Due to intense industrialization and urbanization, air pollution has become a serious global concern as a hazard to human health. Epidemiological studies found that exposure to atmospheric ...particulate matter (PM) causes severe health problems in human and significant damage to the physiological systems. In recent days, PM exposure could be related as a carrier for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus transmission and Coronavirus disease 2019 (COVID-19) infection. Hence, it is important to understand the adverse effects of PM in human health. This review aims to provide insights on the detrimental effects of PM in various human health problems including respiratory, circulatory, nervous, and immune system along with their possible toxicity mechanisms. Overall, this review highlights the potential relationship of PM with several life-limiting human diseases and their significance for better management strategies.
•Air pollution has become global public health concern.•Particulate matter is strongly associated with SARS-CoV-2 transmission.•Particulate matter causes multiple organ damage in human.•Oxidative stress and inflammatory responses are the major cause for damage.•Health effects and molecular toxicity mechanism of organ damage was reviewed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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•The smaller sizes of three ZnO nanomaterials showed slightly higher toxicity.•Exposure to l-ZnO NRs induced developmental neurotoxicity in zebrafish larvae.•Neurotoxic hallmarks of ...l-ZnO NRs are consistent with PD-like symptoms.•Increasing the dose of l-ZnO NRs aggravated its developmental neurotoxicity to PD.
With the increasing applications in various fields, the release and accumulation of zinc oxide (ZnO) nanomaterials ultimately lead to unexpected consequences to environment and human health. Therefore, toxicity comparison among ZnO nanomaterials with different shape/size and their adverse effects need better characterization. Here, we utilized zebrafish larvae and human neuroblastoma cells SH-SY5Y to compare the toxic effects of ZnO nanoparticles (ZnO NPs), short ZnO nanorods (s-ZnO NRs), and long ZnO NRs (l-ZnO NRs). We found their developmental- and neuro-toxicity levels were similar, where the smaller sizes showed slightly higher toxicity than the larger sizes. The developmental neurotoxicity of l-ZnO NRs (0.1, 1, 10, 50, and 100 μg/mL) was further investigated since they had the lowest toxicity. Our results indicated that l-ZnO NRs induced developmental neurotoxicity with hallmarks linked to Parkinson’s disease (PD)-like symptoms at relatively high doses, including the disruption of locomotor activity as well as neurodevelopmental and PD responsive genes expression, and the induction of dopaminergic neuronal loss and apoptosis in zebrafish brain. l-ZnO NRs activated reactive oxygen species production, whose excessive accumulation triggered mitochondrial damage and mitochondrial apoptosis, eventually leading to PD-like symptoms. Collectively, the developmental- and neuro-toxicity of ZnO nanomaterials was identified, in which l-ZnO NRs harbors a remarkably potential risk for the onset and development of PD at relatively high doses, stressing the discretion of safe range in view of nano-ZnO exposure to ecosystem and human beings.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Epileptic seizures are characterized by synchronized discharges of neurons, leading to the activation of inflammatory responses that in turn contributes to seizure progression. Berberine (BBR), a ...bioactive constituent extracted from berberis, has been known to relieve seizures in rodent models. In this study, we synthesized two derivatives of berberine (BBR-D1 and BBR-D2) to compare their seizure reducing effect with BBR in pentylenetetrazole (PTZ)-induced seizures in zebrafish. We found a structure-activity relationship between hydrophilic/hydrophobic composition of the derivatives and their anticonvulsant activity. We also investigated the underlying mechanism related to their anti-inflammatory effect during seizures. BBR and its derivatives increased the seizure onset latency and suppressed the seizure-like behavior after PTZ treatment. Zebrafish larvae pretreated with BBR and its derivatives showed recovery on c-fos expression and neuronal discharges during seizures. The inflammatory responses occurred during the progression of seizures, including the recruitment of macrophages and neutrophils as well as an up-regulation of tumor necrosis factor alpha (TNFα), interleukin 1 beta (il1β), and interleukin 6 (il6). This effect was significantly suppressed by the pretreatment of BBR and its derivatives. Our results suggest that BBR and its derivatives attenuate PTZ-induced seizures and modulate anti-inflammatory effect to potentially protect zebrafish from the occurrence of further seizures. From the tested compounds, BBR-D1 (the hydrophilic berberrubine) showed the strongest seizure reducing effect.
Graphical Abstract
Two derivatives of berberine (BBR-D1 and BBR-D2) were synthesized to compare their seizure reducing effect with BBR in pentylenetetrazole (PTZ)-induced seizures in zebrafish. BBR and its derivatives increased the seizure onset latency and suppressed the seizure-like behavior after PTZ treatment. Zebrafish larvae pretreated with BBR and its derivatives showed recovery on c-fos expression and neuronal discharges during seizures. The inflammatory responses occurred during the progression of seizures, including the recruitment of macrophages and neutrophils as well as an up-regulation of tumor necrosis factor alpha (TNFα), interleukin 1 beta (il1β), and interleukin 6 (il6). This effect was significantly suppressed by the pretreatment of BBR and its derivatives.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The bark of Cinnamomum cassia (C. cassia) has been used for the management of coronary heart disease (CHD) and diabetes mellitus. C. cassia may target the vasculature, as it stimulates angiogenesis, ...promotes blood circulation and wound healing. However, the active components and working mechanisms of C. cassia are not fully elucidated. The Shexiang Baoxin pill (SBP), which consists of seven medicinal materials, including C. cassia etc., is widely used as a traditional Chinese patent medicine for the treatment of CHD. Here, 22 single effective components of SBP were evaluated against the human umbilical vein endothelial cells (HUVECs). We demonstrated that in HUVECs, cinnamaldehyde (CA) stimulated proliferation, migration, and tube formation. CA also activated the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways. Furthermore, the secretion of vascular endothelial growth factor (VEGF) from HUVECs was increased by CA. In vivo, CA partially restored intersegmental vessels in zebrafish pretreated with PTK787, which is a selective inhibitor for vascular endothelial growth factor receptor (VEGFR). CA also showed pro-angiogenic efficacy in the Matrigel plug assay. Additionally, CA attenuated wound sizes in a cutaneous wound model, and elevated VEGF protein and CD31-positive vascular density at the margin of these wounds. These results illustrate that CA accelerates wound healing by inducing angiogenesis in the wound area. The potential mechanism involves activation of the PI3K/AKT and MAPK signaling pathways. Such a small non-peptide molecule may have clinical applications for promoting therapeutic angiogenesis in chronic diabetic wounds and myocardial infarction.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
: Polyphyllin VII (PP7), a steroidal saponin from
, has been found to exert strong anticancer activity. Little is known about the anti-inflammatory property of PP7. In this study, the ...anti-inflammatory activity and its underlying mechanisms of PP7 were evaluated in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and in multiple animal models.
: The content of nitric oxide (NO) was determined by spectrophotometry. The levels of prostaglandin E2 (PGE₂) and cytokines were measured by enzyme-linked immunosorbent assay (ELISA) assay. The mRNA expression of pro-inflammatory genes was determined by qPCR. The total and phosphorylated protein levels were examined by Western blotting. The in vivo anti-inflammatory activities were evaluated by using mouse and zebrafish models.
: PP7 reduced the production of NO and PGE₂ and the protein and mRNA expressions of pro-inflammatory cytokines (
,
, and
) and enzymes (inducible NO synthase
, cyclooxygenase-2
, and Matrix metalloproteinase-9
) in LPS-induced RAW264.7 cells by suppressing the NF-κB and MAPKs pathways. Notably, PP7 markedly inhibited xylene-induced ear edema and cotton pellet-induced granuloma formation in mice and suppressed LPS and CuSO₄-induced inflammation and toxicity in zebrafish embryos.
: This study demonstrates that PP7 exerts strong anti-inflammatory activities in multiple in vitro and in vivo models and suggests that PP7 is a potential novel therapeutic agent for inflammatory diseases.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The aims of this study were to investigate the mechanism underlying the developmental toxicity of fine particulate matter (PM2.5) and provide a more thorough understanding of the toxicity of PM2.5 in ...an ecological environment. Zebrafish embryos at 4 h post-fertilization were exposed to PM2.5 at doses of 200, 300, 400, 500, 600 and 800 μg/mL for 120 h. The mortality, hatching rate, morphology score, body length, locomotor capacity, histological changes, antioxidant defense system, leukocyte migration, inflammation-related gene mRNA expression, endoplasmic reticulum stress (ERS) and autophagy were evaluated to study PM2.5-induced developmental toxicity and its underlying mechanisms. PM2.5 exposure significantly increased the mortality and malformations and reduced the hatching rate and body length of the zebrafish. PM2.5 significantly reduced the locomotor capacity of zebrafish larvae, increased the levels of ROS and disturbed the antioxidant defense system in zebrafish larvae. In addition, a histological examination showed that the heart, liver, intestines and muscle of the PM2.5-treated zebrafish exhibited abnormal changes and a significant increase in cellular autophagic accumulation. RT-PCR showed that the expression of genes related to inflammation (tgfβ and cox2), ERS (hspa5, chop, ire1, xbp1s, and atf6) and autophagy (lc3, beclin1 and atg3) pathways was significantly increased in the PM2.5-treated zebrafish, indicating that PM2.5 induced inflammation and promoted ERS and autophagy responses via the activation of the IRE1-XBP1 and ATF6 pathways. Together, our data indicate that PM2.5 induced a dose- and time-dependent increase in developmental toxicity to zebrafish embryos. Additionally, ERS and autophagy may play important roles in PM2.5-induced developmental toxicity.
ERS and autophagy responses mediated the developmental toxicity induced by PM2.5 in zebrafish embryos. Display omitted
•PM2.5 caused a dose- and time-dependent increase in the developmental toxicity of zebrafish embryos.•PM2.5 reduced the locomotor capacity of zebrafish embryos.•PM2.5 induced inflammation and promoted the ERS and autophagy responses via IRE1-XBP1 and ATF6 pathways.•ERS and autophagy responses mediated the developmental toxicity induced by PM2.5 in zebrafish embryos.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Environmental lead (Pb) exposure is a great hazard to the public health. Although environmentally relevant Pb poisoning is preventable, insidious Pb contaminants are still a major threat to human ...health. Herein, we reported that exposure to Pb at environmentally relevant concentration level (1 μg/L, 10 μg/L and 100 μg/L), disturbed the courtship behavior of adult male zebrafish and further altered the transcriptional patterns of key genes involved in testicular steroidogenesis (igf3, amh, piwil1, lhcgr, fshr, cyp11c1, star, cyp19a1a, cyp19a1b) and apoptosis (bax, cytoC, caspase 9, caspase 3, puma). Both the behavioral and the transcriptional profiles share a similar biphasic dose response, with stimulatory effects after low-level exposure and inhibitory effects after high-level exposure. This results revealed the endocrine disrupting effects of Pb even at an environmentally relevant level within the concentration range of ambient water quality criteria (AWQC) and the reliability of locomotion fingerprint as the indicator for detecting the risk induced by Pb pollution. Current research, for the first time, employed the ZebraTower system as the biological early warning system (BEWS) to find that Pb exerted biphasic effects on the courtship behavior and endocrine regulation of male adult zebrafish. Methodologically, we firstly propose an efficient solution to monitor and assess the risk of Pb exposure by combining the (BEWS) and data analyzing methods such as zebrafish phenomics, which would make a contribution to the detection and prevention of environmentally relevant Pb poisoning.
•Pb of environmentally relevant concentration are of potential reproductive toxicity.•Pb disturbed expression of genes involved in testicular steroidogenesis and apoptosis.•Pb exerted biphasic effects on courtship behavior and endocrine regulation in male.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Pollutant discharges to the aquatic environment often contain multiple environmental stressors, affecting aquatic organisms. To mimic the discharges from nuclear and industry facilities, the combined ...effects of two independent types of stressors, heavy metal Pb and repeated heat pulse were addressed in this study. We investigated the developmental toxicity of combined treatment, especially its toxic effects on zebrafish neurodevelopment. The normal embryos at 4 hpf were exposed to 0.2 mM of Pb dissolved in the bathing medium with different temperatures (30, 32, and 34 °C) and then maintained in an incubator at 28 °C. After performing above treatment once every 24 h for 6 days, we found that combined treatment significantly affected neural development, including loss of dopaminergic (DA) neurons and brain vasculature, disruption of locomotor activity and neurodevelopmental genes expression in a temperature-dependent manner as compared to the Pb alone exposure group, indicating that repeated heat pulse enhances these negative impacts induced by Pb. In contrast, no apparent toxicity was observed in repeated heat pulse alone groups, suggesting that Pb treatment reduces thermal tolerance in zebrafish, which emphasized the importance to evaluate synergistic effects of Pb and repeated heat pulse. Moreover, repeated heat pulse aggravated Pb-induced apoptosis in the zebrafish brain. Further study of the underlying mechanism suggested that Caspase 3 regulated apoptosis was involved in this process. Taken together, our findings shed light on the full understanding of toxic effects of discharges from industrial applications on living organisms and its environmental impact.
•Repeated heat pulse increases Pb-induced developmental toxicity in zebrafish.•Synergistic effects of repeated heat pulse on Pb-induced abnormal neurodevelopment.•Repeated heat pulse enhances Pb-induced suppression on zebrafish locomotor capacity.•Caspase 3 regulated apoptosis is involved in this synergistic process.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Tamoxifen is a clinical drug for estrogen receptor (ER)-positive breast cancer. Recently, it has been detected in aquatic environment. The residual drugs will produce certain biological activity and ...create a risk to aquatic organism when they enter the water environment. Therefore, it has great significance to study the ecotoxicity of tamoxifen. In the study, we used zebrafish as a model of aquatic to investigate the ecotoxic mechanism of tamoxifen to aquatic. We found that tamoxifen induced liver lipid accumulation in zebrafish, which showed a significant hepatotoxicity with smaller liver area and bigger yolk area. Though biochemical and pathologic measurement, tamoxifen treated group showed higher transaminase and lipid content. The elevated liver lipid synthesis might due to the increase of lipid metabolism related gene Srebf1, Srebf2 and Fasn. Moreover, inflammatory cytokine Tnf-α, Il-1β And Il-6 were increased. This result confirmed the toxicity of tamoxifen to aquatic, suggested liver injury was the main characteristic of its ecotoxicity. This study indicated it is important to avoid tamoxifen discharging into the aquatic ecology and provided a theoretical basis of prevention tamoxifen-induced ecotoxicity to aquatic.
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•Residue of tamoxifen in sewage could cause aquatic ecotoxicity.•Tamoxifen-induced toxicity in zebrafish mainly perform as hepatotoxicity.•The mechanism of tamoxifen-induced aquatic liver injury is due to the increase of Srebf1, Srebf2 and Fasn gene.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Isoniazid (INH) is a first-line antituberculosis drug. The incidence of adverse reactions accompanied by inflammation in the liver during drug administration to tuberculosis patients is high and ...severely affects clinical treatment. To better understand the mechanism of hepatotoxicity induced by INH under the inflammatory state, we compared the differences in levels of hepatotoxicity from INH between normal zebrafish and zebrafish in an inflammatory state to elucidate the hepatotoxic mechanism using different endpoints such as mortality, malformation, inflammatory effects, liver morphology, histological changes, transaminase analysis, and expression levels of certain genes. The results showed that the toxic effect of INH in zebrafish in an inflammatory state was more obvious than that in normal zebrafish, that liver size was significantly decreased as measured by liver fatty acid binding protein (LFABP) reporter fluorescence and intensity, and that alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were significantly increased. Hematoxylin and eosin (HE) staining and electron microscopy showed that hepatocyte injury was more obvious in the inflammatory state. In the inflammatory state, INH significantly increased the expression levels of endoplasmic reticulum stress (ERS)-related factors (GRP78, ATF6, PERK, IRE1, XBP1s, GRP94, and CHOP), autophagy-related factors (beclin 1, LC3, Atg3, and Atg12), and apoptosis-related factors (caspase-3, caspase-8, caspase-9, Bax, p53, and Cyt) in larvae. Correlational analyses indicated that the transcription levels of the inflammatory factors interleukin-1b (IL-1b), tumor necrosis factor beta (TNF-β), cyclooxygenase 2 (COX-2), and TNF-ɑ were strongly positively correlated with ALT and AST. Furthermore, the ERS inhibitor sodium 4-phenylbutyrate (4-PBA) could ameliorate the hepatotoxicity of INH-lipopolysaccharide (LPS) in zebrafish larvae. These results indicated that INH hepatotoxicity was enhanced in the inflammatory state. ERS and its mediated autophagy and apoptosis pathways might be involved in INH-induced liver injury promoted by inflammation.
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