Subacute Exposure Research Articles

Evaluation of Hematotoxicity in Female Wistar Rats Following Sub-Acute Inhalation Exposure to Polyethylene Microplastic

Polyethylene (PE) becomes a source of microplastics that can be widely distributed through the digestive and respiratory systems. However, its effects on blood cells are still being investigated. This study aims to analyze the impact of Polyethylene Microplastic (PE-MPs) exposure on the blood of female rats, including erythrocytes, leukocytes, and platelets. This study used female Wistar rats, which were divided into control and PE-MP groups. PE-MP was administered via whole-body inhalation at a concentration of 15 mg/m³ for 4 hours daily for 28 days. The absorption of plastic particles detected in the human bloodstream is likely to occur through mucosal contact (either through ingestion or inhalation). After the exposure period, the rats were euthanized to collect blood samples through the heart. A complete blood count was performed using an automatic hematology analyzer, and blood morphology was analyzed using thin blood smears. This study used the Mann-Whitney test. PE-MP exposure increased erythrocyte and platelet counts without a corresponding rise in leukocytes. Erythrocytes showed abnormal morphology (12.73% with ovalocytes and tear-shaped cells). Erythrocyte indices (MCV, MCH, MCHC) showed no significant differences. Platelet count rose by 1.7% (p-value= 0.017). Leukocyte and neutrophil counts were lower (0.84 and 0.94 times lower, respectively), while lymphocytes and monocytes were higher (1.03 and 1.61 times higher, respectively) in the PE-MP group compared to controls. The neutrophil-to-lymphocyte ratio did not differ significantly. PE-MP exposure in rats disrupts blood parameters, altering erythrocyte morphology and increasing platelet counts. Potential causes include oxidative stress, immune responses, and compensatory mechanisms. Study limitations include a small sample size and exclusive focus on inhalation exposure. Integrating multiple exposure routes (inhalation, ingestion, dermal) could offer a broader view of microplastic impacts. Future research with larger samples, diverse doses and durations, and exploration of additional markers or organ-specific effects is crucial for understanding PE-MP toxicity in real-world scenarios.

Subacute tributyltin exposure alters the development and morphology of mammary glands in association with CYP19A1 expression in female rats

Tributyltin (TBT) is an endocrine-disrupting chemical (EDC) related to reproductive dysfunctions. However, few studies have investigated the effects of TBT exposure on mammary gland development. Thus, we assessed whether subacute TBT exposure causes irregularities in mammary gland development. We administered TBT (100 and 1,000 ng/kg/day for 30 days) to female rats from postnatal day (PND) 25 to PND 55, and mammary gland development, morphology, inflammation, collagen deposition, and protein expression were evaluated. Abnormal mammary gland development was observed in both TBT groups. Specifically, TBT exposure reduced the number of terminal end buds (TEBs), type 1 (AB1) alveolar buds, and type 2 (AB2) alveolar buds. An increase in the lobule and differentiation (DF) 2 score was found in the mammary glands of TBT rats. TBT exposure increased mammary gland blood vessels, mast cell numbers, and collagen deposition. Additionally, both TBT rats exhibited intraductal hyperplasia and TEB-like structures. An increase in estrogen receptor alpha (ERα), progesterone receptor (PR), and cytochrome P450 family 19 subfamily A member 1 (CYP19A1) - positive cells was observed in the mammary glands of TBT rats. A strong negative correlation was observed between CYP19A1- positive cells and TEB number. In addition, CYP19A1 - positive cells were positively correlated with mammary gland TEB-like structure, ductal hyperplasia, inflammation, and collagen deposition. Thus, these data suggest that TBT exposure impairs mammary gland development through the modulation of CYP19A1 signaling pathways in female rats.

Arsenite-Induced Drug-Drug Interactions in Rats.

Arsenite is an important heavy metal. Some Chinese traditional medicines contain significant amounts of arsenite. The aim of this study was to investigate subacute exposure of arsenite on activities of cytochrome P450 enzymes and pharmacokinetic behaviors of drugs in rats. Midazolam, tolbutamide, metoprolol, omeprazole, caffeine, and chlorzoxazone, the probe substrates for cytochrome P450 (CYP) s3A, 2C6, 2D, 2C11, 1A, and 2E, were selected as probe drugs for the pharmacokinetic study. Significant decreases in areas under the curves of probe substrates were observed in rats after consecutive 30-day exposure to As at 12 mg/kg. Microsomal incubation study showed that the subacute exposure to arsenite resulted in little change in effects on the activities of P450 enzymes examined. However, everted gut sac study demonstrated that such exposure induced significant decreases in intestinal absorption of these drugs by both passive diffusion and carrier-mediated transport. In addition, in vivo study showed that the arsenite exposure decreased the rate of peristaltic propulsion. The decreases in intestinal permeability of the probe drugs and peristaltic propulsion rate most likely resulted in the observed decreases in the internal exposure of the probe drugs. Exposure to arsenite may lead to the reduction of the efficiencies of pharmaceutical agents coadministered resulting from the observed drug-drug interactions. SIGNIFICANCE STATEMENT: Exposure to arsenite may lead to the reduction of the efficiencies of pharmaceutical agents coadministered resulting from the observed drug-drug interactions. The present study, we found that P450 enzyme probe drug exposure was reduced in arsenic-exposed animals (areas under the curve) and the intestinal absorption of the drug was reduced in the animals. Subacute arsenic exposure tends to cause damage to intestinal function, which leads to reduced drug absorption.

Impact of Cadmium Chloride (CdCl2) Exposure on Glucose Levels in Various Tissues of Heteropneustes fossilis

The present study examines the implications of acute and sub-acute exposure to cadmium chloride (CdCl2) on tissue specific glucose metabolism in muscle, gill, liver, heart, and kidney, after 30 and 60 days. Data represent significant increase in tissue glucose levels, corresponding to the metabolic response caused by cadmium-induced stress. We found out the glucose level after that 24 hour in the liver where the liver had the highest glucose levels, that the liver was going through its detox phase. Our results support a model in which there are systemic metabolic adaptations to cadmium toxicity having broader implications for how the metabolic response to exposure of an environmental toxicant is seen.

Subacute exposure to DEHP leads to impaired decidual reaction and exacerbates the risk of early miscarriage in mice.

To investigate the effect of subacute exposure of Di (2-ethylhexyl) phthalate (DEHP) on endometrial decidualization and early pregnancy miscarriage in mice. CD1 mice were orally administrated with 300 (low-dose group), 1000 (medium-dose group), or 3000 mg·kg－1·d－1 DEHP (1/10 LD50, high-dose group) for 28 days, respectively. An early natural pregnancy model and an artificially induced decidualization model were established. The uterine tissues were collected on D7 of natural pregnancy and D8 of artificially induced decidualization, respectively. The effects of a subacute exposure to DEHP on the decidualization of mice were detected by HE staining, Masson staining, TUNEL assay, and Western blotting. A model of spontaneous abortion was constructed in mice after subacute exposure to 300 mg·kg－1·d－1 DEHP, and the effect of impaired decidualization on pregnancy was investigated by observing the pregnancy outcome on the 10th day of gestation. Compared with the control group, the conception rate was significantly decreased in the high-dose DEHP subacute exposure group (P<0.05). HE staining showed that, compared with the control group, the decidual stromal cells in the low- and medium-dose exposure groups were disorganized, the nuclei of the cells were irregular, the cytoplasmic staining was uneven, and the number of polymorphonuclear cells was significantly reduced. Masson staining showed that compared with the control group, the collagen fibers in the decidua region of the DEHP low-dose group and the medium-dose group were more distributed, more abundant and more disorderly. TUNEL assay showed increased apoptosis in the decidua area compared to the control group. Western blotting showed that the expression of BMP2, a marker molecule for endometrial decidualization, was significantly reduced (P<0.05 or P<0.01). The abortion rate and embryo resorption rate were increased, and the number of embryos, uterine wet weight, uterine area and placenta wet weight were decreased in DEHP low-dose group compared to the control group stimulated by mifepristone, an abortifacient drug (P<0.05 or P<0.01). Subacute exposure to DEHP leads to impaired endometrial decidualization during early pregnancy and exacerbates the risk of adverse pregnancy outcomes in mice.

Thyroid under siege: Unravelling the toxic impact of real-life metal mixture exposures in Wistar rats

This study explored the effect of a toxic metal(oid) mixture (cadmium, lead, arsenic, mercury, chromium, and nickel) on thyroid function in Wistar rats exposed for 28 or 90 days. Dose levels were determined based on prior human-biomonitoring investigation. The experiment included control (male/female rats, 28 and 90 days) and treated groups, reflecting the lower confidence limit of the Benchmark Dose (BMDL) for hormone levels (M1/F1, 28 and 90 days), median concentrations (M2/F2, 28 and 90 days), 95th percentile concentrations (M3/F3, 28 and 90 days) measured in a human study, and reference values for individual metals extracted from the literature (M4/F4, 28 days only). Blood and thyroid gland samples were collected at the experimental termination. Serum TSH, fT3, fT4, T3, and T4 levels were measured, and SPINA-GT and SPINA-GD parameters were calculated. In silico analysis, employing the Comparative Toxicogenomic Database and ToppGene Suite portal, aimed to reveal molecular mechanisms underlying the observed effects. Results showed greater sensitivity in the female rats, with significant effects observed at lower doses. Subacute exposure increased TSH, fT3, and T3 levels in females, while subchronic exposure in males decreased TSH and fT3 levels and increased fT4. Subacute exposure induced changes even at allegedly safe doses, emphasizing potential health risks. Histological abnormalities were observed in all the treated groups. In silico findings suggested that toxic metal exposure contributes to thyroid disorders via oxidative stress, disruption of micronutrients, interference with hormone synthesis, and gene expression dysregulation. These results indicate that seemingly safe doses in single-substance research can adversely affect thyroid structure and function when administered as a mixture. These findings highlight the complex impact of toxic metal exposure on thyroid health, emphasizing that adhering to accepted safety limits for single-substance research fails to account for adverse effects on thyroid structure and function upon exposures to metal mixtures.

Sub-acute exposure of male guppies (Poecilia reticulata) to environmentally relevant concentrations of PFOA and GenX induces significant changes in the testis transcriptome and reproductive traits

Poly- and perfluoroalkyl substances (PFAS) are frequently detected in the environment and are linked to adverse reproductive health outcomes in humans. Although legacy PFAS have been phased out due to their toxicity, alternative PFAS are increasingly used despite the fact that information on their toxic effects on reproductive traits is particularly scarce. Here, we exposed male guppies (Poecilia reticulata) for a short period (21 days) to an environmentally realistic concentration (1 ppb) of PFOA, a legacy PFAS, and its replacement compound, GenX, to assess their impact on reproductive traits and gene expression. Exposure to PFAS did not impair survival but instead caused sublethal effects. Overall, PFAS exposure caused changes in male sexual behaviour and had detrimental effects on sperm motility. Sublethal variations were also seen at the transcriptional level, with the modulation of genes involved in immune regulation, spermatogenesis, and oxidative stress. We also observed bioaccumulation of PFAS, which was higher for PFOA than for GenX. Our results offer a comprehensive comparison of these two PFAS and shed light on the toxicity of a newly emerging alternative to legacy PFAS. It is therefore evident that even at low concentrations and with short exposure, PFAS can have subtle yet significant effects on behaviour, fertility, and immunity. These findings underscore the potential ramifications of pollution under natural conditions and their impact on fish populations.

Toxic effect and mRNA mechanism of moon dust simulant induced pulmonary inflammation in rats

Moon dust presents a significant hazard to manned moon exploration missions, yet our understanding of its toxicity remains limited. The objective of this study is to investigate the pattern and mechanism of lung inflammation induced by subacute exposure to moon dust simulants (MDS) in rats. SD rats were exposed to MDS and silica dioxide through oral and nasal inhalation for 6 hours per day continuously for 15 days. Pathological analysis indicated that the toxicity of MDS was lower than that of silica dioxide. MDS led to a notable recruitment and infiltration of macrophages in the rat lungs. Material characterization and biochemical analysis revealed that SiO2, Fe2O3, and TiO2 could be crucial sources of MDS toxicity. The study revealed that MDS-induced oxidative stress response can lead to pulmonary inflammation, which potentially may progress to lung fibrosis. Transcriptome sequencing revealed that MDS suppresses the PI3K-AKT signaling pathway, triggers the Tnfr2 non-classical NF-kB pathway and IL-17 signaling pathway, ultimately causing lung inflammation and activating predominantly antioxidant immune responses. Moreover, the study identified the involvement of upregulated genes IL1b, csf2, and Sod2 in regulating immune responses in rat lungs, making them potential key targets for preventing pulmonary toxicity related to moon dust exposure. These findings are expected to aid in safeguarding astronauts against the hazardous effects of moon dust and offer fresh insights into the implications and mechanisms of moon dust toxicity.

Sub-acute oral exposure to lowest observed adverse effect level of nivalenol exacerbates atopic dermatitis in mice via direct activation of mitogen-activated protein kinase signal in antigen-presenting cells.

This study investigated the immunotoxic effects of the mycotoxin nivalenol (NIV) using antigen-presenting cells and a mouse model of atopic dermatitis (AD). In vitro experiments were conducted using a mouse macrophage cell line (RAW 264.7) and mouse dendritic cell line (DC 2.4). After cells were exposed to NIV (0.19-5µmol) for 24h, the production of pro-inflammatory cytokines (IL-1β, IL-6, and TNFα) was quantified. To further investigate the inflammatory cytokine production pathway, the possible involvement of mitogen-activated protein kinase (MAPK) pathways, such as ERK1/2, p-38, and JNK, in NIV exposure was analyzed using MAPK inhibitors and phosphorylation analyses. In addition, the pro-inflammatory effects of oral exposure to NIV at low concentrations (1 or 5ppm) were evaluated in an NC/Nga mouse model of hapten-induced AD. In vitro experiments demonstrated that exposure to NIV significantly enhanced the production of TNFα. In addition, it also directly induced the phosphorylation of MAPK, indicated by the inhibition of TNFα production following pretreatment with MAPK inhibitors. Oral exposure to NIV significantly exacerbated the symptoms of AD, including a significant increase in helper T cells and IgE-produced B cells in auricular lymph nodes and secretion of pro-inflammatory cytokines, such as IL-4, IL-5, and IL-13, compared with the vehicle control group. Our findings indicate that exposure to NIV directly enhanced the phosphorylation of ERK1/2, p-38, and JNK, resulting in a significant increase in TNFα production in antigen-presenting cells, which is closely related to the development of atopic dermatitis.

Subacute exposure to black phosphorus quantum dots induces cardiac fibrosis and the potential role of gut microbiota

Black phosphorus quantum dots (BPQDs) have been used as the nano-carrier in the field of biomedicine due to their excellent electronic conductivity, optical and thermoelectric properties. However, it is still lack of evaluation of the safety of BPQDs, specifically on the effects and mechanisms of BPQDs on heart. In this study, the specific pathogen-free male mice were orally administered with different doses of BPQDs (0.02, 0.1, 0.5 mg/kg) for 28 days. BPQDs exposure decreased the heart-body ratio and caused cardiac hypertrophy and fibrosis. Additionally, ferroptosis was observed in the cardiac tissue. The recent study has shown BPQDs oral exposure alter gut microbiota. Here, after exposure to 0.1 mg/kg BPQDs for 28 days, the germ-free mice showed neither cardiac injury nor ferroptosis. Taken together, the study demonstrates that BPQDs induce cardiac ferroptosis and fibrosis, possibly mediated by gut microbiota. This research may aid in enhancing understanding of the biosafety of BP nanomaterials and promoting the sustainable development of nanotechnology.

Dose-dependent alteration in hepatic and cerebral glucose metabolism following exposure to polystyrene microplastic in Wistar rats

Background: Recently, microplastics (MPs) with dimensions less than 5 mm have gained more attention due to their adverse impact on the environment and living creatures. Polystyrene (PS) particle is a key element of primary microplastics, which are causing numerous health issues such as interruption of energy metabolism, oxidative stress, neurotoxicity, immunotoxicity, digestive gland disorders, reproductive disruption, and genotoxicity in marine living organisms. Method: Alteration in carbohydrate metabolism was evaluated in male Wistar rats (six weeks of age) after four weeks of oral exposure to polystyrene microplastic (PS-MP) at three different doses (0.5mg/L, 5mg/L and 50 mg/L via drinking water). Results: Polystyrene exposure caused a significant decrease in blood glucose, liver glycogen, and pyruvic acid content in liver and cerebral tissue. Free amino nitrogen content significantly altered in the liver and cerebrum in a dose-specific manner. The LDH activity was found to be decreased in the liver, whereas it increased in the cerebral cortex of rats in a dose-responsive fashion. Enzymes like glucose 6-phosphatase, GOT, GPT, and succinate dehydrogenase activities demonstrated differential effects on the liver and cerebrum of rats in terms of energy metabolism. Conclusion: It is suggested that sub-acute polystyrene exposure significantly perturbs glucose metabolism by inducing hypoglycemia associated with decreased glycolysis and increased TCA cycle enzyme function in rat liver in a dose-dependent manner. Gluconeogenesis is also affected differentially by metabolic adjustment in the studied organs.

Impact of sub-acute exposure to nuvan on serum lipoproteins of catfish, Clarias batrachus and their potential effects indirectly on human health

Pesticides are frequently applied in agricultural land, public health programs, and maintenance of trees or plants and also used as preservatives for different food materials for a long time. But these pesticides cause a lot of negative health and environmental impacts which affects the sustainability of an ecosystem. Among the different pesticides organophosphorus pesticide mostly used in agricultural purposes to prevent the disease causing agents like insects, pests, parasite due to its less persistence in our environment. Synthetic pesticide like Nuvan accumulations in the tissues of animals produce cyto-toxicity and have severed health issues due to its persistent nature. When these pesticides intake by aquatic animals specially fishes, they can interfere with the food chain. When such contaminated fishes eaten by someone they can destroy multiple systems in the body of human and other livings. Changes in blood biochemical indices gives signs what is happening in body of animals after exposure of pesticides. Most edible and commercially valuable freshwater fish Clarias batrachus was used in this work for analyzed the hazardous nature of toxic pesticide nuvan on some biochemical parameters. When fish exposed to two sub-lethal levels of nuvan (0.0137 ml/L and 0.0274 ml/L) for 60 days showed that the pesticide induces changes in blood parameters. The results showed very highly significant (p&lt;0.001) increase in Low- density lipoprotein-cholesterol (LDL) and highly significant (p&lt;0.01) increase in Very low- density lipoprotein-cholesterol (VLDL) while very highly significant (p&lt;0.001) reduction in high density lipoprotein- cholesterol (HDL) were noted in treated groups compared with the control. This study implicates that adverse effect on lipoproteins due to synthetic pesticides have a negative health effect as cardiovascular risk status. Research of environmental pollution and its adverse effects on human and other animals including fish is remarkable which can leads the sustainability of our environment.

Germ-free status but not subacute polychlorinated biphenyl (PCB) exposure altered hepatic phosphatidylcholine and ether-phosphatidylcholine levels in mice

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that pose a current ecosystem and human health concern. PCB exposure impacts the gut microbiome in animal models, suggesting a mechanistic link between PCB exposure and adverse health outcomes. The presence and absence of the microbiome and exposure to PCBs independently affect the lipid composition in the liver, which in turn affects the PCB disposition in target tissues, such as the liver. Here, we investigated microbiome × subacute PCB effects on the hepatic lipid composition of conventional and germ-free female mice exposed to 0, 6, or 30 mg/kg body weight of an environmental PCB mixture in sterile corn oil once daily for 3 consecutive days. Hepatic triacylglyceride and polar lipid levels were quantified using mass spectrometric methods following the subacute PCB exposure. The lipidomic analysis revealed no PCB effect on the hepatic levels. No microbiome effect was observed on levels of triacylglyceride and most polar lipid classes. The total hepatic levels of phosphatidylcholine (PC) and ether-phosphatidylcholine (ePC) lipids were lower in germ-free mice than the conventional mice from the same exposure group. Moreover, levels of several unsaturated PCs, such as PC(36:5) and PC(42:10), and ePCs, such as ePC(36:2) and ePC(4:2), were lower in germ-free than conventional female mice. Based on a KEGG pathway meta-analysis of RNA sequencing data, the ether lipid metabolism pathway is altered in the germ-free mouse liver. In contrast to the liver, extractable lipid levels, determined gravimetrically, differed in several tissues from naïve conventional vs. germ-free mice. Overall, microbiome × subacute PCB exposure effects on hepatic lipid composition are unlikely to affect PCB distribution into the mouse liver. Further studies are needed to assess how the different extractable lipid levels in other tissues alter PCB distribution in conventional vs. germ-free mice.

Subacute Exposure to Gaseous Pollutants from Diesel Engine Exhaust Attenuates Capsaicin-Induced Cardio-Pulmonary Reflex Responses Involving Oxidant Stress Mechanisms in Adult Wistar Rats.

Intravenous injection of capsaicin produces vagal-mediated protective cardio-pulmonary (CP) reflexes manifesting as tachypnea, bradycardia, and triphasic blood pressure (BP) response in anesthetized rats. Particulate matter from diesel engine exhaust has been reported to attenuate these reflexes. However, the effects of gaseous constituents of diesel exhaust are not known. Therefore, the present study was designed to investigate the effects of gaseous pollutants in diesel exhaust, on capsaicin-induced CP reflexes in rat model. Adult male rats were randomly assigned to three groups: Non-exposed (NE) group, filtered diesel exhaust-exposed (FDE) group and N-acetyl cysteine (NAC)-treated FDE group. FDE group of rats (n = 6) were exposed to filtered diesel exhaust for 5 h a day for 5days (D1-D5), and were taken for dissection on day 6 (D6), while NE group of rats (n = 6) remained unexposed. On D6, rats were anesthetized, following which jugular vein was cannulated for injection of chemicals, and femoral artery was cannulated to record the BP. Lead II electrocardiogram and respiratory movements were also recorded. Results show that intravenous injection of capsaicin (0.1ml; 10µg/kg) produced immediate tachypneic, hyperventilatory, hypotensive, and bradycardiac responses in both NE and FDE groups of rats. However, these capsaicin-induced CP responses were significantly attenuated in FDE group as compared to the NE group of rats. Further, FDE-induced attenuation of capsaicin-evoked CP responses were diminished in the N-acetyl cysteine-treated FDE rats. These findings demonstrate that oxidant stress mechanisms could possibly be involved in inhibition of CP reflexes by gaseous pollutants in diesel engine exhaust.

Altered metabolome and microbiome associated with compromised intestinal barrier induced hepatic lipid metabolic disorder in mice after subacute and subchronic ozone exposure

Exposure to ozone has been associated with metabolic disorders in humans, but the underlying mechanism remains unclear. In this study, the role of the gut-liver axis and the potential mechanism behind the metabolic disorder were investigated by histological examination, microbiome and metabolome approaches in mice during the subacute (4-week) and subchronic (12-week) exposure to 0.5 ppm and 2.5 ppm ozone. Ozone exposure resulted in slowed weight gain and reduced hepatic lipid contents in a dose-dependent manner. After exposure to ozone, the number of intestinal goblet cells decreased, while the number of tuft cells increased. Tight junction protein zonula occludens-1 (ZO-1) was significantly downregulated, and the apoptosis of epithelial cells increased with compensatory proliferation, indicating a compromised chemical and physical layer of the intestinal barrier. The hepatic and cecal metabolic profiles were altered, primarily related to lipid metabolism and oxidative stress. The abundance of Muribaculaceae increased dose-dependently in both colon and cecum, and was associated with the decrease of metabolites such as bile acids, betaine, and L-carnitine, which subsequently disrupted the intestinal barrier and lipid metabolism. Overall, this study found that subacute and subchronic exposure to ozone induced metabolic disorder via disturbing the gut-liver axis, especially the intestinal barrier. These findings provide new mechanistic understanding of the health risks associated with environmental ozone exposure and other oxidative stressors.

Inhalation exposure to polystyrene nanoplastics induces chronic obstructive pulmonary disease-like lung injury in mice through multi-dimensional assessment

Nanoplastics are widely distributed in indoor and outdoor air and can be easily inhaled into human lungs. However, limited studies have investigated the impact of nanoplastics on inhalation toxicities, especially on the initiation and progression of chronic obstructive pulmonary disease (COPD). To fill the gap, the present study used oronasal aspiration to develop mice models. Mice were exposed to polystyrene nanoplastics (PS-NPs) at three concentrations, as well as the corresponding controls, for acute, subacute, and subchronic exposure. As a result, PS-NPs could accumulate in exposed mice lungs and influence lung organ coefficient. Besides, PS-NPs induced local and systemic oxidative stress, inflammation, and protease-antiprotease imbalance, resulting in decreased respiratory function and COPD-like lesions. Meanwhile, PS-NPs could trigger the subcellular mechanism to promote COPD development by causing mitochondrial dysfunctions and endoplasmic reticulum (ER) stress. Mechanistically, ferroptosis played an important role in the COPD-like lung injury induced by PS-NPs. In summary, the present study comprehensively and systematically indicates that PS-NPs can damage human respiratory health and increase the risk for COPD.

The potential health risks of N,N-dimethylformamide: An updated review.

N,N-dimethylformamide (DMF) is a universally used industrial material with exponential growth in production and consumption worldwide. The frequently reported occupational DMF poisoning cases in some countries and the gradually recognized unavoidable health risks to the general population highlight that DMF should still be a matter of concern. Previous studies have demonstrated that the liver is the primary target organ of DMF exposure and multiple mechanisms have been revealed. However, most of these studies investigate the detrimental effects of acute and subacute DMF exposure, while the effects of chronic DMF exposure are rarely studied. Furthermore, the key mechanism for the acute hepatotoxicity of DMF remains to be elucidated. Future research may focus on the identification of efficient preventive measures against the toxicity of DMF to occupational workers, the investigation of the detrimental effects of DMF at environmentally relevant doses, and the studies on the elimination and recycling of DMF in industrial wastes. Herein, we present an updated review of the metabolism of DMF, the biomarker of DMF exposure, underlying molecular mechanisms of DMF-induced hepatotoxicity, and the toxicity of DMF to both occupational workers and general populations and discuss the possible directions in future studies.

The effect of repeated lipopolysaccharide endotoxin challenge on immune response of breeding ewes and subsequent lamb performance.

Infectious disease caused by exposure to Gram-negative bacterial endotoxin lipopolysaccharide (LPS) is recognized to suppress female fertility. However, the effect of varying low-dose endotoxin exposure during distinct stages of follicle development on immune response, reproductive performance, and lamb performance has yet to be elucidated. Therefore, the objective of this study was to evaluate acute phase response, mRNA abundance of inflammatory markers, reproductive performance and lamb growth characteristics of ewes challenged with subclinical doses of LPS. Rambouillet ewes (n = 36; 68.2±1.1kg; age 3 to 7 yr) stratified by body weight (BW) and age were assigned to treatment groups. Ewes received subcutaneous injections of saline (CON, n = 12), 1.5 µg/kg BW LPS (LOW, n = 12), or 3.0 µg/kg BW LPS (HIGH, n = 12) on days 5, 10, and 15 of a synchronized follicular wave. Ewes were subsequently placed with a raddle-painted ram on day 16 for a 35-d breeding season. On treatment days 5 and 15, blood samples, peripheral blood leukocytes, and rectal temperature were collected before and at regular intervals for 12h after LPS challenge. Immune response to LPS was confirmed by increased temperature and serum cortisol concentrations on days 5 and 15. Endotoxin increased circulating plasma concentration of the acute phase protein, haptoglobin by greater than 15%, in both LPS-treated groups on days 5 and 15 at 12h compared with control (P≤ 0.05). Pro- and anti-inflammatory mRNA gene expression demonstrated no differences in expression for tumor necrosis factor-α or peroxisome proliferator-activated receptor gamma among treatment groups (P > 0.10). Likewise, Toll-like receptor 4 (TLR4), interleukin-8 (IL-8), and superoxide dismutase 2 (SOD2) expression was similar among treatment groups on day 5. However, ewes challenged with LPS on day 15 displayed greater mRNA expression for TLR4 from 2 to 6h (P < 0.05), a 7-fold increase for IL-8 from 1.5 to 2.5h (P < 0.05), and 8-fold induction for SOD2 from 2 to 6h (P < 0.05) as compared with controls. First service conception rates were 90% for control ewes and 75% for both treated groups (P = 0.84). Treated ewes demonstrated a reduction in lamb birth weight compared with controls (P ≤ 0.05) and a tendency for reduction of 60-d adjusted weaning weight (P = 0.09). Data suggest that subacute endotoxin exposure aligning with key follicle and oocyte maturation events results in detrimental growth performance of the subsequent lamb.

Metabolomic analysis of the serum and urine of rats exposed to diazinon, dimethoate, and cypermethrin alone or in combination

BackgroundMultiple pesticides are often used in combination for plant protection and public health. Therefore, it is important to analyze the physiological changes induced by multiple pesticides exposure. The objective of this study was to investigate the combined toxicity of the widely-used organophosphorus and pyrethroid pesticides diazinon, dimethoate, and cypermethrin.MethodsMale Wistar rats were administrated by gavage once daily with the three pesticides individual or in combination for consecutive 28 days. The metabolic components of serum and urine samples were detected by using 1H nuclear magnetic resonance (NMR)-based metabolomics method. Histopathological examination of liver and kidneys and serum biochemical determination were also carried out.ResultsThe results showed that after the 28-day subacute exposure, serum glutamic transaminase and albumin were significantly increased and blood urea nitrogen was significantly decreased in the rats exposed to the mixture of the pesticides compared with the control rats, suggesting that the co-exposure impaired liver and kidney function. Metabolomics analysis indicated that the indicators 14 metabolites were statistically significant altered in the rats after the exposure of the pesticides. The increase in 3-hydroxybutyric acid in urine or decrease of lactate and N-acetyl-L-cysteine in serum could be a potentially sensitive biomarker of the subchronic combined effects of the three insecticides. The reduction level of 2-oxoglutarate and creatinine in urine may be indicative of dysfunction of liver and kidneys.ConclusionIn summary, the exposure of rats to pesticides diazinon, dimethoate, and cypermethrin could cause disorder of lipid and amino acid metabolism, induction of oxidative stress, and dysfunction of liver and kidneys, which contributes to the understanding of combined toxic effects of the pesticides revealed by using the metabolomics analysis of the urine and serum profiles.

Bupropion and varenicline administration reversed depressive behavior induced by acetamiprid exposure in mice: the role of nAChRs in depression.

Acetamiprid (ACE), is a popular neonicotinoid pesticide, that has a high affinity for mammalian nicotinic acetylcholine receptors (nAChRs). Therefore, ACE might induce depressive effects by perturbing the cholinergic system in mammalian. The aim of this study was to evaluate the effects of ACE exposure on depressive-like behaviors and grip strength (GS) in mice. Also the possible role of nAChR activation in depression was assessed by varenicline, and bupropion. Male Swiss mice (27±2g) were daily exposed to ACE by gavage (0.1, 1, 5mg/kg), behavioral tests took place after 3h, 7days and 15days, the subacute ACE (0.1mg/kg) exposure was assessed after 30days. Varenicline (0.5mg/kg) or bupropion (4mg/kg) were injected intraperitoneally 30min prior exposure to (1mg/kg) ACE. The locomotor activity, forced swimming test (FST), and sucrose preference (SP) test were assessed. After a week ACE dose dependently increased the immobility time during FST, and after 15days' depressive behavior was observed equally for ACE (0.1-5mg/kg). The subacute exposure (0.1mg/kg) significantly increased the immobility time, SP also declined that revealed anhedonia. These behavioral changes showed that ACE can initiate depressive effects. The changes in locomotor activity were not significant. GS significantly reduced following a week of exposure to ACE (1-5mg/kg) that indicated neurotoxicity. These effects were antagonized by bupropion or varenicline, thus ACE effect on nAChRs was essential in initiating the depressive behavior.