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Background Environmental noise exposure is linked to neuroinflammation and imbalance of the gut microbiota. Promoting gut microbiota homeostasis may be a key factor in relieving the deleterious non-auditory effects of noise. This study aimed to investigate the effect of Lactobacillus rhamnosus GG (LGG) intervention on noise-induced cognitive deficits and systemic inflammation in rats. Methods Learning and memory were measured using the Morris water maze, while 16S rRNA sequencing and gas chromatography-mass spectrometry were used to analyze the gut microbiota and short-chain fatty acid (SCFA) content. Endothelial tight junction proteins and serum inflammatory mediators were assessed to explore the underlying pathological mechanisms. Results The results indicated that LGG intervention ameliorated noise-induced memory deterioration, promoted the proliferation of beneficial bacteria, inhibited harmful bacteria, improved dysregulation of SCFA-producing bacteria, and regulated SCFAs levels. Mechanistically, noise exposure led to a decrease in tight junction proteins in the gut and hippocampus and an increase in serum inflammatory mediators, which were significantly alleviated by LGG intervention. Conclusions Taken together, LGG intervention reduced gut bacterial translocation, restored gut and blood-brain barrier functions, and improved gut bacterial balance in rats exposed to chronic noise, thereby protecting against cognitive deficits and systemic inflammation by modulating the gut-brain axis.

Cerebral ischemia causes severe neurological disorders and neuronal dysfunction. Baicalin (BC), geniposide (GP), and their combination (BC/GP) have been shown to inhibit post-ischemic inflammatory injury by inhibiting the 5-LOX/CysLTs pathway. The aims of this study were to observe the inhibitory effects of BC/GP on the activation of microglial cells induced by oxygen glucose deprivation and reoxygenation (OGD/R) and to investigate whether the 5-LOX/LTB4 pathway was involved in these effects. Molecular docking showed that BC and GP exhibited considerable binding activity with LTB4 synthase LTA4H. BV-2 microglia were transfected with a 5-LOX overexpression lentiviral vector, and then OGD/R was performed. The effects of different concentrations of BC, GP, and BC/GP (6.25 μM, 12.5 μM, and 25 μM) on cell viability and apoptosis of microglia were evaluated by MTT and flow cytometry. The expression of TNF-α, IL-1β, NF-κB, and pNF-κB also was measured by ELISA, Western blots and immunofluorescence. Western blots and qRT-PCR analysis were used to determine the levels of CD11b, CD206, and 5-LOX pathway proteins. Results showed that BC, GP, and BC/GP reduced the apoptosis caused by OGD/R in a dose-dependent manner, and cell viability was significantly increased at a concentration of 12.5 μM. OGD/R significantly increased the release of TNF-α, IL-1β, NF-κB, pNF-κB, and CD11b. These effects were suppressed by BC, GP, and BC/GP, and the OGD/R-induced transfer of NF-κB p65 from the ctytoplasm to the nucleus was inhibited in microglia. Interestingly, the LTB4 inhibitor, U75302, exhibited the same effect. Also, BC, GP, and BC/GP significantly reduced the expression of 5-LOX pathway proteins. These results demonstrated that BC/GP inhibited OGD/R-induced polarization in BV2 microglia by regulating the 5-LOX/LTB4 signaling pathways and attenuating the inflammatory response. Our results supported the theoretical basis for additional in-depth study of the function of BC/GP and the value of determining its unique target, which might provide a new therapeutic strategy for ischemic cerebrovascular disease.

Manufactured zinc oxide nanoparticles (Nano-ZnO) are being used increasingly in many fields owing to their excellent physicochemical properties. Consequently, biosecurity has become a growing concern for human health and the environment. In the present study, Nano-ZnO neurotoxicity was investigated in vivo and in vitro. In vivo results showed that Nano-ZnO particles delivered through intranasal instillation were translocated to the brain, specifically deposited in the olfactory bulb, hippocampus, striatum, and cerebral cortex, and caused ultrastructural changes, oxidative damage, inflammatory responses, and histopathological damages there, which may be important for inducing Nano-ZnO neurotoxicity. Further in vitro studies on PC12 cell line illustrated that exposure to Nano-ZnO for 6 h affected cell morphology, decreased cell viability, increased lactate dehydrogenase and oxidative stress activity levels, impaired mitochondrial function, and disturbed the cell cycle. In addition, Nano-ZnO could destroy neuronal structure by affecting cytoskeleton proteins (tubulin-α, tubulin-β and NF-H), resulting in the interruption of connection between nerve cells, which lead to nervous system function damage. Meanwhile, Nano-ZnO could induce neuronal repair and regeneration disorders by affecting the growth-related protein GAP-43 and delayed neurotoxicity by affecting the calcium/calcium-regulated kinase (CAMK2A/CAMK2B protein) signaling pathway.

Previous studies demonstrated that tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) caused adverse effects on thyroid hormone (TH) imbalance in aquatic and avian organisms. This study focused on the effects of TDCIPP on thyroid function and hormone homeostasis in mammals. Pubertal female Sprague-Dawley rats were orally administered 50, 100, or 250 mg per kg per d of TDCIPP from postnatal day (PND) 22 to PND42 for 21 days. The serum triiodothyronine (T3) levels increased significantly at 250 mg per kg per d of TDCIPP. There were no significant differences in the body weight, serum thyroxine (T4) and free thyroxine (FT4) levels between the control and TDCIPP treated groups. There were significant dose-dependent increases in the mRNA and protein expression levels of genes related to drug metabolism (cytochrome-p450-3A1, CYP3A1) and TH clearance (udp-glucuronosyltransferase-1A6, UGT1A6) in the liver. Treatment with TDCIPP increased hepatic type 1 deiodinase (DIO1) mRNA at 250 mg per kg per d but down-regulated hepatic TH receptor beta (TRβ) mRNA expression. In addition, TDCIPP exposure induced slight thyroid follicular hyperplasia, and several genes involved in TH biosynthesis (NIS, TPO, Tg) were altered at 100 and 250 mg per kg per d of TDCIPP. Nevertheless, serum thyroid stimulating hormone (TSH) levels and the receptor (TSHr) mRNA significantly decreased at only the low dose group. Based on these results, we certified that TDCIPP disturbs the normal bioprocess on TH synthesis, biotransformation or clearance, and hepatic detoxification of pubertal female SD rats, causing thyroid function disorder.

The central nervous system is a potential target for Al2O3 nanoparticles (Nano-Al2O3). Here, we investigated the effects of intranasal instillation of Nano-Al2O3 on the distribution and damage in crucial functional sub-brain regions of rats. In vivo results show that Nano-Al2O3 was translocated into the brain via the olfactory nerve pathway. Nano-Al2O3 accumulated in the hippocampus, olfactory bulb, cerebral cortex, and striatum, causing ultrastructural changes, oxidative damage, inflammatory responses, and histopathological damage in sub-brain regions. As indicated by in vitro studies, cell viability decreased with the addition of Nano-Al2O3, which increased the levels of lactate dehydrogenase and oxidative stress. Nano-Al2O3 also impaired mitochondrial function, disturbed the cell cycle and induced apoptosis. In addition, Nano-Al2O3 decreased the expression of cyclin D1, bcl-2, Mdm2, and phospho-Rb and increased the expression of p53, p21, Bax, and Rb. Therefore, oxidative stress, mitochondrial dysfunction, and p53-related pathways might be important in the process of dopaminergic neurotoxicity induced by Nano-Al2O3. The current study establishes a striatum damage model and identifies molecular biomarkers of dopaminergic neuron damage induced by Nano-Al2O3. In brief, our study demonstrates that Nano-Al2O3 exposure can be a risk factor for neurodegenerative diseases and may negatively impact the hippocampus, striatum, and dopaminergic neurons.

Zinc oxide, titanium dioxide and silver nanoparticles are used as sterilization materials to enhance the performance of disinfectants. Here, the toxicological effects on the liver, spleen, thymus gland, immune function and inflammatory responses in rats induced by these nanoparticles were investigated after intratracheal instillation in male Wistar rats. Moreover, the relationships between the particle size, particle crystalline structure, chemical composition, chemical stability and toxicological effects of these typical nanoparticles in rats were explored. Exposure to nanoparticles increased the oxidative stress level in peripheral blood and the homogenates of the liver, spleen and thymus as well as disorders in regulating the cytokine network and blood cell count in the peripheral blood. Furthermore, the histopathological study revealed that pulmonary exposure to nanoparticles produced persistent, progressive liver inflammatory responses and cell necrosis, while no observable damage was found in the kidney, thymus gland or spleen tissue from the experimental groups. Our results demonstrate that oxidative stress might be important for inducing the toxic effects of these nanoparticles, and three nanoparticles can influence the immune function of rats. A comparative analysis of the toxic effects of nanomaterials demonstrated significant differences. Nano-ZnO induced the most significant toxicity, whereas nano-TiO2 induced the least. Particle composition and chemical stability probably played a primary role in the toxicological effects of different nanoparticles.

Epidemiological studies have demonstrated that nanometre particles in polluted air can increase the risk of CVD, which is dangerous to mankind. However, little is known regarding the indirect toxic effects on the cardiovascular system of respiratory tract exposure to nanometre particles. As a typical nanomaterial, SWCNTs have gained enormous popularity because of their unique properties. However, increasing attention has been paid to the potential pulmonary toxic effects of respiratory tract exposure to SWCNT than to the potential link of this exposure to cardiovascular disease risk. In this study, a rat intratracheal instillation model was used to evaluate the systemic and secondary effects of respiratory tract exposure to SWCNT, specifically changes in lung tissues, the circulatory system and vascular function. We found increased levels of inflammatory factors and interstitial inflammation in the lungs in this rat model. In addition, up-regulated levels of cytokines and an increase in white blood cells, platelets and fibrinogen were detected in the plasma. These changes were followed by increased blood viscosity in the high dose SWCNT exposure group. In addition, damage to the ultrastructure of the vascular intima in the rats was observed. Changes in coagulation and fibrinolysis activating factors were detected in the plasma. Lower expression of t-PA and higher expression of vWF were observed in the vascular intima of rats exposed to SWCNT at 10.5 and 17.5 mg per kg b.w. for 30 days and 60 days. After exposure to SWCNT for 60 days at 17.5 mg per kg b.w., decreased expression of t-PA gene and increased expression of TM, p38MAPK and PAI-1 genes were observed in the peripheral blood of the rats. Based on these results, we conclude that cardiovascular toxicity caused by respiratory tract exposure to SWCNTs may be induced by indirect effects on vascular homeostasis, which is different from previously reported direct cardiac effects of SWCNT. The present work established a correlation between pulmonary changes and CVD following pulmonary exposure to SWCNT. This study indicates a possible pathophysiological mechanism for CVD caused by pulmonary exposure to SWCNT. More importantly, these results supplement toxicological evaluation data for the risk of CVD caused by respiratory tract exposure to SWCNT.

Pentachlorophenol (PCP) and 2,4,6-trichlorophenol (TCP) are suspected of disrupting the endocrine system and thus affecting human and wildlife reproduction, but the potential common mechanisms and biomarkers of chlorophenols (CPs) in the ovary are not fully elucidated. In the present study, the female rare minnow (Gobiocypris rarus) was exposed to PCP (0.5, 5.0, and 50 μg/L), TCP (1.0, 10, and 100 μg/L) and 17β-estradiol (as a positive control) for 28 days, and the matrix-assisted laser desorption/ionization (MALDI) tandem time-of-flight (TOF/TOF) mass spectrometry analysis was employed to investigate the alteration of protein expression in the ovary. After comparison of the protein profiles from treated and control groups, 22 protein spots were observed to be altered in abundance (> 2-fold) from female treated groups, and 14 protein spots were identified successfully. These proteins were related to molecular response patterns, endocrine effects, metabolic pathways, and even the possible carcinogens in response to CP exposure. The seven differentially expressed mRNA encoding proteins were measured by quantitative real-time PCR (QRT-PCR) and histopathology was also measured. Our data demonstrate that alterations of multiple pathways may be associated with the toxic effects of CPs on ovaries. Biological significance Although numerous studies have shown the affection of the endocrine system with exposure to chlorophenols (CPs), there is little report on the alterations of protein expression in the ovaries from rare minnows following exposure to PCP or TCP. In the present study, a comparative proteomic approach using two dimensional gel electrophoresis and mass spectrometry (MALDI-TOF/TOF MS) has been developed to identify certain proteins in the ovaries of Chinese rare minnow, whose abundance changes during exposure to CPs. After comparison of the protein profiles from treated and control groups, 22 protein spots were observed to be altered in abundance (> 2-fold) from female treated groups, and 14 protein spots were identified successfully. These proteins were related to molecular response patterns, endocrine effects, metabolic pathways, and even the possible carcinogens in response to CP exposure. Because the mechanism often involves changes in the expression of multiple proteins rather than a single protein, a global analysis of the protein alterations can result in valuable information to understand the CP action mechanism. All the above results demonstrate that the Vtg, SUMO, Lec-3 and PIMT protein are potential biomarkers and involved in the toxicity pathway of CP exposure in aquatic animals, which should be the primary focus of studies on the CP ovary toxicity mechanism in the future.

Thiazole-Zn is a newly chinese-created systemic fungicide, and belongs to the sort of thiadiazole compounds, some of which have been found to be thyroid disrupters. To determine the probable adverse effects of thiazole-Zn on thyroid gland and development function, the rodent 20-day Pubertal Female Assay in this study was used. Postnatal days (PND) 22-old Sprague–Dawley rats were administered with thiazole-Zn daily by oral gavage at doses 0, 40, 100, 200 mg/kg/day for 20 days. The thyroid endpoints and development endpoints were assessed. The results indicated that serum TT4 and TSH levels were significantly increased at all concentrations, serum TT3 levels were significantly reduced only at 40 mg/kg thiazole-Zn, but had no difference from controls at the other doses. Thyroid histology was significantly altered at all doses with a clear dose-dependent hypertrophy and hyperplasia of thyroid cell. No histological changes were observed in any of the other observed organs. In addition, this study also found that ovarian weights were significantly decreased, but age and weight at vaginal opening (VO), serum E2 levels were unaffected in all treatment groups. These results demonstrate that thiazole-Zn is likely a thyroid disrupter, but did not demonstrate that it has estrogenic/anti-estrogenic activity.

Silver, zinc oxide, and titanium dioxide nanoparticles are used as sterilisation materials to enhance the performance of disinfectants. We investigated the respiratory tract immune toxicity ("immunotoxicity") of these nanoparticles in vivo and in vitro, and we explored the relationships between particle size, particle shape, chemical composition, chemical stability and the toxicological effects of these typical nanoparticles in rats. In vivo, the rats were exposed to nanoparticles by intratracheal instillation. Exposure to nanoparticles caused an increase in oxidative injury to the lungs and disorders in regulating the cytokine network, which were detected in the bronchoalveolar lavage fluid, suggesting that oxidative stress might be important for inducing the respiratory immunotoxicity of nanoparticles. In vitro, the phagocytic function of alveolar macrophages (AMs) was dose-dependently reduced by nanoparticles, and ZnO nanoparticles induced greater cytotoxicity than the silver and titanium-dioxide nanoparticles, which were coincident with the results of multiple measurements, such as a cell viability assay by WST-8 and LDH measurements. Comparative analyses demonstrated that particle composition and chemical stability most likely had a primary role in the biological effects of different nanoparticles.

Tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) is one of the widely used organophosphorus flame retardants (OPFRs), which are regarded as suitable substitutes for brominated flame retardants (BFRs). Previously, we have validated the toxicity of TDCIPP in PC12 cells owing to the induced alterations in GAP43, NF-H, CaMK2a/2b, and tubulin α/β proteins; however, limited information is currently available on the toxicity and mechanism of TDCIPP. In the present study, cytotoxicity effects were evaluated by exposing PC12 cells to different concentrations of TDCIPP (0-50 μM) for 4 days. To explore the possible mechanisms through which cytotoxicity is induced, changes in intracellular [Ca2+ ]i levels and the activation of calmodulin dependent protein kinase 2 (CaMK2), c-Jun N-terminal kinase (JNK), extracellular regulated protein kinases (ERK1/2), and p38 mitogen-activated protein kinases (MAPK) pathways were evaluated. Furthermore, PC12 cells were pretreated with CaMK2 inhibitor KN93 to investigate the relationship between TDCIPP-induced phosphorylation of CaMK2 and activation of JNK, ERK1/2, and p38 MAPK pathways. Our results indicate that TDCIPP-induced toxicity might be associated with the overload of [Ca2+ ]i levels, increased phosphorylation of CaMK2, and activation of the JNK, ERK1/2, and p38 MAPK pathways, the lattermost of which was further demonstrated to be partially elicited by the CaMK2 phosphorylation.

Thiazole-Zn is a newly created Chinese systemic fungicide that is a thiadiazole compound. The toxicity of thiazole-Zn was examined in Sprague-Dawley rats fed diets containing 0, 4, 20 and 100mg/kg thiazole-Zn for one year. Lower body weight gains were noted in both males and females of the 100mg/kg diet group. Moreover, we show that the toxicity of thiazole-Zn was low, as evidenced by the absence of toxicologically significant changes in the general condition and appearance, hematology and clinical chemistry parameters, organ weights and necropsy findings of the rats. Thyroid follicular cell hyperplasia was the only finding of potential significance. The incidence of thyroid follicular cell hyperplasia significantly increased in high-dose males (4/10) and females (3/10) at the 26-week interim examination; one follicular adenoma in the thyroid was observed in high-dose males. At 52 weeks, the incidence of thyroid follicular cell hyperplasia was significantly higher in high-dose males (4/10) and females (4/10) than in the controls. Two thyroid follicular adenomas were observed in high-dose males. Other treatment-related effects and tumors at other sites were not observed. This study suggests that thiazole-Zn is a thyroid disrupter and likely a rat thyroid carcinogen.

Oxidative stress is a major factor contributing to endothelial cell damage. Single-wall carbon nanotubes (SWCNTs) have oxidative properties; however, the oxidative effects of SWCNTs on endothelial cells are not fully understood. In the present study, we investigated the effects of oxidative stress induced by SWCNTs on rat aortic endothelial cells (RAECs). Various markers of cellular damage were assessed, such as biochemical and ES immunity indexes, and DNA and protein damage. Our findings suggest that RAEC endured oxidative damage following SWCNT exposure. Specifically, after SWCNTs exposure, non-enzymatic antioxidant glutathione was activated prior to superoxide dismutase activation in order to defend against oxidative stress. Additionally, it was found that as SWCNT concentration increased, so did the stress protein, heme oxygenase-1 (HO-1), expression levels. These changes may induce RAEC damage, and result in many serious diseases.

The toxicological effects of single-walled carbon nanotubes (SWCNTs) were investigated after intratracheal instillation in male Wistar rats over a 15-day period using metabonomic analysis of 1H (nuclear magnetic resonance) NMR spectra of blood plasma and liver tissue extracts. Concurrent liver histopathology examinations and plasma clinical chemistry analyses were also performed. Significant changes were observed in clinical chemistry features, including alkaline phosphatase, total protein, and total cholesterol, and in liver pathology, suggesting that SWCNTs clearly have hepatotoxicity in the rat. 1H NMR spectra and pattern recognition analyses from nanomaterial-treated rats showed remarkable differences in the excretion of lactate, trimethylamine oxide, bilineurin, phosphocholine, amylaceum, and glycogen. Indications of amino acid metabolism impairment were supported by increased lactate concentrations and decreased alanine concentrations in plasma. The rise in plasma and liver tissue extract concentrations of choline and phosphocholine, together with decreased lipids and lipoproteins, after SWCNTs treatment indicated a disruption of membrane fluidity caused by lipid peroxidation. Energy, amino acid, and fat metabolism appeared to be affected by SWCNTs exposure. Clinical chemistry and metabonomic approaches clearly indicated liver injury, which might have been associated with an indirect mechanism involving nanomaterial-induced oxidative stress.