Copper (Cu) is a heavy metal which is being used widely in the industry and agriculture. However, the overuse of Cu makes it a common environmental pollutant. In order to investigate the testicular ...toxicity of Cu, the pigs were divided into three groups and were given Cu at 10 (control), 125, and 250 mg/kg body weight, respectively. The feeding period was 80 days. Serum hormone results showed that Cu exposure decreased the concentrations of follicular stimulating hormone (FSH) and luteinizing hormone (LH) and increased the concentration of thyroxine (T4). Meanwhile, Cu exposure upregulated the expression of Cu transporter mRNA (Slc31a1, ATP7A, and ATP7B) in the testis, leading to increase in testicular Cu and led to spermatogenesis disorder. The Cu exposure led to an increased expression of antioxidant-related mRNA (Gpx4, TRX, HO-1, SOD1, SOD2, SOD3, CAT), along with increase in the MDA concentration in the testis. In LG group, the ROS in the testis was significantly increased. Furthermore, the apoptotic-related mRNA (Caspase3, Caspase8, Caspase9, Bax, Cytc, Bak1, APAF1, p53) and protein (Active Caspase3) and the autophagy-related mRNA (Beclin1, ATG5, LC3, and LC3B) expression increased after Cu exposure. The mitochondrial membrane potential in the testicular tissue decreased, while the number of apoptotic cells increased, as a result of oxidative stress. Overall, our study indicated that the Cu exposure promotes testicular apoptosis and autophagy by mediating oxidative stress, which is considered as the key mechanism causing testicular degeneration as well as dysfunction.
Fluorine being a well-known and essential element for normal physiological functions of tissues of different organisms is frequently used for growth and development of body. The mechanisms of adverse ...and injurious impacts of fluoride are not clear and still are under debate. Therefore, this study was executed to ascertain the potential mechanisms of sodium fluoride in liver tissues of ducks. For this purpose, a total of 14 ducks were randomly divided and kept in two groups including control group and sodium fluoride treated group. The ducks in control group were fed with normal diet while the ducks in other group were exposed to sodium fluoride (750 mg/kg) for 28 days. The results showed that exposure to sodium fluoride induced deleterious effects in different liver tissues of ducks. The results indicated that mRNA levels of Cas-3, Cas-9, p53, Apaf-1, Bax and Cyt-c were increased in treated ducks with significantly higher mRNA level of Cas-9 and lower levels of the mRNA level of Bcl-2 as compared to untreated control group (P < 0.01). The results showed that protein expression levels of Bax and p53 were increased while protein expression level of Bcl-2 was reduced in treated ducks. No difference was observed in protein expression level of Cas-3 between treated and untreated ducks. The results of this study suggest that sodium fluoride damages the normal structure of liver and induces abnormal process of apoptosis in hepatocyte, which provide a new idea for elucidating the mechanisms of sodium fluoride induced hepatotoxicity in ducks.
•Long-term exposure NaF induced hepatotoxicity in ducks.•NaF exposure caused liver granule and vacuolar degeneration observed by histological analysis.•The mechanism of NaF exposure on hepatotoxicity involving activating autophagy and apoptosis.•Cyt-C/Caspase 3/9 signaling pathway activation target cell death.
Alfalfa, an essential forage crop known for its high yield, nutritional value, and strong adaptability, has been widely cultivated worldwide. The yield and quality of alfalfa are frequently ...jeopardized due to environmental degradation. Lignin, a constituent of the cell wall, enhances plant resistance to abiotic stress, which often causes osmotic stress in plant cells. However, how lignin responds to osmotic stress in leaves remains unclear. This study explored the effects of osmotic stress on lignin accumulation and the contents of intermediate metabolites involved in lignin synthesis in alfalfa leaves. Osmotic stress caused an increase in lignin accumulation and the alteration of core enzyme activities and gene expression in the phenylpropanoid pathway. We identified five hub genes (CSE, CCR, CADa, CADb, and POD) and thirty edge genes (including WRKYs, MYBs, and UBPs) by integrating transcriptome and metabolome analyses. In addition, ABA and ethylene signaling induced by osmotic stress regulated lignin biosynthesis in a contradictory way. These findings contribute to a new theoretical foundation for the breeding of high-quality and resistant alfalfa varieties.
Dagangshan hydropower station is located in the middle of
Dadu River
, Southwest China. Many diabase dikes were exposed in the adamellite granite body during excavation of the underground caverns. ...The dikes are highly directional, have crushed interiors, exhibit strong alteration, and have poor contact relationships with surrounding rocks, all of which is inconsistent with the characteristics of typical diabase. This paper describes systematic research that focused on the dikes’ spatial distribution, macroscopic characteristics, physical and mechanical properties, and common instability modes. Factors influencing their stability and their corresponding control measurements are discussed in the context of the site and its conditions. Results show that most of the dikes located in the underground caverns are the branches of the main dike β9, which produced from a strong basic magma extrusion–overflow event happened in between the
Permian
and
Triassic
. Due to multiple strong tectonic activities, the chlorite alignment of these dikes generally tended to be significant and leaded the physical and mechanical properties to be poor. Then, excavation and repetitive blasts resulted in strong disturbances to the original dikes and even caused rock unloading (collapse, rock block fall) and groundwater runoff system (water inflow) change. According to the common instability modes and reasons of diabase dikes, some specific control measures including solidified rubbles, reinforcement methods, pre-grouting, and small ducts are implemented in order to keep the surrounding of diabase safety, and the results show that the control methods perform a proper effect on these engineering problems.
The rapid development of new energy battery enterprises manifolds the obsolete and scrapped batteries which are considered serious concern for the environment and ecology. Increasing trend of ...recycling batteries waste is public hazard throughout the world. The batteries wastes affect the various body systems but exact toxicological mechanism of battery wastewater is still unexplored. The present study was designed to observe the toxicological effects of batteries wastes on kidney functional dynamics. In this experiment, a total of 20 male mice were randomly divided into two groups including control and treatment (battery wastewater) group. The control group was provided the normal saline while the battery wastewater group were provided battery waste-water for a period of 21 days. The isolated kidneys were processed for histopathological analysis, biochemical assays, mRNA and protein estimation. The results showed that battery wastewater provision increased the mitochondrial division-related genes and proteins (Drp1, MFF, Fis1) and decreased the expression level of fusion-related nuclear proteins (MFN1, MFN2, OPA1) in kidneys. Moreover, the battery wastewater exposure significantly up-regulated the autophagy (PINK, Parkin, mTOR, ATG5, LC3-b, p62) and apoptosis (Bax, Cytc, APAF1, P53, Caspase3, Caspase8) related mRNA and proteins levels in kidneys. However, down-regulation of mRNA and proteins levels of Bcl2 and Beclin1 were also observed in kidneys after batteries wastes exposure. In conclusion, it is evident that the battery wastewater leads to renal apoptosis and autophagy by disrupting the mitochondrial dynamics in mice kidneys.
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•Battery wastewater exposure damages kidney deconstruction and induces renal inflammation.•Battery wastewater exposure induces kidney mitochondrial-mediated apoptosis.•The disorder of mitochondrial dynamics promotes apoptosis.•Battery wastewater exposure induces nephrotoxicity via elevating autophagy.
As the primary source of electricity for various devices, batteries are important contributors to the overall electronic waste generated; and are widely considered a source of highly ecotoxic ...pollutants. Material leakage in battery manufacturing has not been completely solved, and the elucidation of the toxic mechanisms of battery wastewater exposure is needed. We demonstrated that battery waste exposure disrupted the intestinal flora and aggravated hepatotoxicity via the gut-liver axis. Under battery waste exposure, colon epithelium suffered physiological damage, and gene and protein expression levels related to gut barrier function (ZO-1, claudin-1, and Occludin) were significantly downregulated. Meanwhile, battery waste reduced the richness and diversity of the flora, causing metabolites produced by intestinal microbes to enter the gut-liver axis. Gut microbial dysbiosis impaired mitochondrial respiratory function in liver tissue cells, and mitophagy, apoptosis, and the disorder of glycolipids and amino acid metabolism were induced in hosts exposed to battery toxins. Altogether, these results provided novel insights into the underlying mechanisms of battery wastewater-related hepatotoxicity induced by gut microbiota via the gut–liver axis, which has public health implications where humans and animals are exposed to industrial toxins generated by uncontained battery disposal.
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•Battery wastewater disturbed the gut microbiota and increased the potential pathogenicity.•Battery wastewater induced gut leakage by reducing tight junction protein expression.•Mitophagy and apoptosis were involved in battery wastewater-induced hepatotoxicity.•Mechanism of gut-liver axis provided a novel insight into the battery wastewater toxicity.
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•Exposure to the Zearalenone results in hepatotoxicity, which altered liver function and damage liver structure.•Zearalenone exposure induced apoptosis and autophagy in hepatocytes ...via mitochondrial apoptosis and Beclin1 autophagy signaling pathway.•Zearalenone significantly altered the variation of 91 metabolites, which mainly involved in glycerophospholipid metabolism pathway.•Zearalenone affect the liver via interaction of gut microbiome and metabolites.
Zearalenone (ZEN), a mycotoxin is frequently detected in different food products and has been widely studied for its toxicity. However, the underlying mechanisms of hepatotoxic effects, relationship between gut microbiome and liver metabolite mediated hepatotoxicity mechanisms induced by ZEN are still not clear. Here, we reported that the different microscopic changes like swelling of hepatocyte, disorganization of hepatocytes and extensive vacuolar degeneration were observed, and the mitochondrial functions decreased in exposed mice. Results exhibited up-regulation in expression of signals of apoptosis and autophagy in liver of treated mice via mitochondrial apoptotic and autophagy pathway (Beclin1/p62). The diversity of gut microbiome decreased and the values of various microbiome altered in treated mice, including 5 phyla (Chloroflexi, Sva0485, Methylomirabilota, MBNT15 and Kryptonia) and genera (Frankia, Lactococcus, Anaerolinea, Halomonas and Sh765B-TzT-35) significantly changed. Liver metabolism showed that the concentrations of 91 metabolite including lipids and lipid like molecules were significantly changed. The values of phosphatidylcholine, 2-Lysophosphatidylcholine and phosphatidate concentrations suggestive of abnormal glycerophosphate metabolism pathway were significantly increased in mice due to exposure to ZEN. In conclusion, the findings suggest that the disorders in gut microbiome and liver metabolites due to exposure to ZEN in mice may affect the liver.
Butachlor is a systemic herbicide widely applied on wheat, rice, beans, and different other crops, and is frequently detected in groundwater, surface water, and soil. Therefore, it is necessary to ...investigate the potential adverse health risks and the underlying mechanisms of hepatotoxicity caused by exposure to butachlor in invertebrates, other nontarget animals, and public health. For this reason, a total of 20 mice were obtained and randomly divided into two groups. The experimental mice in one group were exposed to butachlor (8 mg/kg) and the mice in control group received normal saline. The liver tissues were obtained from each mice at day 21 of the trial. Results indicated that exposure to butachlor induced hepatotoxicity in terms of swelling of hepatocyte, disorders in the arrangement of hepatic cells, increased concentrations of different serum enzymes such as alkaline phosphate (ALP) and aspartate aminotransferase (AST). The results on the mechanisms of liver toxicity indicated that butachlor induced overexpression of Apaf-1, Bax, Caspase-3, Caspase-9, Cyt-c, p53, Beclin-1, ATG-5, and LC3, whereas decreases the expression of Bcl-2 and p62 suggesting abnormal processes of apoptosis and autophagy. Results on different metabolites (61 differential metabolites) revealed upregulation of PE and LysoPC, whereas downregulation of SM caused by butachlor exposure in mice led to the disruption of glycerophospholipids and lipid metabolism in the liver. The results of our experimental research indicated that butachlor induces hepatotoxic effects through disruption of lipid metabolism, abnormal mechanisms of autophagy, and apoptosis that provides new insights into the elucidation of the mechanisms of hepatotoxicity in mice induced by butachlor.
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•Exposure to the herbicide butachlor results in hepatotoxicity.•Butachlor exposure induced apoptosis and autophagy in hepatocytes.•Butachlor significantly altered the variation of 61 metabolites and disturbed lipid metabolism.•PE and LysoPC disturbed the glycerophospholipid metabolism under butachlor exposure.
Thiram, a well-known sulfur containing organic compound is frequently and extensively used in agriculture because of high biological activity to control different pests. In certain cases, due to long ...persistence in the environment pesticides and other environmental contaminants induce undesirable toxic impacts to public health and environment. To ascertain the potential mechanisms of toxicity of thiram on different immune organs of broilers, a total of 100 one-day-old chicks were obtained and randomly divided into two groups including thiram group (50 mg/kg) and untreated control group. Thymus and spleen tissues were collected at the age of 14 days from the experimental birds. At necropsy level, thymus was congested, enlarged and hyperemic while spleen had no obvious lesions. The results on mechanisms (apoptosis and autophagy) of immunotoxicity showed significantly increased expression of bax, caspase3, cytc, ATG5, beclin1 and p62 in spleen of treated mice. Results indicated significantly decreased expression of m-TOR and bcl2 to activate apoptosis and autophagy. The expressions of bax, p53 and m-TOR were up-regulated in the thymus while the expressions of ATG5 and Beclin1 were down-regulated to mediate cell apoptosis and inhibit autophagy. The results on different metabolome investigation showed that the sphingolipid metabolism in the thymus of chicks exposed to thiram was disrupted resulting in up-regulation of metabolites related to cell membrane components such as SM, galactosylceramide and lactosylceramide. The results of our experimental research suggest that thiram can interfere with the sphingolipid metabolism in thymus and angiogenesis, inhibit the proliferation of vascular endothelial cells to induce potential toxic effects in chicken.
Butachlor being an important member of chloroacetanilide herbicides, is frequently used in agriculture to control unwanted weeds. Exposure to butachlor can induce cancer, human lymphocyte aberration, ...and immunotoxic effects in animals. The current experimental trial was executed to determine the potential risks of herbicide butachlor to immunotoxicity and its mechanism of adverse effects on the spleen. For this purpose, mice were exposed to 8 mg/kg butachlor for 28 days, and the toxicity of butachlor on the spleen of mice was evaluated. We found that butachlor exposure led to an increase in serum ALB, GLU, TC, TG, and TP and changes in the morphological structure of the spleen of mice. More importantly, results showed that butachlor significantly increased the expression level of ATG-5, decreased the protein expression of LC3B and M-TOR, and significantly decreased the mRNA content of M-TOR and p62. Results revealed that the mRNA contents of APAF-1, CYTC, and CASP-9 related genes were significantly decreased after butachlor treatment. Subsequently, the mRNA levels of inflammatory cytokines (IL-1β, TNF-α, IL-10) were reduced in the spleen of treated mice. This study suggested that butachlor induce spleen toxicity and activate the immune response of spleen tissue by targeting the CYTC/BCL2/M-TOR pathway and caspase cascading activation of spleen autophagy and apoptosis pathways which may ultimately lead to immune system disorders.
•Exposure to the butachlor has the potential risks to immunotoxicity.•Butachlor exposure induced apoptosis and autophagy in spleen.•CYTC/Bcl-2/mTOR pathway and caspase cascading activation target cell death.•Butachlor induce spleen toxicity and activate the immune response.
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