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Environmental toxicology
John Wiley & Sons Inc.
Environmental toxicology

John Wiley & Sons Inc.

双月刊

1520-4081

Environmental toxicology/Journal Environmental toxicologyISTPEISCI
正式出版
收录年代

    Coleus vettiveroides Root Extract Protects Against Thioacetamide-Induced Chronic Liver Injury by Inhibiting NF-κB Signaling Pathway

    Kadmad Abdul Hameed Mohamed AzarDevaraj EzhilarasanMunusamy KarthickKarthik Shree Harini...
    723-736页
    查看更多>>摘要：The roots of Coleus vettiveroides (CV) have been traditionally used in Indian medicinal systems such as Ayurveda and Siddha for its antioxidant, anti-inflammatory, and antidiabetic effects. This study examines the antifibrotic potential of CV ethanolic root extract (CVERE) against thioacetamide (TAA)-induced liver fibrosis in Wistar rats. TAA was administered via i.p., thrice weekly for 11 weeks to induce liver fibrosis in rats. In separate groups, rats were administered with TAA and were concurrently treated with CVERE 125mg/kg, CVERE 250mg/kg, and silymarin (SIL) 100mg/kg. Liver marker enzymes of hepatotoxicity, oxidative stress markers, proinflammatory marker gene expression (TNF-α, NF-κB, COX, and ILs), fibrotic marker gene expression (collagen Ⅰ and Ⅲ), immune histochemical expression of fibrosis marker proteins, and histopathologic changes were analyzed. TAA administration led to a significant (p < 0.001) increase in the serum level of hepatotoxic marker enzymes. The TAA-treated group showed higher levels (p < 0.001) of MDA and reduced activities of SOD and CAT in the liver. TAA administration increased CYP2E1 expression, proinflammatory, and fibrotic marker gene expressions in rat liver. The histopathology of the liver confirms TAA-induced architectural distortion and fibrotic changes. CVERE and SIL simultaneous treatments significantly protected against TAA-induced oxidative stress, inflammation, and liver fibrosis. In conclusion, CVERE inhibited TAA-induced liver fibrosis through downregu-lation of TAA metabolic activation, redox imbalance, and inflammation through repression of the NF-κB pathway.
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    Effects of Aluminum Oxide Nanoparticles in the Spinal Cord of Male Wistar Rats and the Potential Ameliorative Role of Melatonin

    Nermeen G. AbdelhameedYasmine H. AhmedNoha A. E. YasinMohamed Y. Mahmoud...
    737-749页
    查看更多>>摘要：Aluminum oxide nanoparticles (Al_2O_3 NPs) are widely utilized in vaccine manufacturing and other medical preparations. Melatonin has numerous effects as an antioxidant and anti-apoptotic. The purpose of this study was to examine the beneficial impact of melatonin on Al_2O_3 NPs toxicity in the spinal cord. Forty male rats were divided into four groups: Group Ⅰ, the negative controls (received standard diet and distilled water); Group Ⅱ, Al_2O_3 NPs (received 30mg/kg bw Al_2O_3 NPs); Group Ⅲ, melatonin and Al_O3 NPs (received 30mg/kg bw Al_2O_3 NPs + 10mg/kg bw melatonin); Group Ⅳ, melatonin (received 10mg/kg bw melatonin). All treatments were administered daily for 28 days by gastric gavage. After that, all rats were sacrificed, then, the samples from different spinal cords were subjected to histopathological, biochemical, and immunohistochemical analyses. Al_O_3 NPs markedly elevated malondialdehyde and 8-hydroxydeoxyguanosine while inhibiting superoxide dismutase and catalase. Al_2O_3 NPs also induced histological alterations in both gray and white matter manifested by neuronal degeneration, vacuolation, axonal degeneration, ballooning, and fusion of myelin sheaths. Furthermore, immunohistochemical results displayed a strong positive expression of caspase-3. Conversely, melatonin significantly mitigated the effects of Al_2O_3 NPs by increasing the activities of antioxidant enzymes and inhibiting malondialdehyde and 8-hydroxydeoxyguanosine. Moreover, melatonin alleviated most histological alterations induced by Al_2O_3 NPs and reduced caspase-3 immunoreactivity. Collectively, melatonin could protect the spinal cord and mitigate Al_2O_3, NPs-induced neurotoxicity.
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    Lead Mediated Lipopolysaccharides Exacerbates Fatty Liver Processes in High-Fat Diets-Induced Mice

    Penghui NieLiehai HuTao YouTiantian Jia...
    750-763页
    查看更多>>摘要：Obesity leads to a variety of health risks, and lead, which is ranked second in Agency for Toxic Substances and Disease Registry's priority list of harmful substances, may be more harmful to individuals that are obese. C57BL/6 mice were fed a normal diet or a high-fat diet with or without exposure to 1 g/L lead exposure in drinking water for 8 consecutive weeks. Serum and hepatic biochemistry analysis, histopathological observation, and RT-qPCR were used to explore the potential mechanism of liver damage in obese individuals after Pb exposure, and fecal microbiota transplantation was performed to investigate the role of the gut microbiota in the progression of fatty liver disease. We found that the progression of fatty liver disease induced by high-fat diets was accelerated by chronic lead intake. In addition, the occurrences of liver injury in recipient mice suggested the role of the gut microbiota. These findings indicated that the combination of lead and a HFD exacerbated hepatic lipotoxicity by activating LPS-mediated inflammation, and that gut microbiota disorders and impaired intestinal barrier function play pivotal roles in the progression of fatty liver disease.
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    Berberine Attenuates Cerulein-Induced Acute Pancreatitis by Modulating Nrf2/NOX2 Signaling Pathway via AMPK Activation

    Sapana P. BansodMohd Aslam SaifiShrilekha ChilveryNandkumar Doijad...
    764-773页
    查看更多>>摘要：AMP-activated protein kinase (AMPK) is the master regulator of cellular energy which gets activated during energy stress and restores tissue homeostasis. AMPK is widely expressed in the pancreas and is involved in protein synthesis. In cerulein-induced acute pancreatitis (AP), diminished AMPK activity in the pancreatic tissue may be associated with pancreatic inflammation and oxidative stress. Our results demonstrated that berberine (BR) treatment produced significant decrease in plasma amylase and lipase levels and improved histopathological features in AP mice model. Myeloperoxidase (MPO) activity indicated that BR suppressed the infiltration of neutrophils in pancreas. BR treatment markedly decreased the levels of proinflammatory cytokines including interleukins (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α) via inhibition of nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) expression. In addition, BR activates the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling and inhibits cerulein-induced oxidative-nitrosative stress. Mechanistically, we found inhibition of AMPK activity in cerulein-induced AP, while BR-treated animals showed marked increase in the AMPK expression. Together, our study indicated that BR-mediated AMPK activation in pancreatic tissues demonstrated attenuation of cerulein-induced oxidative stress and inflammation. Based on our observations, further exploration of this promising natural product against AP and associated complications may lead to promising therapeutic options.
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    The Sub-Acute Potential Risk of Oxamyl in Male Albino Rats

    Maher S. SalamaKhaled A. OsmanRania Elbanna
    774-786页
    查看更多>>摘要：The current study aimed to investigate the sub-acute effects of oxamyl on male Albino rats following oral administration of either 0.031 or 0.31 mg/kg/day for 14 consecutive days. The findings demonstrated that oxamyl produced a significant impact on most of the examined blood profile and biomarkers, along with a significant progressive and discernible alterations in the histology of organs. According to the results obtained, the potential mechanisms by which oxamyl causes its toxic effects on rats are identified as the inflammation indices, the inhibition of transaminases, alkaline phosphatase, and antioxidant enzymes, as well as the production of thiobarbituric acid reactive substances (TBARs) in organs following oxamyl treatment based on histopathological examinations. Due to the substantial genetic similarities between rats and humans, it is therefore anticipated that oxamyl will have comparable detrimental effects on humans.
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    Zeolite Imidazole Framework-8 Exacerbates Astrocyte Activation and Oxidative Stress in the Brain of Rats

    SadafAbdiMoein ShirzadMaryam Ghasemi-KasmanLeyla Nadalinezhad...
    787-801页
    查看更多>>摘要：Metal-organic frameworks (MOFs) have been gaining significant attention due to their potential application in medicine. Here, we investigated the effect of zeolite imidazole framework-8 (ZIF-8) on neuro-behavioral parameters, histopathology, inflammation, and oxidative stress levels of rats' brain samples. Forty-eight male Wistar rats were injected by four injections of saline or ZIF-8 at different doses of 5,10, or 20mg/kg via the caudal vein. Y-Maze, Morris-Water Maze (MWM), and three chamber tests were conducted to explore working memory, spatial learning and memory, and social interactions, respectively. Histological staining and immunohistochemistry were used to evaluate pathological changes and astrocyte activation levels. The inflammation levels were measured using quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR). The total antioxidant capacity (TAC) and oxidative stress production were assessed by biochemical assays. The results showed that ZIF-8 induces neuromotor impairment dose-dependently. Although histopathological studies indicated increased neuronal loss, inflammatory changes, and elevated active astrocytes in the hippocampus, the expression levels of IL-1β and TNF-α were not significantly increased in ZIF-8-treated rats. The TAC level significantly reduced and the malondialdehyde (MDA) level remarkably increased in the brain tissues. Our findings suggest that administration of ZIF-8 induce neuromotor impairment, probably through amplified inflammation and oxidative stress.
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    Combined Effect of Nanoparticles of Silver and Silica to HeLa Cells: Synergistic Internalization and Toxicity

    Chen-Si LiJie LiuQiangqiang ZhangXue-Rui Tang...
    802-816页
    查看更多>>摘要：The wide range of applications and the enormous production of nanomaterials have raised the possibility that humans may simultaneously contact with various nanomaterials through multiple routes. Although numerous toxicity studies have been conducted on the toxicity of nanomaterials, knowledge of the combined toxicity of nanomaterials remains limited. Herein, the combined toxic effects of the two types of the most widely used nanomaterials, silver and silica, were studied on HeLa cells. In addition, considering there may have possible interplay between nanoparticles of different sizes, two different-sized silica nanoparticles (SNPs) were used. The results indicate that compared with individual exposure, the combined exposure to 35 nm silver nanoparticles (Ag35) and 40 nm or 120 nm SNPs (SNP40 or SNP120) at individual non-toxic concentrations causes more severe cytotoxicity, manifested by the ROS overgeneration, decreased mitochondrial membrane potential and ATP level, and increased apoptosis/necrosis. The internalized Ag35 and its dissolved Ag ions that are delivered into cells by adsorbing on SNPs are identified as the primary contributors to the combined toxicity. Although the cytotoxicity of the mixed Ag35 and SNP40 is comparable to that of the mixed Ag35 and SNP120, there are noticeable differences in their intracellular contents and their sub-cellular locations due to size effects. This study provides in-depth insights into the combined toxicity of inorganic nanoparticles and highlights the importance of the size effect of nanoparticles in their nanotoxicity assessment.
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    Effects of Environmentally Relevant Concentrations of Roundup on Oxidative-Nitrative Stress, Cellular Apoptosis, Prooxidant-Antioxidant Homeostasis, Renin and CYP1A Expressions in Goldfish: Molecular Mechanisms Underlying Kidney Damage During Roundup Exposure

    Md Imran NoorMd Saydur Rahman
    817-834页
    查看更多>>摘要：Roundup is one of the most widely used glyphosate-based harmful herbicides in the United States as well as globally, which poses a severe risk for terrestrial and aquatic organisms. In order to identify the detrimental effects of Roundup exposure in aquatic organisms, we investigated the environmentally relevant concentrations of Roundup exposure (low dose: 0.5 μg/L and high dose: 5.0 μg/L for 2 weeks) on renin expression, oxidative-nitrative stress biomarkers (e.g., 2,4-dinitrophenol, DNP; and 3-nitrotyrosine protein, NTP), prooxidant-antioxidant enzymes expressions (e.g., superoxide dismutase, SOD; and catalase, CAT), cellular apoptosis, and cytochrome P450 1A (CYP1A) mRNA levels in the kidneys of goldfish (Carassius auratus). Histopathological and in situ TUNEL analyses showed widespread tissue disruption (e.g., bowman's capsule shrinkage, melanin pigment formation, etc.) and induced apoptotic nuclei in the kidneys of goldfish. Immunohistochemical and quantitative real-time PCR (qRT-PCR) analyses showed a significant (p<0.05) increase in the expression of renin, DNP, NTP, SOD, and CAT, as well as CYP1A mRNA levels in the kidneys of fish exposed to Roundup. These results suggest that environmentally relevant concentrations of Roundup disrupt kidney architecture by inducing oxidative-nitrative stress, cellular apoptosis, and change in osmoregulatory enzymes (i.e., renin) and prooxidant-antioxidant systems in the kidneys of teleost fishes.
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    Fluoride Exposure Modulates Skeletal Development and Mineralization in Zebrafish Larvae

    Harsheema OttappilakkilEkambaram Perumal
    835-847页
    查看更多>>摘要：The presence of high levels of fluoride (F) in groundwater is a major issue worldwide. Although F is essential for healthy teeth and bones, excessive exposure can cause fluorosis or F toxicity. This condition primarily affects the hard tissues due to their high F retention capacity. F accumulation alters bone formation and resorption mechanisms interfering with mineral homeostasis and eventually manifests as skeletal fluorosis. Albeit the numerous studies on skeletal fluorosis, the effect of F on developmental osteogenesis is inconclusive. In light of this, we studied the effect of F on osteogenic differentiation, bone development, and mineralization in zebrafish. Zebrafish embryos were subjected to a low (25 ppm NaF), and a moderately high (50 ppm NaF) dose, along with a control (E3 medium alone) until 7 days postfertilization (dpf). The F content in the larvae was quantified to reveal a dose-dependent increase in the exposed groups. Alizarin Red and alkaline phosphatase (ALP) staining suggested enhanced mineralization in the F-treated groups. Quantitative analyses of the ALP activity and hydroxyproline (Hyp) content revealed sim-ilar results. Alcian blue staining of pharyngeal cartilages showed that F exposure alters the morphology of the major cartilages, indicating a possible craniofacial defect. Moreover, gene expression analyses of the bone markers associated with osteogenic differentiation, early mineralization, and remodeling (runx2a/b, brnp4, ocn, osx, collal, alp, rank, rankl, and opg) showed enhanced expression in the low F group. While the 50 ppm F group showed a decline in osteogenic activity, a considerable increase in the expression of mineralization markers was observed. The expression levels of cartilage markers sox9a and sox9b, remained insignificant, indicating the effect of F toxicity on osteogenesis and mineralization. Also, F exposure interferes with bone metabolism through altered osteogenic differentiation, development, and mineralization in zebrafish larvae.
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    Intervention of a Communication Between PI3K/Akt and β-Catenin by (-)-Epigallocatechin-3-Gallate Suppresses TGF-/β1-Promoted Epithelial-Mesenchymal Transition and Invasive Phenotype of NSCLC Cells

    Li-Sung HsuChih-Li LinMin-Hsiung PanWei-Jen Chen...
    848-859页
    查看更多>>摘要：The epithelial-mesenchymal transition (EMT) assists in the acquisition of invasiveness, relapse, and resistance in non-small cell lung cancer (NSCLC) and can be caused by the signaling of transforming growth factor-β1 (TGF-β1) through Smad-mediated or Smad-independent pathways. (-)-Epigallocatechin-3-gallate (EGCG), a multifunctional cancer-preventing bio-constituent found in tea polyphenols, has been shown to repress TGF-β1-triggered EMT in the human NSCLC A549 cell line by inhibiting the activation of Smad2 and Erk1/2 or reducing the acetylation of Smad2 and Smad3. However, its impact on the Smad-independent pathway remains unclear. Here, we found that EGCG, similar to LY294002 (a specific inhibitor of phosphatidylinositol 3-kinase [PI3K]), downregulated Akt activation and restored the action of glycogen synthase kinase-3β (GSK-3β), accompanied by TGF-β1-caused changes in hallmarks of EMT such as N-cadherin, E-cadherin, vimentin, and Snail in A549 cells. EGCG inhibited β-catenin expression and its nuclear localization caused by TGF-β1, suggesting that EGCG blocks the crosstalk between the PI3K/Akt/GSK-3β route and β-catenin. Furthermore, it was shown that EGCG suppressed TGF-β1-elicited invasive phenotypes of A549 cells, including invading and migrating activities, matrix metalloproteinase-2 (MMP-2) secretion, cell adhesion, and wound healing. In summary, we suggest that EGCG inhibits the induction of EMT by TGF-β1 in NSCLC not only through a Smad-dependent pathway, but also through the regulation of the PI3K/Akt/β-catenin signaling axis.
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