
3
+ NO
2
), malondialdehyde (MDA), advanced oxidation protein products (AOPP) superoxide dismutase (SOD), catalase (CAT), uric acid, bilirubin, albumin, and transferrin in all patients and additionally after corticosteroid relapse treatment. Neurological disability was measured using the Extended Disability Status Scale (EDSS).
Results
Better clinical recovery after relapse treatment was associated with increased baseline SOD, decreased AOPP, and ongoing DMT (all
p
< 0.05). There was no difference between OS markers in relapse and remission. MS patients had higher MDA, NO
3
+ NO
2
, PAB, SOD, CAT, lower AOPP, uric acid, albumin, bilirubin, and transferrin compared to controls (all
p
< 0.05). Corticosteroids caused significant decrease of all OS markers (all
p
< 0.05).
Conclusion
Increased baseline antioxidative activity of SOD and decreased baseline levels of pro-oxidant AOPP along with ongoing DMT were related to better clinical recovery after corticosteroid relapse treatment. Increase of pro-oxidants and antioxidant enzyme activity in relapse and remission confirms ongoing oxidative injury irrelevant of MS clinical presentation.
Telomeres are protective chromosomal ends. Short telomeres are a proven biomarker of biological aging. We aimed to find an association of telomere length and telomerase activity in circulating ...leukocytes and thromboaspirates of patients with acute myocardial infarction. Furthermore, association of the telomere-telomerase system with oxidative stress markers (as common risk factors for coronary artery disease (CAD)) was tested.
Patients were selected from the patients admitted to the intensive care unit with acute myocardial infarction with ST-segment elevation (STEMI), with the following inclusion criteria - STEMI patients between 18 and 80 years old of both genders and candidates for primary percutaneous coronary intervention, with infarction pain present for a maximum of 12 h. In all the patients leukocyte telomere length, telomerase activity and scores related to oxidative-stress status (Protective, Damage and OXY) were evaluated.
Patients were divided into different groups: with stable angina pectoris (AP) (
= 22), acute myocardial infarction with: STEMI (
= 93), non-obstructive coronary arteries (MINOCA) (
= 7), blood vessel rupture (
= 6) at three time points, and compared to the group of 84 healthy subjects. Telomerase activity was significantly higher in all CAD sub-groups compared to the control group (AP = 0.373 (0.355-0.386), STEMI = 0.375 (0.349-0.395), MINOCA = 0.391 (0.366-0.401), blood vessel rupture = 0.360 (0.352-0.385) vs. CG = 0.069 (0.061-0.081),
< 0.001), while telomeres were significantly shorter in STEMI, MINOCA and blood vessel rupture groups compared to the control group (STEMI = 1.179 (0.931-1.376), MINOCA = 1.026 (0.951-1.070), blood vessel rupture = 1.089 (0.842-1.173) vs. CG = 1.329 (1.096-1.624),
= 0.030. Values of OXY score were significantly higher in STEMI and MINOCA patients compared to the control group and AP patients (5.83 (4.55-7.54) and 10.28 (9.19-10.72) vs. 4.94 (3.29-6.18) and 4.18 (2.58-4.86),
< 0.001). Longer telomeres and higher telomerase activity were found in thromboaspirates, compared to the peripheral blood leukocytes in the same patients (1.25 (1.01-1.84) vs. 1.18 (0.909-1.516),
= 0.036; and 0.366 (0.367-0.379) vs. 0.366 (0.367-0.379),
< 0.001, respectively). In addition, telomere length and telomerase activity had good diagnostic ability to separate STEMI patients from healthy persons.
Leukocyte telomere length and telomerase activity can differentiate CAD patients from healthy persons, and relate CAD to oxidative stress.
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