Evaluation of hepatorenal impairments in Wistar rats coexposed to low-dose lead,cadmium and manganese: insights into oxidative stress mechanism

The study aims to evaluate effects of chronic low-dose coexposure to lead (Pb), cadmium (Cd) and manganese (Mn) on hepatorenal toxicity and oxidative stress. Young male Wistar rats were treated with Pb acetate (1.4?mg/kg BW), Cd chloride (0.01?mg/kg BW), Mn chloride (0.14?mg/kg BW) and their combination (Pb?+?Cd?+?Mn) by oral gavage, for 15 weeks. Liver enzymes, albumin (Alb), globulin (Glb), total protein, creatinine, urea and electrolyte concentrations were measured in the serum. Hepatic and renal malondialdehyde (MDA), glutathione peroxidase-1 (GPx1) and metallothionein-1 (MT1) concentrations were measured by enzyme immunoassay technique. Chronic exposure to the metals significantly (p?<?.05) increased serum Glb concentration and decreased Alb/Glb ratio, compared to the controls. Serum creatinine concentration significantly (p?<?.05) decreased in the Pb, Cd and Pb?+?Cd?+?Mn groups, but elevated in the Mn group. Hepatic MDAs rose significantly (p?<?.05) in the Pb group, while hepatic GPx1 activities increased significantly (p?<?.05) in the Cd, Mn and Pb?+?Cd?+?Mn groups. Hepatic and renal MT1 concentration decreased (p?<?.05) in the Mn group only. Biochemical alterations were confirmed by light microscopy of the liver and kidneys, which showed degenerative changes. It is concluded that prolonged coexposure to environmentally relevant levels of Pb, Cd and Mn impairs liver and kidney functions via the induction of oxidative stress, and it underlines the importance of studying toxicants in combination.     

Prevalence and associated demographic characteristics of exposure to multiple metals and their species in human populations: The United States NHANES, 2007–2012

Lead (Pb), cadmium (Cd), mercury (Hg), and arsenic (As) are among the top 10 pollutants of global health concern. Studies have shown that exposures to these metals produce severe adverse effects. However, the mechanisms underlying these effects, particularly joint toxicities, are poorly understood in humans. The objective of this investigation was to identify and characterize prevalent combinations of these metals and their species in the U.S. NHANES population to provide background data for future studies of potential metal interactions. Exposure was defined as urine or blood levels ≥ medians of the NHANES 2007–2012 participants ≥6 years (n = 7408). Adjusted-odds ratios (adj-OR) and 95% confidence intervals were determined for covariates (age, gender, and race/ethnicity, cotinine and body mass index). Species-specific analysis was also conducted for As and Hg including iAs (urinary arsenous acid and/or arsenic acid), met-iAs (urinary monomethylarsonic acid and/or dimethylarsinic acid), and oHg (blood methyl-mercury and/or ethyl-mercury). For combinations of As and Hg species, age- and gender-specific prevalence was determined among NHANES 2011–2012 participants (n = 2342). Data showed that approximately 49.3% of the population contained a combination of three or more metals. The most prevalent unique specific combinations were Pb/Cd/Hg/As, Pb/Cd/Hg, and Pb/Cd. Age was consistently associated with these combinations: adj-ORs ranged from 10.9 (Pb/Cd) to 11.2 (Pb/Cd/Hg/As). Race/ethnicity was significant for Pb/Cd/Hg/As. Among women of reproductive age, frequency of oHg/iAs/met-iAS and oHg/met-iAs was 22.9 and 40.3%, respectively. These findings may help prioritize efforts to assess joint toxicities and their impact on public health.     

Assessment of heavy metals by ICP-OES and their impact on insulin stimulating hormone and carbohydrate metabolizing enzymes

Arsenic (As) and cadmium (Cd) have recently emerged as major health concerns owing to their strong association with diabetes mellitus (DM). We aimed to investigate the heavy metals exposure towards incidence of DM at various enzymatic and hormonal levels. Additionally, association of As and Cd with Zinc (Zn, essential metal) was also evaluated. Spot urine samples were collected to assess As, Cd and Zn through ICP-OES. Serum was analyzed by assay method for fasting blood glucose, liver and renal function biomarkers. ELISA was performed to investigate the impact of heavy metals on HbA1c, α-amylase, DPP-IV, IGF-1, leptin, GSH, MDA, SOD, HDL, FFA, TG and interleukin (IL)-6. Association of heavy metals with DM was measured by odds ratio (OR) and level of significance was assessed by Chi-squared test. Unpaired student's t-test was used to compare DM-associated risk factors in heavy metals-exposed and unexposed participants. As and Cd were detectable in 75.4% and 83% participants with mean concentration of 75.5 ppb and 54.5 ppb, respectively. For As exposure, OR in the third quartile was maximum ie 1.34 (95% CI, 0.80 to 2.23), however the result was not statistically significant (P > .05). For Cd exposure, OR in the fourth quartile was considerably high, 1.62 (95% CI, 1.00 to 2.61), with a significant probability value (P < .05). Urinary Cd was negatively associated with Zn. As and Cd exposure increases the incidence of DM in the general population. Impaired hormonal and enzymatic levels in diabetic and non-diabetic exposed participants reflect the multiple organ damage by heavy metal exposure.     

Co-exposure to lead increases the renal response to low levels of cadmium in metallurgy workers

Purpose

Research on the effect of co-exposure to Cd and Pb on the kidney is scarce. The objective of the present study was to assess the effect of co-exposure to these metals on biomarkers of early renal effect.

Methods

Cd in blood (Cd-B), Cd in urine (Cd-U), Pb in blood (Pb-B) and urinary renal biomarkers, i.e., microalbumin (μ-Alb), beta-2-microglobulin (β₂-MG), retinol binding protein (RBP), N-acetyl-β-d-glucosaminidase (NAG), intestinal alkaline phosphatase (IAP) were measured in 122 metallurgic refinery workers examined in a cross-sectional survey.

Results and conclusions

The median Cd-B, Cd-U, Pb-B were: 0.8 μg/l (IQR = 0.5, 1.2), 0.5 μg/g creatinine (IQR = 0.3, 0.8) and 158.5 μg/l (IQR = 111.0, 219.3), respectively. The impact of Cd-B on the urinary excretion of NAG and IAP was only evident among workers with Pb-B concentrations ≥75th percentile. The association between Cd-U and the renal markers NAG and RBP was also evidenced when Pb-B ≥75th percentile. No statistically significant interaction terms were observed for the associations between Cd-B or Cd-U and the other renal markers under study (i.e., μ-Alb and β2-MG). Our findings indicate that Pb increases the impact of Cd exposure on early renal biomarkers.     

Benchmark dose estimation of urinary and blood cadmium as biomarkers of renal dysfunction among 40‐75‐year‐old non‐smoking women in rural areas of southwest China

This study evaluated the association between urinary cadmium (U‐Cd) and blood Cd (B‐Cd) and several biomarkers of renal dysfunction (α₁‐microglobulin [α₁‐MG], β₂‐microglobulin [β₂‐MG], N‐acetyl‐β‐d ‐glucosaminidase, metallothionein, retinol‐binding protein and microalbumin [mALB]) and identified the biomarker(s) that was most closely correlated with U‐Cd and B‐Cd among female residents in rural areas of southwest China. U‐Cd, creatinine (Cr), B‐Cd and the above‐mentioned six biomarkers in morning spot urine samples were measured from 288 randomly selected 40‐75‐year‐old non‐smoking women from non‐polluted areas and Cd‐polluted‐areas. The lower 95% confidence limit of the benchmark dose (BMD) corresponding to the 5% (BMDL₀₅) and 10% benchmark response (BMDL₁₀) was calculated with assumed cut‐off values of the 95th and 90th percentile. Among the investigated women, a significant positive association was found among mALB, β₂‐MG and U‐Cd as well as B‐Cd. By using the cut‐off value of the 95th percentile, the BMDL₀₅/BMDL₁₀ of U‐Cd and B‐Cd were 4.33/8.89 μg/g Cr for mALB and 1.35/2.77 μg/L for β₂‐MG, respectively. The BMDL₀₅/BMDL₁₀ of U‐Cd (B‐Cd) was 2.73/5.60 μg/g Cr (1.00/2.05 μg/L) for mALB, if the cut‐off value was set at the 90th percentile. Therefore, β₂‐MG and mALB in urine were good biomarkers for long‐term environmental Cd exposure assessment among the six biomarkers studied for the study pool in southwest China. Our findings may help us to understand the association between nephrotoxicity and Cd exposure, and aid in the decision‐making of authorities for environmental Cd pollution and public health.     

Effects of selected heavy metals (Pb, Cu, Ni, and Cd) in the aquatic medium on the restoration potential and accumulation in the stem cuttings of the terrestrial plant, Talinum triangulare Linn

The heavy metal (Cu, Pb, Ni, and Cd) accumulation capacity of the stem cuttings of the terrestrial, ornamental plant, Talinum triangulare was assessed in hydroponic medium. The stem cuttings of T. triangulare, grew well in distilled water regenerating roots and aerial parts. On exposure to various concentrations of Cu, Pb, Ni, and Cd, a concentration dependent decrease was observed in the number of leaves produced and roots regenerated and an increase in the number of days required for the initiation of roots. The number of leaves produced showed an increasing trend in almost all treatment concentrations of Cu, Pb, Ni, and Cd with an increase in the duration of experiment, whereas, with an increase in the treatment concentration of metals a significant (P < 0.05) decrease was observed in the number of leaves produced. The number of days required for root initiation in metal solutions, however, increased with increasing concentration of Cu, Pb, Ni, and Cd. The root development was completely arrested from 10 mg l⁻¹ of Ni and 4 mg l⁻¹ of Cd. Compared to the control, a significant decrease was recorded in the number of roots produced in all treatment concentrations of Cu, Pb, Ni, and Cd. Pink colouration of metal solution consequent to leaching of plant pigment from T. triangulare was observed which was not persistent and disappeared after a few days. Decaying of stem was observed when exposed to Ni and Cd but not to Cu and Pb. Although, copper accumulation by T. triangulare at treatment concentration of 15 and 20 mg l⁻¹ exceeded 1,000 mg kg⁻¹ dry matter, necessary pot culture experiment is required before “T. triangulare” can be definitely classified as a Cu hyperaccumulator.     

The physiological response and sub-cellular localization of lead and cadmium in Iris pseudacorus L.

The seedling development and physiological responses of Iris pseudacorus L. to Pb and Cd and their combination were studied for 28 days liquid culture and sub-cellular localization of Pb and Cd in the root tip cells treated with 2,070 mg L⁻¹ Pb and 1,000 mg L⁻¹Cd for 16 days sand culture was evaluated. Results showed that the dry weights (DWs) of shoots and roots of I. pseudacorus were significantly decreased at 500 mg L⁻¹Pb and 25 mg L⁻¹Cd + 500 mg L⁻¹Pb treatments and the root DWs under all treatments were significantly decreased in comparison with that of control. The concentrations of Chla in the leaves were decreased at all treatments, while, the concentrations of Chlb and total carotenoids were not significantly decreased under 25 mg L⁻¹Cd and 25 mg L⁻¹Cd + 500 mg L⁻¹Pb treatments. The MDA and proline concentrations and POD activities in the shoots and roots were increased under treatments of 500 mg L⁻¹Pb and 25 mg L⁻¹Cd + 500 mg L⁻¹Pb, but POD activities in the shoots and roots and MDA concentrations in the shoots were significantly decreased at 25 mg L⁻¹ Cd treatment. The results of sub-cellular localization of Pb and Cd showed that numerous Pb deposits were found on the inner surface of died cell walls in the cortex treated with 2,070 mg L⁻¹ Pb and Cd deposits were found in the cell wall treated with 1,000 mg L⁻¹ Cd. Pb and Cd deposits were not found in the cytoplasm. The results indicated that POD and proline showed strong beneficial properties against Pb and Cd stress and there were some mechanisms keeping most cells with normal activities in the plant from Pb toxicity by sacrificing a few cells that accumulated a large amount Pb. Sub-cellular localizations of Pb and Cd in the root tip cells of I. pseudacorus were little difference with the localizations in other species of Iris in the previous studies.     

The association between active/passive smoking and toxic metals among pregnant women in Greece

1. Exposure to toxic metals during pregnancy may have detrimental effects on foetal development. We assessed the role of sociodemographic characteristics and active and passive smoking on blood concentrations of metals (As, Cd, Pb, Hg, Sb, U, Mn and Mo).

2. Venous blood drawn from 50 pregnant women, randomly selected from the mother–child birth cohort ‘Rhea’. Extensive questionnaire data on active and passive smoking were collected. Urinary cotinine was measured to validate self-reported exposure and non-smoking status.

3. Smokers had higher concentrations of Cd (1.0 µg/L) as compared with non-smokers (0.29 µg/L, P?<?0.001) and a tendency for higher As and Hg. Among non-smokers, blood As and Hg concentrations were also associated with exposure to passive smoking in public venues and the family home and to overall greater secondhand smoke (SHS) exposure (As: 0.97µg/L among heavy-exposed compared with 0.20 µg/L among the low-exposed, P?<?0.05; Hg: 2.1 µg/L vs. 0.9 µg/L respectively, P?<?0.05). Controlling for fish and seafood intake altered the statistical significance but not the direction of the above associations.

4. Smoking was associated with higher Cd concentrations in pregnant women, although the association between passive smoking and elevated As and Hg concentrations was indicative, however inconclusive.

     

Changes in urinary PGE<Subscript>2</Subscript> after ibuprofen treatment in preterm infants with patent ductus arteriosus

Purpose  To investigate changes in urinary PGE₂ after ibuprofen treatment in preterm infants with patent ductus arteriosus (PDA). Methods  Twenty preterm infants with a hemodynamically significant PDA (gestational age, 28.6 ± 2.3 weeks) and 20 controls (gestational age, 30.4 ± 1.5 weeks) were prospectively enrolled at 48–72 h of life. After enrollment, the former underwent conventional ibuprofen-lysine treatment. At 48–72 h (T₀) and 108–144 h of life (T₁), urine samples were noninvasively collected in both groups to measure urinary PGE₂ concentrations (enzyme immunoassay method), and renal function was investigated. Results  Urinary PGE₂ decreased significantly both in ibuprofen-treated patients (66.95 ± 16.78 vs. 27.15 ± 17.92 pg/mL, P < 0.001) and in controls (71.7 ± 16.2 vs. 53.2 ± 18.4 pg/mL, P < 0.001) from T₀ to T₁. However, urinary PGE₂ at T₁ was significantly lower (P < 0.001) in the ibuprofen group compared to the control group. Acute renal failure occurred in three ibuprofen-treated patients (15%). Conclusions  Ibuprofen markedly reduces (59.4%) urinary PGE₂ and may alter renal function in the newborn.     

Acute toxicity measured in the amphipod Ampelisca brevicornis after exposure to contaminated sediments from Spanish littoral

Sediment toxicity of different areas of Spanish littoral was evaluated using an internationally recommended 10 day acute toxicity test with the amphipod Ampelisca brevicornis. Sediment samples from Santander Bay (N Spain), Las Palmas of Gran Canaria (SW Spain), Algeciras Bay (S Spain) and Ría of Huelva (SW Spain) were collected and organic carbon, fines, metals Zn, Cd, Pb, Cu, Ni, Co and Hg, PAHs and PCBs were analyzed for their characterization. Significant toxic effects compared with control site (P < 0.05) were observed after exposure to the sediments from Las Palmas of Gran Canaria port, from 83.3% of the sites studied in Algeciras Bay and from Ría of Huelva. These effects were associated (P < 0.05) with PCBs and metals Zn, Cd, Pb and Cu in Ría of Huelva and to Ni and Co in the rest of sites. Chemical measurements were compared with international sediment quality guidelines and site-specific guidelines were derived.     

Determination of pharmacokinetic parameters of vitamin K1 in rats after an intravenous infusion

Pharmacokinetic parameters of vitamin K1 have a large range of values in different literature. The aim of this study was to determine the pharmacokinetic parameters of vitamin K1 following post-constant speed intravenous infusion (PCSII) to provide rational pharmacokinetic parameters of vitamin K1 and compare these with results of noncompartmental analysis following intravenous injection (IV). After 15 hours intravenous infusion of vitamin K1 in rats, the logarithmic concentration–time curve of vitamin K1 was fit to a linear equation following PCSII (R² = 0.9599 ± 0.0096). Then, half-time (T_1/2), apparent volume of distribution (V_d), and clearance rate (CL) were estimated successively. T_1/2 of vitamin K1 was 4.07 ± 0.41 hour, CL was 89.47 ± 3.60 mL/h, and V_d was 525.38 ± 54.45 mL in rats following PCSII. There was no significant difference in pharmacokinetic parameters of vitamin K1 among different sampling times. For noncompartmental analysis, T_1/2 and mean residence time (MRT_INF) for a sampling duration of 6h were shorter than those of 12 hours or 24 hours sampling duration following IV (P < .05, P < .01). In addition, T_1/2 of vitamin K1 was obviously different from MRT-equated half-time (T_{1/2, MRT})(P < .05). V_d and CL of vitamin K1 following PCSII were larger than those following IV based on noncompartmental analysis (P < .01). The results demonstrated that drug distribution in the body was balanced and the Napierian logarithmic concentration–time curve of vitamin K1 fit to a linear equation following PCSII. Vitamin K1 has a long T_1/2 and a relatively large V_d following PCSII.     

Evaluation of urinary cadmium and lead as markers of background exposure of middle-aged women in Korea: dietary intake as an influential factor.

The study was conducted to examine the validity of urinary cadmium (Cd) and lead (Pb) in comparison with the metals in blood as a biological marker of non-occupational exposure of general populations. Participants in four survey sites in Korea (107 non-smoking Korean women aged 30-49 years) offered peripheral blood, morning spot urine, and 24-h total food duplicate samples. Analysis of Cd and Pb was accomplished by graphite furnace atomic absorption spectrophotometry. The analyse levels were evaluated on an individual basis (n = 107) and also on a survey site basis, i.e. in terms of geometric means for the groups in the survey sites (n = 4). Cd in urine (as observed, or after correction for creatinine concentration or a specific gravity) correlated with Cd in blood on an individual as well as survey site basis, and tended to correlate with Cd in food duplicates on the survey site basis. Correlation of Pb in urine with Pb in blood was weaker than that of Cd in urine with Cd in blood both on the individual and survey site basis. Pb in urine correlated with Pb in food duplicates either weakly or even negatively when examined on a survey site basis. It was concluded that Cd in urine can be most probably employed as a biological marker of environmental Cd exposure of general population, whereas less support was obtained for Pb in urine as an exposure marker.     

Role of mechanistic target of rapamycin (mTOR) in renal function and ischaemia–reperfusion induced kidney injury

Despite the presence of many studies on the role of mechanistic target of rapamycin (mTOR) in cardiorenal tissues, the definitive role of mTOR in the pathogenesis of renal injury subsequent to ischaemia–reperfusion (IR) remains unclear. The aims of the current study were to characterize the role of mTOR in normal kidney function and to investigate the role of mTOR activation in IR‐induced kidney injury. In euvolemic anaesthetized rats, treatment with the mTOR inhibitor rapamycin increased blood pressure (121 ± 2 to 144 ± 3 mmHg; P<.05), decreased glomerular filtration rate (GFR; 1.6 ± 0.3 to 0.5 ± 0.2 mL/min; P<.05) and increased urinary sodium excretion (UNaV; 14 ± 1 to 109 ± 25 mmol/L per hour; P<.05). In rats subjected to IR, autophagy induction, p‐mTOR expression and serum creatinine increased (1.9 ± 0.2 to 3 ± 0.3 mg/dL; P<.05); treatment with rapamycin blunted p‐mTOR expression but further increased autophagy induction and serum creatinine (3 ± 0.3 to 5 ± 0.6 mg/dL; P<.05). In contrast, clenbuterol, an mTOR activator, blunted the effect of rapamycin on serum creatinine (4 ± 0.6 vs 2.3 ± 0.3 mg/dL; P<.05), autophagy induction and p‐mTOR expression. IR also increased 24 hour protein excretion (9 ± 3 to 17 ± 2 mg/day; P<.05) and kidney injury molecule‐1 (KIM‐1) expression, and rapamycin treatment further increased KIM‐1 expression. Clenbuterol exacerbated protein excretion (13 ± 2 to 26 ± 4 mg/day; P<.05) and antagonized the effect of rapamycin on KIM‐1 expression. Histopathological data demonstrated kidney injury in IR rats that was worsened by rapamycin treatment but attenuated by clenbuterol treatment. Thus, mTOR signalling is crucial for normal kidney function and protecting the kidney against IR injury through autophagy suppression.     

E-Cigarette Outcome Expectancies among Nationally Representative Samples of Adolescents and Young Adults

Objectives: We conducted nationally representative surveys of adolescents and young adults to examine associations between e-cigarette outcome expectancies and e-cigarette use. Background: E-cigarette use among adolescents and young adults has grown rapidly in recent years, yet little research has examined the beliefs that may underlie this behavior among nationally representative samples. Methods: N?=?1,298 adolescents (13–17) and 2,219 young adults (18–25) were surveyed using a probability-based web panel. Participants completed a survey that included a new outcome expectancy measure examining 3 positive (enjoyment, social influences, advantage over cigarettes) and 2 negative (health concerns, smoker association) expectancy domains and ever having used e-cigarettes [ever use]. Results: Confirmatory factor analyses demonstrated a good fit of the outcome expectancies’ factor structure to the data. All outcome expectancies were associated with e-cigarette use in both populations in univariate analyses. In multiple logistic regression models controlling for several covariates, higher expected enjoyment was positively associated with a greater likelihood of e-cigarette use (aOR = 2.10, p < .05) among adolescents. Among young adults, enjoyment (aOR = 3.08, p < .001) was positively associated with a greater likelihood of use while both health concerns (aOR = 0.70, p < .01) and smoker association (aOR = 0.73, p < .05) were negatively associated with e-cigarette use. Conclusions: This study suggests that expected enjoyment is robustly associated with e-cigarette use among both adolescents and young adults. Health concerns may also play a role in e-cigarette use. Implications for e-cigarette prevention efforts and future research directions are discussed.     

Heavy metal (Pb,Cu, Zn,and Cd) concentrations in the water and muscle of common carp (Cyprinus carpio) fish and associated non-carcinogenic risk assessment: Alagol wetland in the Golestan,Iran

Short- and long-term exposure to heavy metals can be dangerous for human health. One of the main routes of exposure to heavy metals is intake of seafood such as fish. In this study, lead (Pb), copper (Cu), zinc (Zn), and cadmium (Cd) concentration in the water and muscle of C. Carpio fish was measured and non-carcinogenic risk of these heavy metals was estimated. The mean (range) concentrations of Cu, Zn, Pb, and Cd were 7.92?±?7.99 (1.22–39.43?mg/kg), 120.90?±?106.25 (1.15–477?mg/kg), 5.84?±?5.22 (ND-21.86?mg/kg), and 0.027?±?0.043 (ND-0.14). Except Cd, the concentrations of Cu, Zn, and Pb were significantly more than Food and Agricultural Organization United Nations (FAOUN) maximum guidelines (p??Cu?>?Pb?>?Cd in the water and muscle tissue of C. carpio fish. Lowest and highest target hazard quotient (THQ) for adults was related to Cd (0.005) and Pb (0.252) and for children, Cd (0.003) and Pb (0.168), respectively. The rank order of THQ for adults and children are Pb?>?Zn?>?Cu?>?Cd. Since THQ and hazard index (HI) for both adults and children were significantly lower than 1 (p?C. Carpio fish consumption.     

The Relationship between Blood and Serum Lead Levels in Peripartum Women and their Respective Umbilical Cords

Abstract: Foetal exposure to lead (Pb) during pregnancy is a major problem. However, no previous study has examined whether Pb concentrations in blood (Pb‐B) and in serum (Pb‐S) from pregnant women correlate with Pb‐B and Pb‐S in the foetuses. This hypothesis was tested in the present study. We measured Pb‐B and Pb‐S in 120 healthy pregnant women (more than 38 weeks of gestation) and their respective umbilical cord samples. The analyses were carried out with an inductively coupled plasma mass spectrometer. We found higher Pb‐B levels in the women compared with their respective umbilical cord samples (1.736 ± 0.090 μg/dL and 1.194 ± 0.062 μg/dL, respectively; p < 0.05). In parallel, we found higher Pb‐S levels in the women compared with their respective umbilical cord samples (0.042 ± 0.003 μg/dL and 0.032 ± 0.003 μg/dL, respectively; p < 0.05). However, similar %Pb‐S/Pb‐B ratios were found in the women compared with their respective umbilical cord samples (2.414 ± 0.210% and 2.740 ± 0.219%, respectively; p > 0.05). Interestingly, we found positive correlations between Pb‐B in the umbilical cords and Pb‐B in the respective pregnant women (rs = 0.5714; p < 0.0001), and between Pb‐S in the umbilical cords and Pb‐S in the respective pregnant women (rs = 0.3902; p < 0.0001) as well as between %Pb‐B/Pb‐S in the umbilical cords and %Pb‐B/Pb‐S in the respective pregnant women (rs = 0.3767; p < 0.0001). These results indicate that the assessment of Pb‐B and Pb‐S in pregnant women provides relevant indexes of foetal exposure to Pb. Moreover, the similar %Pb‐S/Pb‐B in pregnant women and in the umbilical cords shows that the foetuses are directly exposed to the rapidly exchangeable Pb fraction found in their mothers.     

Alterations of valve closing behavior in juvenile Catarina scallops (Argopecten ventricosus Sowerby, 1842) exposed to toxic metals

We conducted an evaluation of alterations produced in the valve closing speed of juvenile Argopecten ventricosus (Catarina scallop) exposed to the metals cadmium, chromium and lead, because of the connection of this response to the state of health of the mollusk. Bioassays were conducted with 50 juveniles (length 3 ± 0.5 cm) exposed to 0.02, 0.1, 0.2 mg Cd l⁻¹; 0.1, 0.5, 1.0 mg Cr l⁻¹; 0.04, 0.2, 0.4 mg Pb l⁻¹ and 0.8 and 1.6 mg Cd + Cr + Pb l⁻¹ for 480 h. The average valve closing speed at the end of the experiment was under 1 s in the control group, from 2 to 3.6 s in the bioassays with cadmium, from 1.4 to 3.4 s with chromium, from 3 to 12 s with lead, and from 12 to 15 s with the metal mixtures. It was found that there are significant differences between the values recorded in assays with metals and the control (P < 0.05). The retardation of valve closing in the organisms exposed to toxic substances is probably caused by damage to the sensory cilia located on the edge of the mantle.     

Prorenin receptor mediates inflammation in renal ischemia

We hypothesized that PRR contributes to renal inflammation in the 2‐kidney, 1‐clip (2K1C) renal ischaemia model. Male Sprague‐Dawley rats were fed normal sodium diet. Blood pressure (BP) was obtained on days 0 and 28 after left renal artery clipping that reduced renal blood flow by 40%. Renal expression of TNF‐α, COX‐2, NF‐κB, IL‐1β, MCP‐1 and collagen type I were assessed in sham and 2K1C rats with or without left renal administration of scramble or PRR shRNA. At baseline, there were no differences in BP. Compared to sham, MAP significantly increased in clipped animals (sham 102 ± 1.9 vs 2K1C 131.8 ± 3.09 mmHg, P < .05) and was not influenced by scramble or PRR shRNA treatment. Compared to sham and contra lateral (non‐clipped) kidney, there was upregulation in mRNA and protein expression of PRR (99% and 45%, P < .01), TNF‐α (72% and 50%, P < .05), COX‐2 (72% and 39%, P < .05), p‐NF‐κB (92%, P < .05), MCP‐1 (87%, P < .05) and immunostaining of collagen type I in the clipped kidney. These increases were not influenced by scramble shRNA. Compared to 2K1C and scramble shRNA, PRR shRNA treatment in the clipped kidney significantly reduced the expression of PRR (62% and 57%, P < .01), TNF‐α (51% and 50%, P < .05), COX‐2 (50% and 56%, P < .05), p‐NF‐κB by 68% (P < .05), MCP‐1 by 73% (P < .05) and collagen type I respectively. Ang II was increased in both kidneys and did not change in response to scramble or PRR shRNA treatments. We conclude that PRR mediates renal inflammation in renal ischaemia independent of blood pressure and Ang II.     

Ligustrazine attenuates elevated levels of indoxyl sulfate,kidney injury molecule-1 and clusterin in rats exposed to cadmium

In this study, we aimed at evaluating the effect of ligustrazine, a major constituent of Ligusticum wallichii from traditional Chinese medicine, on Cd-induced changes in nephrotoxicity indices. Rats were divided into four experimental groups: control; ligustrazine; Cd and ligustrazine + Cd. Cd treated alone group showed significant decreases (P < 0.05) in body weight, renal levels of superoxide dismutase (SOD) and glutathione reductase (GR); and significant increases (P < 0.05) in urine volume (24 h), pH values, serum blood urea nitrogen (BUN), serum uric acid, kidney malondialdehyde (MDA), urinary total protein, urinary glucose, urinary lactate dehydrogenase (LDH) and urinary alkaline phosphatase (ALP). Apart from indoxyl sulfate (a uremic toxin), two newly accepted nephrotoxicity biomarkers including kidney injury molecule-1 (kim-1) and clusterin were also found to be increased. Nonetheless, all these effects induced by Cd were reversed upon treatment by ligustrazine although it failed in decreasing the concentrations of Cd in kidney and urine. Histopathological studies in Cd-treated rats exhibited renal tubule damage, which was also ameliorated by ligustrazine pretreatment. These results suggest that ligustrazine exhibits protective effects on Cd-induced nephrotoxicity. Additionally, this study also demonstrates Cd exposure induces elevated levels of indoxyl sulfate in serum and kidney, and clusterin in urine.