Cadmium (Cd), as an environmental pollutant, can lead to nephrotoxicity. However, its nephrotoxicological mechanisms have not been fully elucidated. In this study, Cd (1.5 mg/kg body weight, gavaged for 4 weeks) was found to induce the renal damage in mice, based on indicators including Cd concentration, kidney index, serum creatinine and blood urea nitrogen levels, pro-inflammatory cytokines and their mRNA expressions, levels of Bcl-2, Bax and caspase9, and histopathological changes of the kidneys. Furthermore, Cd-caused detrimental changes through inducing inflammation and apoptosis via the miR-34a/Sirt1/p53 axis. This is the first report on the role of miR-34a/Sirt1/p53 axis in regulating Cd-caused apoptosis and nephrotoxicity in mice. The findings obtained in this study provide new insights into miRNA-based regulation of heavy metal induced-nephrotoxicity.

All European bats are protected by the EU and Associated Members legal regulations. Being insectivorous and top predators, they can be particularly exposed to persistent organic and inorganic pollutants. It is surprising how little is known about the impact of environmental pollutants on bats from physiological to populational levels. In this study we focused on contamination with trace metals of first-year bats from Kharkiv city, NE Ukraine. Tissues from the carcasses of two species, Nyctalus noctula (n = 20) and Eptesicus serotinus (n = 20), were used for metal analysis. The samples of external (wing membrane, fur) and internal (liver, lung, kidney, bones) tissues were analysed for contents of Pb, Cu, Zn, and Cd to see whether fur or wing membrane can be used as proxies for metal contamination of the vital internal tissues. In E. serotinus, significant positive correlations in Pb concentrations were found between all external and internal tissues. For Cd only, correlation between the fur and lung was found, for Cu between the fur and liver, and for Zn between the fur and kidney. In contrast, for N. noctula, only one such correlation was found – between Zn concentrations in the fur and kidney. The tissues differed significantly in concentrations of all studied metals, with no difference between the species. The results showed that the fur and wing membrane can be used as good proxies for Pb concentrations in internal organs of E. serotinus, but not necessarily for other metals or for N. noctula. The results for Pb are, however, encouraging enough to conclude that the topic is worth further studies, covering more species, a wider age range and more diverse environments.

Mercury (Hg) is an environmental contaminant that poses a threat to aquatic systems globally. Temporal evaluations of Hg contamination have increased in recent years, with studies focusing on how anthropogenic activities impact Hg bioavailability in a variety of aquatic systems. While it is common for these studies and ecological risk assessments to evaluate Hg bioaccumulation and effects in wildlife, there is a paucity of information regarding Hg dynamics in reptiles. The goal of this study was to investigate temporal patterns in total mercury (THg) and methylmercury (MeHg) concentrations across a 36-year period, as well as evaluate relationships among and between destructive (kidney, liver, muscle) and non-destructive (blood, tail) tissue types in a common watersnake species. To accomplish this, we measured THg and MeHg concentrations in multiple tissues from brown watersnakes (Nerodia taxispilota) collected from Steel Creek on the Savannah River Site (SRS; Aiken, SC, USA) from two time periods (1983–1986 and 2019). We found significant and positive relationships between tail tips and destructive tissues. In both time periods, THg concentrations varied significantly by tissue type, and destructive tissues exhibited higher but predictable THg values relative to tail tissue. Methylmercury concentrations did not differ among tissues from the 1980s but was significantly higher in muscle compared to other tissues from snakes collected in 2019. Percent MeHg of THg in N. taxispilota tissues mirrored patterns reported in other reptiles, although the range of % MeHg in liver and kidney differed between time periods. Both THg and MeHg concentrations in N. taxispilota declined significantly from the 1980s to 2019, with average values 1.6 to 4-fold lower in contemporary samples. Overall, our data add further evidence to the utility of watersnakes to monitor Hg pollution in aquatic environments and suggest attenuation of this contaminant in watersnakes in our study system.

Prothioconazole (PTC), a popular agricultural fungicide, and its main metabolite prothioconazole-desthio (PTCd) are receiving great attention due to their toxicological effects in the non-target organisms. This study investigated their dosage-dependent (1 and 5 mg/kg BW/day) toxicological effects on oxidative stress and metabolic profiles of liver and kidney tissues using male mice. PTC and PTCd significantly inhibited the growth phenotype including body weights gain, liver and kidney indices. Furthermore, these effects were deeply investigated using the biomarkers of oxidative stress, and metabolomics. Notably, these effects were dose and tissue-dependent. Specifically, the more serious impacts involving oxidative stress and metabolic disorders were observed in the high concentration treatment groups. Also, the liver tissue was more severely affected than the kidney tissue. Lastly, the change in oxidative stress biomarkers and metabolomics profile revealed that PTCd induced more severe toxic effects than the parent compound PTC. In brief, these results indicate that exposure to PTC and PTCd could cause potential health risks in mammals.

Indium tin oxide (ITO) is an important semiconductor material, because of increasing commercial products consumption and potentially exposed workers worldwide. So, urgently we need to assess and manage potential health risks of ITO. Although the Occupational Exposure Limit (OEL) has been established for ITO exposure, there is still a lack of distinguishing the risks of exposure to particles of different sizes. Therefore, obtaining toxicological data of small-sized particles will help to improve its risk assessment data. Important questions raised in quantitative risk assessments for ITO particles are whether biodistribution of ITO particles is affected by particle size and to what extent systematic adverse responses is subsequently initiated. In order to determine whether this toxicological paradigm for size is relevant in ITO toxic effect, we performed comparative studies on the toxicokinetics and sub-acute toxicity test of ITO in mice. The results indicate both sized-ITO resided in the lung tissue and slowly excreted from the mice, and the smaller size of ITO being cleared more slowly. Only a little ITO was transferred to other organs, especially with higher blood flow. Two type of ITO which deposit in the lung mainly impacts respiratory system and may injure liver or kidney. After sub-acute exposure to ITO, inflammation featured by neutrophils infiltration and fibrosis with both dose and size effects have been observed. Our findings revealed toxicokinetics and dose-dependent pulmonary toxicity in mice via oropharyngeal aspiration exposure, also replenish in vivo risk assessment of ITO. Collectively, these data indicate that under the current OEL, there are potential toxic effects after exposure to the ITO particles. The observed size-dependent biodistribution patterns and toxic effect might be important for approaching the hazard potential of small-sized ITO in an occupational environment.

As ubiquitous, persistent organic pollutants, polycyclic aromatic hydrocarbons (PAHs) have adverse impacts on human health. Phenanthrene (Phe) is one of the most abundant PAHs in the environment. However, the long-term effects of exposure to environmental level of Phe on the kidneys and the potential mechanisms are unclear. T helper (Th) cells, a subtype of CD4⁺ T cells that play a central role in the renal immune microenvironment. In this study, male mice were chronically exposed to 5, 50, and 500 ng/kg bw Phe every other day for total 210 days. Those results indicated that environmental Phe exposure caused kidney hypertrophy, injury and fibrosis in the mice. Chronic, long-term environmental level of Phe exposure did not significantly alter the innate immune response but induced adaptive immune response changes (Th1/Th2 related cytokines release), causing a type 1 immune response in the 5 ng/kg bw Phe group and a type 2 immune response in the high dose groups (50 and 500 ng/kg bw). This study provides novel insights into the roles of adaptive immune response in long-term PAH exposure-induced chronic kidney injury and fibrosis, which is beneficial for further understanding the potential health hazards of PAHs and providing new avenues for immune intervention strategies to alleviate PAHs toxicity.

Although huge interspecies differences in the response to dioxins have been acknowledged, toxic equivalency factors derived from rodent studies are often used to assess human health risk. To determine interspecies differences, we first developed a toxicokinetic model in humans by measuring dioxin concentrations in environmental and biomonitoring samples from Southern China. Significant positive correlations between dioxin concentrations in blood and age were observed for seven dioxin congeners, indicating an age-dependent elimination rate. Based on toxicokinetic models in humans, the half-lives of 15 dioxin congeners were estimated to be 1.60–28.55 years. In consideration that the highest contribution to total toxic equivalency in blood samples was by 12378-polychlorinated dibenzo-p-dioxin (P₅CDD), this study developed a physiologically based pharmacokinetic (PBPK) model of 12378-P₅CDD levels in the liver, kidney, and fat of C57/6J mice exposed to a single oral dose, and the half-life was estimated to be 26.1 days. Based on estimated half-lives in humans and mice, we determined that the interspecies difference of 12378-P₅CDD was 71, much higher than the default usually used in risk assessment. These results could reduce the uncertainty human risk assessment of 12378-P₅CDD, and our approach could be used to estimate the interspecies differences of other dioxin congeners.

Metal pollution has been associated with anthropogenic activities, such as effluents and emissions from mines. Soil could be exposure route of wild rats to metals, especially in mining areas. The aim of this study was to verify whether soil exposure under environmentally relevant circumstances results in metal accumulation and epigenetic modifications. Wistar rats were divided to three groups: 1) control without soil exposure, 2) low-metal exposure group exposed to soil containing low metal levels (Pb: 75 mg/kg; Cd: 0.4), and 3) high-metal exposure group exposed to soil (Pb: 3750; Cd: 6). After 1 year of exposure, the metal levels, Pb isotopic values, and molecular indicators were measured. Rats in the high-group showed significantly greater concentrations of Pb and Cd in tissues. Higher accumulation factors (tissue/soil) of Cd than Pb were observed in the liver, kidney, brain, and lung, while the factor of Pb was higher in the tibia. The obtained results of metal accumulation ratios (lung/liver) and stable Pb isotope ratios in the tissues indicated that the respiratory exposure would account for an important share of metal absorption into the body. Genome-wide methylation status and DNA methyltransferase (Dnmt 3a/3b) mRNA expressions in testis were higher in the high-group, suggesting that exposure to soil caused metal accumulation and epigenetic alterations in rats.