While several mechanisms may explain metal-related health effects, the exact cellular processes are not fully understood. We evaluated the association between leukocyte telomere length (LTL) and urine arsenic (ΣAs), cadmium (Cd) and tungsten (W) exposure in the Strong Heart Study (SHS, N = 1702) and in the Strong Heart Family Study (SHFS, N = 1793).Urine metal concentrations were measured using ICP-MS. Arsenic exposure was assessed as the sum of inorganic arsenic, monomethylarsonate and dimethylarsinate levels (ΣAs). LTL was measured by quantitative polymerase chain reaction.In the SHS, median levels were 1.09 for LTL, and 8.8, 1.01 and 0.11 μg/g creatinine for ΣAs, Cd, and W, respectively. In the SHFS, median levels were 1.01 for LTL, and 4.3, 0.44, and 0.10 μg/g creatinine. Among SHS participants, increased urine ΣAs, Cd, and W was associated with shorter LTL. The adjusted geometric mean ratio (95% confidence interval) of LTL per an increase equal to the difference between the percentiles 90th and 10th in metal distributions was 0.85 (0.79, 0.92) for ΣAs, 0.91 (0.84, 1.00) for Cd and 0.93 (0.88, 0.98) for W. We observed no significant associations among SHFS participants. The findings also suggest that the association between arsenic and LTL might be differential depending on the exposure levels or age.Additional research is needed to confirm the association between metal exposures and telomere length.

The effect of exposure to vinyl chloride monomer (VCM) on susceptibility to hepatotoxicity in children is unknown, although experimental studies have demonstrated a significantly increased risk of hepatocellular carcinoma in rodents exposed to VCM in early life. Epidemiological studies have revealed a high prevalence of liver fibrosis and abnormal liver function in workers exposed to high VCM levels. We aimed to assess the association among urinary thiodiglycolic acid (TDGA) level, abnormal liver function, and hepatic fibrosis in school-aged children living near a petrochemical complex. A total of 303 school-aged (6–13 years) children within 10 km nearly a petrochemical complex was recruited in central Taiwan. First-morning urine and blood samples were collected from each subject, and urinary TDGA level was analyzed through liquid chromatography–tandem mass spectrometry. Liver function was determined by serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Hepatic fibrosis was assessed using the AST to platelet ratio index (APRI) and fibrosis-4 score (FIB-4). Risk of hepatotoxicity induced by TDGA exposure was estimated using multivariate logistic regression. The median (range, subclinically abnormal %) AST and ALT levels of all subjects were 26.0 (17.0–99.0, 25.7%) and 15.0 (7.0–211.0, 5.9%) IU/L, respectively. Children in the highest urinary TDGA quartile (≥160.0 μg/g creatinine) exhibited significantly elevated median AST levels compared with those in the lowest quartiles (<35.4 μg/g creatinine, p = 0.033). After adjustment for potential confounding factors, children in the highest quartiles (Q₄) of TDGA level had significantly increased odds ratio (OR) of subclinically abnormal AST (OR = 3.86; 95% confidence interval: 1.54–9.67) compared with those in the lowest quartile. A dose-response trend (p = 0.004) was observed. Our findings support the hypothesis that elevated urinary TDGA level in children living near petrochemical complex is associated with susceptibility to hepatotoxicity.

Aluminum is a widely distributed metal that has been reported to have embryotoxicity and fetotoxicity in animal studies. However, there has been no study of the association between prenatal aluminum exposure and newborn mitochondrial DNA copy number (mtDNAcn). We aimed to investigate the effect of prenatal aluminum exposure on newborn mtDNAcn. A total of 762 mother-newborn pairs were recruited between November 2013 and March 2015 in Wuhan city, China. We measured maternal urinary aluminum concentrations at three trimesters of pregnancy. Relative mtDNAcn was measured in DNA extracted from umbilical cord blood samples. We used generalized estimating equations to assess the relationship between prenatal aluminum exposure and newborn mtDNAcn. The geometric means of creatinine corrected aluminum concentrations were 31.0 μg/g Cr (95% CI: 27.6, 34.7), 40.9 μg/g Cr (95% CI: 35.7, 46.8) and 58.4 μg/g Cr (95% CI: 51.2, 67.4) for the first, second and third trimesters, respectively. After adjustment for potential confounding factors, a doubling of maternal urinary aluminum concentrations during the second and third trimesters was related to 3.16% (95% CI: 0.88, 5.49) and 4.20% (95% CI: 1.64, 6.81) increases in newborn mtDNAcn, respectively, while the association between maternal urinary aluminum concentration during the first trimester and newborn mtDNAcn was not significant (percent difference: 0.70%, 95% CI: −2.25, 3.73). Prenatal aluminum exposure during the second and third trimesters was positively associated with newborn mtDNAcn. Further studies are essential to elucidate on the potential health consequences of newborn mtDNAcn.

Pyrazole derivatives display diverse biological and pharmacological activities. The aim of this study is to investigate the antioxidant properties of a novel pyrazolecarboxamide derivative (4-amino-N-[(4-chlorophenyl)]-3-methyl-1-phenyl-1H-thieno [2, 3-c] pyrazole-5-carboxamide) in African catfish, Clarias gariepinus, exposed to 1 mg/L PbNO₃. Fish were intramuscularly injected with pyrazole-5-carboxamidederivative according to the following groupings: Group 1 (control), Group 2 (1 mg/L lead nitrate), Group 3 (1 mg/L lead nitrate + 5 mg pyrazole derivative/kg body weight), and Group 4 (1 mg/L lead nitrate + 10 mg pyrazole derivative/kg body weight) for two weeks and four weeks. Lead nitrate (1 mg/L) caused significant elevation of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, uric acid, cholesterol, and glucose-6-phosphate dehydrogenase (G6PDH) compared to the control group after two and four weeks of exposure, while serum total lipids, alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were significantly reduced compared to the control group. Furthermore, levels of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) and total antioxidant capacity (TAC) were reduced in group 2 compared to the control group. However, in group 2, hepatic lipid peroxidation (LPO) and DNA fragmentation percentage were significantly increased compared to the control group. Histopathological changes in the liver of lead-exposed groups included marked disturbance of hepatic tissue organization, degeneration of hepatocytes, dilation of blood sinusoids and the central vein as well as necrosis. Injection of pyrazole derivative for two weeks and four weeks reversed alterations in biochemical parameters, antioxidant biomarkers, lipid peroxidation, hepatic DNA damage, and histopathological changes in liver tissue induced by 1 mg/L lead nitrate. This amelioration was higher in response to high-dose pyrazole derivative (10 mg) at the fourth week of exposure, showing concentration-and time-dependency. Overall, the sensitized derivative pyrazolecarboxamide is likely a useful tool to minimize the effects of lead toxicity due to its potent antioxidant activity.

Exposure to polycyclic aromatic hydrocarbons (PAHs) during pregnancy may pose adverse health risk to both the mothers and babies. In the present study, 188 pregnant women of different trimesters were recruited in Guangzhou, south China, and nine hydroxyl PAHs (OH-PAHs) and a biomarker of DNA oxidative damage, 8-hydroxy-2′-deoxyguanosine (8-OHdG), were determined in their urine samples. All OH-PAHs except for 4-hydroxyphenanthrene and 6-hydroxychrysene were found in > 90% samples, with total concentration in the range of 0.52 to 42.9 μg/g creatinine. In general, concentration levels of OH-PAHs in pregnant women were lower than those in general population in the same research area but with higher levels in working women than in housewives. The mean daily intakes of PAHs from dietary estimated by urinary OH-PAHs were 0.021, 0.004, 0.047, and 0.030 μg/kg_bw/day for naphthalene, fluorene, phenanthrene, and pyrene, respectively, which were much lower than the reference doses (20, 30, and 40 μg/kg_bw/day for naphthalene, pyrene, and fluorene, respectively) derived from chronic oral exposure data by the United States Environmental Protection Agency. The low exposure levels of PAHs may be attributed to the traditional dietary taboo of Chinese pregnant women, which is to minimize the consumption of “toxic” food. The concentrations of 8-OHdG (4.67–49.4 μg/g creatinine) were significantly positively correlated with concentrations of several OH-PAHs, such as metabolites of naphthalene, fluorene, and phenanthrene (r = 0.3–0.6). In addition, the concentrations of 8-OHdG were higher in working women than in housewives when exposed to the same levels of PAHs, partly indicating the possible relation between work-related pressure for working women and the oxidative stress.

Epoxiconazole (EPX) is a triazole fungicide commonly used in agriculture and for domestic purposes around the world. The excessive application of this pesticide may result in a variety of adverse effects on non-target organisms, including humans. Since, the liver and kidneys are the target organs of this fungicide, potential hepatotoxic and nephrotoxic effects are of high relevance. Thus, our study aimed to investigate the toxic effects of EPX on the liver and kidney of Wistar rats. The exposure of rats to EPX at these concentrations (8, 24, 40, 56 mg/kg bw representing, respectively, NOEL (no observed effect level), NOEL × 3, NOEL × 5, and NOEL × 7) for 28 days significantly enhances hepatic and renal lipid peroxidation which is accompanied by an increase in the level of protein oxidation. Furthermore, the results of the present study clearly indicated that EPX administration induces an increase in the levels of DNA damage in a dose-dependent manner. In addition, the activities of liver and kidney antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione S-transferase (GST) are increased significantly in EPX-treated rats at concentrations of 8, 24, and 40 mg/kg bw. However, with the dose NOEL × 7 (56 mg/kg bw of EPX), the activities of CAT, GPx, and GST are decreased. Indeed, EPX-intoxicated rats revealed a significant reduction in acetylcholinesterase (AChE) activity in both liver and kidney compared with the control group. Also, our results demonstrated that the EPX administration leads to a disruption of the hepatic (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH)) and renal (uric acid and creatinine) functions. The biochemical perturbations obtained in the present study are corroborated with the histopathological modifications. Since EPX treatment caused severe damage in the overall histo-architecture of liver and kidney tissues, these results suggest that administration of EPX induced a marked deregulation of liver and kidney functions. Graphical abstract

Nanomaterial applications are a fast-developing field. In spite of their powerful advantages, many open questions regarding how these small-sized chemicals may influence the environment and human health. However, scarce reports are available on the potential hazards of combined nanoparticles, taken into consideration that nickel oxide (NiO) and cobalt (II, III) oxide (Co₃O₄) nanoparticles (NPs) are already used together in many applications. Hence, the present work was designed to study the probable changes in some biological, hematological, and serum biochemical variables throughout 2 weeks following an oral administration of 0.5 g and 1.0 g of NiO-NPs or/and Co₃O₄-NPs per kilogram body weight of rats. As compared with the controls, the exposure to NiO-NPs or Co₃O₄-NPs solely caused significant elevations in the relative weights of brain (RBW), kidney (RKW) and liver (RLW), water consumption (WC), red blood cells (RBCs) count, hemoglobin (Hb) content, packed cell volume (PCV), and serum levels of low-density lipoprotein cholesterol (LDL-C), glucose, creatinine, urea, and uric acid as well as serum activities of aspartate and alanine aminotransferases (ASAT and ALAT). In addition, remarkable declines in the total body weight (TBW), feed consumption (FC), white blood cells (WBCs) count, serum levels of total protein (TP), albumin, albumin/globulin ratio, total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) were caused by administration of NiO-NPs or Co₃O₄-NPs, separately. On contrary, the co-administration of NiO-NPs and Co₃O₄-NPs together caused less noticeable changes in most of studied variables as compared with those administered NiO-NPs or Co₃O₄-NPs, individually. In conclusion, the exposure to a combination of NiO-NPs and Co₃O₄-NPs suppressed the adverse effects of the individual NPs on the studied variables.

An unsafe level of manganese (Mn) was detected in the drinking water in some arsenic (As)-contaminated areas in Bangladesh. Mn is an essential trace element; however, the intake of a higher level of Mn through the drinking water is associated with the development of toxicity in humans. This study was designed to evaluate the effects of As and Mn co-exposure on neurobehavioral and biochemical alterations in a mouse model. Sodium arsenite (10 mg/kg body weight) and manganese chloride tetrahydrate (10 mg/kg body weight) were given to mice individually and in combination with drinking water for 90 days. Results showed that individual As and Mn exposure as well as co-exposure of As and Mn significantly (p < 0.05) reduced the percent of time spent in the open arms when compared with that of control mice. In addition, percent of time spent in open arms significantly (p < 0.05) increased in co-exposed mice compared with As exposure in elevated plus maze (42.05 ± 1.10 versus 38.94 ± 0.66). In the Morris water maze test, the mean time latency to find the platform was longer in metal-treated mice in comparison to that of control mice (p < 0.05). Importantly, the co-exposed group had shorter time when compared with the As-exposed group during the training periods (p < 0.05). Moreover, co-exposed mice stayed significantly (p < 0.05) more time in the target quadrant in the probe trial in comparison with that of As-exposed mice (27.25 ± 1.21 versus 23.83 ± 0.87 s) but less time than control mice (27.25 ± 1.21 versus 43.17 ± 1.49 s). In addition, a significant (p < 0.05) alteration of biochemical parameters such as ALT, AST, ALP, BChE, and SOD as well as urea and creatinine levels were noted in the As-exposed group compared with the control group and Mn significantly (p < 0.05) attenuated the effects of As in co-exposed mice. Therefore, the results of this study suggest that As and Mn may have some antagonistic effect and Mn could attenuate the As-induced neurobehavioral and biochemical alterations in co-exposed mice.

Colouring agents are highly present in diverse products in the human environment. We aimed to elucidate the fibrogenic cascade triggered by the food dyes tartrazine and chlorophyll. Rats were orally given distilled water, tenfold of the acceptable daily intake of tartrazine, or chlorophyll for 90 consecutive days. Tartrazine-treated rats displayed a significant rise (p < 0.05) in the mRNA levels and immunohistochemical localization of the renal and hepatic fibrotic markers collagen 1-α, TGFβ-1, and fibronectin and the apoptotic marker caspase-3. Moreover, a significant increment (p < 0.05) in the levels of AST, ALP, creatinine, and urea was evident in both experimental groups but more significant differences were noticed in the tartrazine group. Furthermore, we found a marked increment in the MDA level and significant declines (p < 0.05) in the levels of the SOD, CAT, and GSH enzymes in the kidney and liver from tartrazine-treated rats. The histological investigation reinforced the aforementioned data, revealing hepatocytes with fibrous connective tissue proliferation, apoptotic hepatocytes and periportal fibrosis with tubular necrosis, and shrunken glomeruli and interstitial fibrous tissue proliferation. We concluded that, even at the exposure to high concentrations for long durations, chlorophyll exhibited a lower propensity to induce fibrosis, apoptosis, and histopathological perturbations than tartrazine.

Aflatoxins (AFs) are mycotoxins produced by Aspergillus parasiticus and Aspergillus flavus which frequently contaminate maize. These compounds are considered toxic, especially AFB₁ which has been classified as a human carcinogen, due to its relationship with the generation of hepatocellular carcinoma. Studies in vivo, in animal models, prove that chronic consumption of AFB₁ has an association with renal adverse effects, but evidence in humans is scarce. Therefore, the main objective of this research was to conduct a pilot study to evaluate the correlation between exposure to AFB₁ and early-stage renal damage in indigenous women of San Luis Potosí, Mexico. Exposure to AFB₁ was measured through the biomarker AFB₁-lysine and renal damage through kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and cystatin-C (Cys-C). AFB₁-Lys was measured by HPLC-FLD. The method was validated with a correlation coefficient of 0.99 and limit of detection and quantification of 3.5 and 4.7 pg mL⁻¹, respectively. Levels of NGAL, KIM-1, and Cys-C were determined (median (P25–P75), 5.96 (3.16–15.91), 0.137 (0.137–0.281), and 18.49 (5.76–29.57) ng mL⁻¹, respectively). Additionally, glomerular filtration rate (GFR) (83.3 (59.8–107.4) mL/min/1.73 m²) and serum creatinine (SCr) (0.88 (0.72–1.22) mg dL⁻¹) were obtained. The median concentrations for AFB₁-Lys were 2.08 (1.89–5.8) pg mg⁻¹ of albumin. Statistically significant correlations between AFB₁-Lys/KIM-1 (Rho = 0.498, p = 0.007) and AFB₁/Cys-C (Rho = 0.431, p = 0.014) were found. Our results indicate that women are exposed to AFB₁, due to the fact that the AFB₁-Lys biomarker was found in a high percentage of the study population (83%). In addition, the results of exposure to AFB₁ show a strong significant correlation between KIM-1 and Cys-C that may indicate the toxic renal effect. These results are alarming because of the high toxicity of this compound and require adequate intervention to reduce AFB₁ exposure in these populations.