Associations among environmental exposure to trace elements and biomarkers of early kidney damage in the pediatric population.

BACKGROUND: In kidney damage, molecular changes can be used as early damage kidney biomarkers, such as Kidney Injury Molecule-1 and Neutrophil gelatinase-associated lipocalin. These biomarkers are associated with toxic metal exposure or disturbed homeostasis of trace elements, which might lead to serious health hazards. This study aimed to evaluate the relationship between exposure to trace elements and early damage kidney biomarkers in a pediatric population. METHODS: In Tlaxcala, a cross-sectional study was conducted on 914 healthy individuals. The participants underwent a medical review and a socio-environmental questionnaire. Five early damage kidney biomarkers were determined in the urine with Luminex, and molybdenum, copper, selenium, nickel, and iodine were measured with ICP-Mass. RESULTS: The eGFR showed a median of 103.75 mL/min/1.73 m2. The median levels for molybdenum, copper, selenium, nickel, and iodine were 24.73 ng/mL, 73.35 ng/mL, 4.78 ng/mL, 83.68 ng/mL, and 361.83 ng/mL, respectively. Except for molybdenum and nickel, the other trace elements had significant associations with the eGFR and the early kidney damage biomarkers. Additionally, we report the association of different exposure scenarios with renal parameters. DISCUSSION: and Conclusions. Among the explored metals, exposure to Cu and iodine impairs renal function. In contrast, Se may manifest as a beneficial metal. Interactions of Mo-Se and Mo-Iodine seem to alter the expression of NGAL; Mo-Cu for CLU; Mo-Cu, Mo-Se, and Mo-iodine for Cys-C and a-1MG; and Mo-Cu and Mo-iodine for KIM-1; were noticed. Our study could suggest that trace element interactions were associated with early kidney damage biomarkers.

Effect of smoking on the redox status of knee osteoarthritis: A preliminary study.

Even though smoking has been scarcely studied in osteoarthritis (OA) etiology, it is considered a controversial risk factor for the disease. Exposure to tobacco smoke has been reported to promote oxidative stress (OS) as part of the damage mechanism. The aim of this study was to assess whether smoking increases cartilage damage through the generation of OS. Peripheral blood (PB) and synovial fluid (SF) samples from patients with OA were analyzed. The samples were stratified according to smoking habit, Kellgren-Lawrence score, pain, and cotinine concentrations in PB. Malondialdehyde (MDA), methylglyoxal (MGO), advanced protein oxidation products (APOPs), and myeloperoxidase (MPO) were assessed; the activity of antioxidant enzymes such as gamma-glutamyl transferase (GGT), glutathione S-transferase (GST) and catalase (CAT), as well as the activity of arginase, which favors the destruction of cartilage, was determined. When stratified by age, for individuals <60 years, the levels of MDA and APOPs and the activity of MPO and GST were higher, as well as antioxidant system activity in the smoking group (OA-S). A greater degree of pain in the OA-S group increased the concentrations of APOPs and arginase activity (P < 0.01 and P < 0.05, respectively). Arginase activity increased significantly with a higher degree of pain (P < 0.01). Active smoking can be an important risk factor for the development of OA by inducing systemic OS in young adults, in addition to reducing antioxidant enzymes in older adults and enhancing the degree of pain and loss of cartilage.

Inflammation- and cancer-related microRNAs in rat renal cortex after subchronic exposure to fluoride.

The proximal tubule is a target of subchronic exposure to fluoride (F) in the kidney. Early markers are used to classify kidney damage, stage, and prognosis. MicroRNAs (miRNAs) are small sequences of non-coding single-stranded RNA that regulate gene expression and play an essential role in developing many pathologies, including renal diseases. This study aimed to evaluate the expression of Cytokine-Chemokine molecules (IL-1α/1ß/4/6/10, INF-γ, MIP-1α, MCP-1, RANTES, and TGF ß1/2/3) and inflammation-related miRNAs to evidence the possible renal mechanisms involved in subchronic exposure to F. Total protein and miRNAs were obtained from the renal cortex of male Wistar rats exposed to 0, 15 and 50 mg NaF/L through drinking water during 40 and 80 days. In addition, cytokines-chemokines were analyzed by multiplexing assay, and a panel of 77 sequences of inflammatory-related miRNAs was analyzed by qPCR. The results show that cytokines-chemokines expression was concentration- and time-dependent with F, where the 50 mg NaF/L were the main altered groups. The miRNAs expression resulted in statistically significant differences in thirty-four miRNAs in the 50 mg NaF/L groups at 40 and 80 days. Furthermore, a molecular interaction network analysis was performed. The relevant pathways modified by subchronic exposure to fluoride were related to extracellular matrix-receptor interaction, Mucin type O-glycan biosynthesis, Gap junction, and miRNAs involved with renal cell carcinoma. Thus, F-induced cytokines-chemokines suggest subchronic inflammation; detecting miRNAs related to cancer and proliferation indicates a transition from renal epithelium to pathologic tissue after fluoride exposure.

Seasonal and Spatial Variability of PM2.5 Concentration, and Associated Metal(loid) Content in the Toluca Valley, Mexico.

This study provides evidence of the seasonal and spatial variation of metal(lloid)s in particulate matter minor to 2.5 microns (PM2.5) in the Toluca Valley Metropolitan Area (TVMA), the fifth largest urban center in Mexico. Four sites were sampled between 2013 and 2014, which included urban and industrial areas, in the dry-cold (November-February) and dry-hot (March-May) seasons; PM2.5 was collected using high- and medium-volume samplers. Metal(lloid) concentrations in PM2.5 were analyzed using inductively coupled plasma‒mass spectrometry (ICP‒MS). The highest 24-hour PM2.5 concentration in the northern area was observed, and the PM2.5 concentrations were independent of the season. Five metal(lloid)s with a recovery percentage above 80% were considered to be reported (Co, Cr, Cu, Mn, and Sb). The maximum concentrations of metal(lloid)s were observed during the dry-cold season, and concentrations were up to one hundred or thousand fold with respect to the dry-hot season. The 24-hour PM2.5 and metal(lloid) concentrations exceeded national and international guidelines to protect population health.

Plasma Endothelial and Oxidative Stress Biomarkers Associated with Late Mortality in Hospitalized COVID-19 Patients.

BACKGROUND: Coronavirus infectious disease 2019 (COVID-19) is a significant public health problem worldwide. COVID-19 increases the risk of non-pulmonary complications such as acute myocardial injury, renal failure, thromboembolic events, and multi-organic damage. Several studies have documented increased inflammation molecules, endothelial dysfunction biomarkers, and dysregulation of coagulation factors in COVID-19 patients. In addition, endothelium dysfunction is exacerbated by the oxidative stress (OxS) promoted by endocrine and cardiovascular molecules. Our objective was to evaluate whether endothelial and OxS biomarkers were associated with mortality in hospitalized COVID-19 patients. METHODS: A prospective cohort study was performed. Patients ≥18 years old with confirmed COVID-19 that required hospitalization were included in a prospective cohort study. Endothelium and oxidative stress biomarkers were collected between 3 and 5 days after admission. RESULTS: A total of 165 patients were evaluated; 56 patients succumbed. The median follow-up was 71 days [23-129]. Regarding endothelial dysfunction and OxS biomarkers, patients who did not survive had higher levels of nitrates (0.4564 [0.1817-0.6761] vs. 0.2817 [0.0517-0.5], p = 0.014), total nitrates (0.0507 [-0.0342-0.1809] vs. -0.0041 [-0.0887-0.0909], p = 0.016), sE-Selectin (1.095 [0.86-1.495] vs. 0.94 [0.71-1.19], p = 0.004), and malondialdehyde (MDA) (0.50 [0.26-0.72] vs. 0.36 [0.23-0.52], p = 0.010) compared to patients who survived. Endothelial and OxS biomarkers independently associated with mortality were sE-selectin (HR:2.54, CI95%; from 1.11 to 5.81, p = 0.027), nitrates (HR:4.92, CI95%; from 1.23 to 19.63, p = 0.024), and MDA (HR: 3.05, CI95%; from 1.14 to 8.15, p = 0.025). CONCLUSIONS: Endothelial dysfunction (sE-selectin and nitrates) and OxS (MDA) are independent indicators of a worse prognosis in COVID-19 patients requiring hospitalization.

Osteopontin's relationship with malnutrition and oxidative stress in adolescents. A pilot study.

Osteopontin (OPN) is a protein involved in inflammatory illnesses such as fibrosis and cancer; its overexpression in cardiovascular diseases promotes the biomineralization of blood vessels and other soft tissues. Moreover, there is an active component of oxidative stress related with those diseases. The present study relates serum OPN levels with nutritional condition and oxidative stress in a group of adolescents. Anthropometric measurements were performed, and fasting blood samples were analyzed to determine OPN concentrations, blood chemistry parameters (glucose, triglycerides, total cholesterol, urea, uric acid, and creatinine) and oxidative stress biomarkers (Paraoxonase-1, Glutathione S-Transferase, Catalase, NAD(P)H Quinone Oxidoreductase, free carbonyl groups and malondialdehyde). Adolescents were categorized according to body mass index (BMI) and metabolic syndrome (MetS) criteria. We found increased OPN serum concentrations in overweight and obese adolescents, as well as in adolescents with MetS. Rises in OPN correlated with arm circumference and biomarkers of lipid peroxidation; with regard to serum glucose there was a trend to positive correlation. Our results suggest that serum OPN is associated to nutritional status and could be considered as an early biomarker of low-grade inflammation and probably the early biomineralization of soft tissues in adolescence.

Acute kidney damage by PM2.5 exposure in a rat model.

PM2.5 exposure is associated with a glomerular filtration rate (GFR) reduction, and renal tissue damage. The goal of this study was demonstrate the acute effect of PM2.5 on the kidney. Male rats were acutely exposed to PM2.5 or filtered air. Blood pressure was mesure and early kidney biomarkers were evaluated in serum and urine samples, and also IL-1ß, IL-6 and TNFα were determined. Oxidative biomarkers, angiotensin/bradykinin-related proteins, KIM-1, IL-6 and histology were determined. Blood pressure, GFR, and early kidney damage biomarkers increase together with oxidative biomarkers and angiotensin/bradykinin endocrine-related proteins increased after exposure to PM2.5. Urinary IL-6 increased after exposure to PM2.5, whereas in kidney cortex decreased. Histological changes were observed and accompanied by the induction of KIM-1. Acute exposure to PM2.5 not decline kidney function. However, it can induce early kidney damage biomarkers, oxidative stress, inflammation and angiotensin mediators, which perhabs culminates in a lose of renal function.

Effect of in vivo exposure to ambient fine particles (PM2.5) on the density of dopamine D2-like receptors and dopamine-induced [35S]-GTPγS binding in rat prefrontal cortex and striatum membranes.

Male Sprague-Dawley rats (8-9 weeks-old) were exposed for three days (acute exposure) or eight weeks (subchronic exposure) to purified air or concentrated ambient fine particles, PM2.5 (≤2.5 µm; 15 to 18-fold of ambient air; 370-445 µg/m3). In membranes from rat prefrontal cortex (PFC) or striatum, the density and function of dopamine D2-like receptors (D2Rs) were assessed by [3H]-spiperone binding and dopamine-stimulated [35S]-GTPγS binding, respectively. Glial activation was evaluated by immunoperoxidase labeling of the glial fibrillary acidic protein (GFAP). In the PFC, no significant changes in D2R density or signaling were observed after the acute and subchronic exposure to PM2.5. In the striatum, acute exposure to PM2.5 decreased D2R density, with no effect on signaling efficacy, whereas subchronic exposure did not affect D2R density but reduced signaling efficacy. Both acute and subchronic exposure to PM2.5 induced reactive gliosis in the striatum but not in the PFC. These results indicate that exposure to PM2.5 induces astrocyte activation and alters striatal dopaminergic transmission.

Acute and subchronic exposure to air particulate matter induces expression of angiotensin and bradykinin-related genes in the lungs and heart: Angiotensin-II type-I receptor as a molecular target of particulate matter exposure.

BACKGROUND: Particulate matter (PM) adverse effects on health include lung and heart damage. The renin-angiotensin-aldosterone (RAAS) and kallikrein-kinin (KKS) endocrine systems are involved in the pathophysiology of cardiovascular diseases and have been found to impact lung diseases. The aim of the present study was to evaluate whether PM exposure regulates elements of RAAS and KKS. METHODS: Sprague-Dawley rats were acutely (3 days) and subchronically (8 weeks) exposed to coarse (CP), fine (FP) or ultrafine (UFP) particulates using a particulate concentrator, and a control group exposed to filtered air (FA). We evaluated the mRNA of the RAAS components At1, At2r and Ace, and of the KKS components B1r, B2r and Klk-1 by RT-PCR in the lungs and heart. The ACE and AT1R protein were evaluated by Western blot, as were HO-1 and γGCSc as indicators of the antioxidant response and IL-6 levels as an inflammation marker. We performed a binding assay to determinate AT1R density in the lung, also the subcellular AT1R distribution in the lungs was evaluated. Finally, we performed a histological analysis of intramyocardial coronary arteries and the expression of markers of heart gene reprogramming (Acta1 and Col3a1). RESULTS: The PM fractions induced the expression of RAAS and KKS elements in the lungs and heart in a time-dependent manner. CP exposure induced Ace mRNA expression and regulated its protein in the lungs. Acute and subchronic exposure to FP and UFP induced the expression of At1r in the lungs and heart. All PM fractions increased the AT1R protein in a size-dependent manner in the lungs and heart after subchronic exposure. The AT1R lung protein showed a time-dependent change in subcellular distribution. In addition, the presence of AT1R in the heart was accompanied by a decrease in HO-1, which was concomitant with the induction of Acta1 and Col3a1 and the increment of IL-6. Moreover, exposure to all PM fractions increased coronary artery wall thickness. CONCLUSION: We demonstrate that exposure to PM induces the expression of RAAS and KKS elements, including AT1R, which was the main target in the lungs and the heart.