Publications by authors named "Zhaoxin Tang"

55 Publications

Arsenic and antimony co-induced nephrotoxicity via autophagy and pyroptosis through ROS-mediated pathway in vivo and in vitro.

Ecotoxicol Environ Saf 2021 Sep 21;221:112442. Epub 2021 Jun 21.

College of Veterinary Medicine, Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou 510642, China. Electronic address:

Arsenic (As) and antimony (Sb) are commonly accumulated environmental pollutants that often coexist in nature and cause serious widespread biological toxicity. To investigate the nephrotoxicity induced by As and Sb in detail, we explored the mechanism by which As and Sb cotreatment induced autophagy and pyroptosis in vivo and in vitro. In this study, mice were treated with 4 mg/kg arsenic trioxide (ATO) or/and 15 mg/kg antimony trichloride (SbCl) by intragastric intubation for 60 days. TCMK-1 cells were treated with ATO (12.5 μM), SbCl (25 μM) or a combination of As and Sb for 24 h. The results of the in vivo experiment demonstrated that As or/and Sb exposure could induce histopathological changes in the kidneys, and increase the levels of biochemical indicators of nephrotoxicity. In addition, As and Sb can co-induce oxidative stress, which further activate autophagy and pyroptosis. In an in vitro experiment, As and/or Sb coexposure increased ROS generation and decreased MMP. Moreover, the results of related molecular experiments further confirmed that As and Sb coactivated autophagy and pyroptosis. In conclusion, our results indicated that As and Sb co-exposure could cause autophagy and pyroptosis via the ROS pathway, and these two metals might have a synergistic effect on nephrotoxicity.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112442DOI Listing
September 2021

Exposure to the herbicide butachlor activates hepatic stress signals and disturbs lipid metabolism in mice.

Chemosphere 2021 Jun 15;283:131226. Epub 2021 Jun 15.

College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. Electronic address:

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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http://dx.doi.org/10.1016/j.chemosphere.2021.131226DOI Listing
June 2021

Long-term copper exposure promotes apoptosis and autophagy by inducing oxidative stress in pig testis.

Environ Sci Pollut Res Int 2021 Jun 15. Epub 2021 Jun 15.

College of Veterinary, South China Agricultural University, Guangzhou, 510642, China.

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.
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http://dx.doi.org/10.1007/s11356-021-14853-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203493PMC
June 2021

Copper induces mitochondria-mediated apoptosis via AMPK-mTOR pathway in hypothalamus of Pigs.

Ecotoxicol Environ Saf 2021 Sep 5;220:112395. Epub 2021 Jun 5.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, Guangdong, PR China. Electronic address:

Copper (Cu), one of the heavy metals, is far beyond the carrying capacity of the environment with Cu mining, industrial wastewater discharging and the use of Cu-containing pesticides. Intaking excess Cu can cause toxic effects on liver, kidney, heart, but few studies report Cu toxicity on brain tissue. It is noteworthy that most toxicity tests are based on rodent models, but large mammals chosen as animal models has no reported. To explore the relationship of the Cu toxicity and mitochondria-mediated apoptosis on hypothalamus in pigs, the content of Cu, histomorphology, mitochondrial related indicators, apoptosis, and AMPK-mTOR signaling pathway were detected. Results showed that Cu could accumulate in hypothalamus and lead to mitochondrial dysfunction, evidenced by the decrease of ATP production, activities of respiratory chain complex I-IV, and mitochondrial respiratory function in Cu-treated groups. Additionally, the genes and proteins expression of Bax, Caspase-3, Cytc in treatment group were higher than control group. Furthermore, the protein level of p-AMPK was enhanced significantly and p-mTOR was declined, which manifested that AMPK-mTOR signaling pathway was activated in Cu-treated groups. In conclusion, this study illuminated that the accumulation of Cu could cause mitochondrial dysfunction, induce mitochondria-mediated apoptosis and activate AMPK-mTOR pathway in hypothalamus.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112395DOI Listing
September 2021

Arsenic (III) and/or Antimony (III) induced disruption of calcium homeostasis and endoplasmic reticulum stress resulting in apoptosis in mice heart.

Ecotoxicol Environ Saf 2021 Sep 4;220:112394. Epub 2021 Jun 4.

Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou 510642, China. Electronic address:

Arsenic (As) and antimony (Sb) are known as an environmental contaminant with cardiotoxicity properties. The endoplasmic reticulum (ER) is the largest calcium reservoir in the cell, and its calcium homeostasis disorder plays a vital role in endoplasmic reticulum stress (ERS) and apoptosis. The objective of this study was to investigate whether As and Sb induced apoptosis via endoplasmic reticulum stress (ERS) linked to calcium homeostasis disturbance. In this study, thirty-two adult mice were gavage-fed daily with AsO (4 mg/kg), SbCl (15 mg/kg) and co-treat with SbCl (15 mg/kg) and AsO (4 mg/kg) daily for 60 days. It was observed that As or/and Sb caused histopathological lesions and ER expansion of the heart. Meanwhile, the gene expression of ER Ca release channels (RyR2 and IP3R) and calmodulin-dependent protein kinase II (CaMKII) increased while the levels of mRNA and protein of ER Ca uptake channel (SERCA2) downregulated significantly compared to the controls. Then, As or/and Sb induced ERS and triggered the ER apoptotic pathway by activating unfolded protein response (UPR)-associated genes ((PERK, ATF6, IRE1, XBP1, JNK, GRP78), and apoptosis-related genes (Caspase12, Caspase3, p53, CHOP). Above indicators in As + Sb group became more severe than that of As group and Sb group. Overall, our results proved that the cardiotoxicity caused by As or/and Sb might be concerning disturbing calcium homeostasis, which induced apoptosis through the ERS pathway.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112394DOI Listing
September 2021

Protective effects of curcumin on ATO-induced nephrotoxicity in ducks in relation to suppressed autophagy, apoptosis and dyslipidemia by regulating oxidative stress.

Ecotoxicol Environ Saf 2021 Aug 19;219:112350. Epub 2021 May 19.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China. Electronic address:

Arsenic trioxide (ATO) has been known as common environmental pollution, and is deemed to a threat to global public health. Curcumin (Cur) is a phytoconstituent, which has been demonstrated to have antioxidant effects. In the current experiment, we investigated the efficacy of Cur against ATO-induced kidney injury and explored the potential molecular mechanisms that have not yet been fully elucidated in ducks. The results showed that treatment with Cur attenuated ATO-induced body weight loss, reduced the content of ATO in the kidney, and improved ATO-induced kidney pathological damage. Cur also remarkably alleviated the ascent of ATO-induced MDA level and activated the Nrf2 pathway. Using the TEM, we found Cur relieved mitochondrial swelling, autolysosomes generating and nuclear damage. Simultaneously, Cur was found that it not only significantly reduced autophagy-related mRNA and protein levels (mTOR, LC3-Ⅰ, LC3-Ⅱ, Atg-5, Beclin1, Pink1 and Parkin) and but also decreased apoptosis-related mRNA and protein expression levels (cleaved caspase-3, Cytc, p53 and Bax). Furthermore, through nontargeted metabolomics analysis, we observed that lipid metabolism balance was disordered by ATO exposure, while Cur administration alleviated the disturbance of lipid metabolism. These results showed ATO could induce autophagy and apoptosis by overproducing ROS in the kidney of ducks, and Cur might relieve excessive autophagy, apoptosis and disturbance of lipid metabolism by regulating oxidative stress. Collectively, our findings explicate the potential therapeutic value of Cur as a new strategy to a variety of disorders caused by ATO exposure.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112350DOI Listing
August 2021

Arsenic exposure induces intestinal barrier damage and consequent activation of gut-liver axis leading to inflammation and pyroptosis of liver in ducks.

Sci Total Environ 2021 Sep 15;788:147780. Epub 2021 May 15.

College of Veterinary Medicine, Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou 510642, China. Electronic address:

Arsenic is an important hazardous metalloid commonly found in polluted soil, rivers and groundwater. However, few studies exist regarding the effect of arsenic trioxide (ATO) on the gut-liver axis and consequent hepatotoxicity in waterfowl. Here, we investigated the influence of ATO on duck intestines and livers, and explored the role of the gut-liver axis in ATO-induced hepatotoxicity and intestinal toxicity. Our results demonstrated that ATO-exposure induced intestinal damage, liver inflammatory cell infiltration and vesicle steatosis. Additionally, the intestinal microbiota community in ATO-exposed ducks displayed significantly decreased α-diversity and an altered bacterial composition. Moreover, ATO-exposure markedly reduced the expression of intestinal barrier-related proteins (Claudin-1, MUC2, ZO-1 and Occludin), resulting in increased intestinal permeability and elevated lipopolysaccharide levels. Simultaneously, ATO-exposure also upregulated pyroptosis-related index levels in the liver and jejunum, and increased pro-inflammatory cytokine production (IFN-γ, TNF-α, IL-18, and IL-1β). Our further mechanistic studies showed that ATO-induced liver and jejunum inflammation were provoked by the activation of the LPS/TLR4/NF-κB signaling pathway and NLRP3 inflammasome. In summary, these results manifested that ATO exposure can cause liver and jejunal inflammation and pyroptosis, and the indirect gut-liver axis pathway may play an essential role in the potential mechanism of ATO-induced hepatotoxicity.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147780DOI Listing
September 2021

Evaluation of toxic effects induced by arsenic trioxide or/and antimony on autophagy and apoptosis in testis of adult mice.

Environ Sci Pollut Res Int 2021 May 20. Epub 2021 May 20.

College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.

Arsenic trioxide (ATO) and antimony (Sb) are well-known ubiquitous environmental contaminants and cause unpromising male reproductive effects in target and non-target exposed organisms. The main objective of this study was to investigate the effects of ATO or/and Sb on process of autophagy, apoptosis, and reproductive organ in adult mice. For this reason, a total of 32 adult mice were randomly divided into different groups like control group, ATO-treated group, Sb-treated group, and combined group. The duration of current experimental trial was 2 months. Various adverse effects of ATO or/and Sb on sperm parameters, oxidative stress, autophagy, and apoptosis were determined in testis of mice. Results indicated that parameters of sperm quality for organ coefficient, sperm count, ratio of sperm survival, testosterone level, and germ cells were significantly decreased, while malformation rate and vacuolization significantly increased in mice exposed to different treatments. Furthermore, the status of antioxidant index of T-AOC, SOD, and MsrB1 levels was reduced, while MDA increased significantly in ATO + Sb group. Results on TEM investigation determined that the autophagosomes, autolysosome, nuclear pyknosis, and chromatin condensation were prominent ailments, and the levels of autophagy and pro-apoptosis indictors including Beclin1, Atg-5, LC3B/LC3A, caspase-8, cytc, cleaved caspase-3, p53, and Bax were up-regulated in treated group, while the content of an anti-apoptosis maker (Bcl-2) was down-regulated. In conclusion, the results of our experiment suggested that abnormal process of autophagy and apoptosis was triggered by arsenic and antimony, and intensity of toxic effects increased in combined treatments of ATO and Sb.
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http://dx.doi.org/10.1007/s11356-021-14486-1DOI Listing
May 2021

Metabolomics and transcriptomics indicated the molecular targets of copper to the pig kidney.

Ecotoxicol Environ Saf 2021 May 1;218:112284. Epub 2021 May 1.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China. Electronic address:

Copper poses huge environmental and public health concerns due to its widespread and persistent use in the past several decades. Although it is well established that at higher levels copper causes nephrotoxicity, the exact mechanisms of its toxicity is not fully understood. Therefore, this experimental study for the first time investigates the potential molecular mechanisms including transcriptomics, metabolomics, serum biochemical, histopathological, cell apoptosis and autophagy in copper-induced renal toxicity in pigs. A total of 14 piglets were randomly assigned to two group (7 piglets per group) and treated with a standard diet (11 mg CuSO per kg of feed) and a high copper diet (250 mg CuSO per kg of feed). The results of serum biochemical tests and renal histopathology suggested that 250 mg/kg CuSO in the diet significantly increased serum creatinine (CREA) and induced renal tubular epithelial cell swelling. Results on transcriptomics and metabolomics showed alteration in 804 genes and 53 metabolites in kidneys of treated pigs, respectively. Combined analysis of transcriptomics and metabolomics indicated that different genes and metabolism pathways in kidneys of treated pigs were involved in glycerophospholipids metabolism and glycosphingolipid metabolism. Furthermore, copper induced mitochondrial apoptosis characterized by increased bax, bak, caspase 3, caspase 8 and caspase 9 expressions while decreased bcl-xl and bcl2/bax expression. Exposure to copper decreased the autophagic flux in terms of increased number of autophagosomes, beclin1 and LC3b/LC3a expression and p62 accumulation. These results indicated that the imbalance of glycosphingolipid metabolism, the impairment of autophagy and increase mitochondrial apoptosis play an important role in copper induced renal damage and are useful mechanisms to understand the mechanisms of copper nephrotoxicity.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112284DOI Listing
May 2021

Long-term exposure to the fluoride blocks the development of chondrocytes in the ducks: The molecular mechanism of fluoride regulating autophagy and apoptosis.

Ecotoxicol Environ Saf 2021 Jul 14;217:112225. Epub 2021 Apr 14.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China. Electronic address:

Long-term exposure to excessive fluoride causes chronic damage in the body tissues and could lead to skeletal and dental fluorosis. Cartilage damage caused by excessive fluoride intake has gained wide attention, but how fluoride accumulation blocks the development of chondrocytes is still unclear. Here, we report a negative correlation between the length and growth plate width after NaF treatments via apoptosis and autophagy, with shrinkage of cells, nuclear retraction, dissolution of chondrocytes. Whereas, fluoride exposure had no significant effect on the number and distribution of the osteoclasts which were well aligned. More importantly, fluoride exposure induced apoptosis of tibial bone through CytC/Bcl-2/P53 pathways via targeting Caspase3, Caspase9, Bak1, and Bax expressions. Meanwhile, the Beclin1, mTOR, Pakin, Pink, and p62 were elevated in NaF treatment group, which indicated that long-term excessive fluoride triggered the autophagy in the tibial bone and produced the chondrocyte injury. Altogether, fluoride exposure induced the chondrocyte injury by regulating the autophagy and apoptosis in the tibial bone of ducks, which demonstrates that fluoride exposure is a risk factor for cartilage development. These findings revealed the essential role of CytC/Bcl-2/P53 pathways in long-term exposure to fluoride pollution and block the development of chondrocytes in ducks, and CytC/Bcl-2/P53 can be targeted to prevent fluoride induced chondrocyte injury.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112225DOI Listing
July 2021

Mosquito-borne infectious diseases in China, 2019.

Travel Med Infect Dis 2021 May-Jun;41:102050. Epub 2021 Apr 2.

College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. Electronic address:

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http://dx.doi.org/10.1016/j.tmaid.2021.102050DOI Listing
July 2021

Environmental fluoride exposure disrupts the intestinal structure and gut microbial composition in ducks.

Chemosphere 2021 Aug 19;277:130222. Epub 2021 Mar 19.

College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. Electronic address:

Fluorine (F) and its compounds produced from industrial production and coal combustion can cause air, water and soil contamination, which can accumulate in animals, plants and humans via food chain threatening public health. Fluoride exposure affects liver, kidney, gastrointestinal and reproductive system in humans and animals. Literature regarding fluoride influence on intestinal structure and microbiota composition in ducks is scarce. This study was designed to investigate these effects by using simple and electron microscopy and 16S rRNA sequencing techniques. Results indicated an impaired structure with reduced relative distribution of goblet cells in the fluoride exposed group. Moreover, the gut microbiota showed a significant decrease in alpha diversity. Proteobacteria, Firmicutes and Bacteroidetes were the most abundant phyla in both control and fluoride-exposed groups. Specifically, fluoride exposure resulted in a significant decrease in the relative abundance of 9 bacterial phyla and 15 bacterial genera. Among them, 4 phyla (Latescibacteria, Dependentiae, Zixibacteria and Fibrobacteres) and 4 genera (Thauera, Hydrogenophaga, Reyranella and Arenimonas) weren't even detectable in the gut microbiota of the ducks. In summary, higher fluoride exposure can significantly damage the intestinal structure and gut microbial composition in ducks.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130222DOI Listing
August 2021

Effects of 25(OH)D supplementation during late gestation on the serum biochemistry and reproductive performance of aged sows and newborn piglets.

J Anim Physiol Anim Nutr (Berl) 2021 Mar 13. Epub 2021 Mar 13.

College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.

The purpose of this study was to investigate the effects of diet type (normal or low Ca and P diets) and 25(OH)D supplementation (with or with not 2000 IU/kg 25(OH)D ) during late gestation on the serum biochemistry and reproductive performance of aged sows and newborn piglets. A total of 40 sows, which are at their 7th parity, were divided into four groups: control group (standard diet), low Ca group, 25(OH)D group and low Ca plus 25(OH)D group respectively (10 in each group). The blood of sows on day 100 and 114 of gestation and newborn piglets was collected for serum biochemical analyses. Results showed that the reproductive performance of sows was not influenced by diet type or 25(OH)D supplementation (p > 0.05). And the addition of 25(OH)D to diet low Ca group caused that the content of serum TG in sows on day 100 of gestation was not different from that of the control group (p > 0.05). The addition of 25(OH)D significantly decreases the content of serum TG in sows on day 114 of gestation (p < 0.05). The addition of 25(OH)D significantly increased the content of serum UREA and CREA in newborn piglets (p < 0.05). Overall, feeding 2000 IU/kg 25(OH)D to aged sows at late gestation had no effects on reproductive performance, but partly contributed to keeping serum TG balance in sows and may indicate increased pressure on kidneys in newborn piglets.
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http://dx.doi.org/10.1111/jpn.13530DOI Listing
March 2021

Arsenic or/and antimony induced mitophagy and apoptosis associated with metabolic abnormalities and oxidative stress in the liver of mice.

Sci Total Environ 2021 Jul 26;777:146082. Epub 2021 Feb 26.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China. Electronic address:

Arsenic and antimony are coexisting cumulative environmental pollutants that cause severe and extensive biological toxicity. However, their interactions and toxic mechanisms in the liver remain to be fully elucidated. In this study, a total of sixty 4-week-old mice were divided into four groups and treated with 4 mg/kg arsenic trioxide (ATO) or/and 15 mg/kg antimony (Sb) for 60 days. The results demonstrated that biochemical indicators of hepatotoxicity (ALT, AST, ALP) were upregulated in all treated groups. Additionally, the oxidative burden of the liver was increased in the cotreated groups compared with the individual toxicant-treated groups. Meanwhile, mitochondrial injury, autophagosomes, hepatic-congestion and karyopyknosis were obviously observed in cotreated groups. Additionally, coupled with serum biochemical index (TG, TC), histopathology examination and metabolomics results, we found that cotreatment with ATO and Sb resulted in lipid metabolism disorder and steatosis of liver tissues. Our further investigation found that the levels of pro-apoptotic (Caspase-3, Caspase-9, Bax, P53, Cytc) and mitophagy (LC3-B, P62, PINK1, Parkin) indexes in the cotreated groups were markedly increased, whereas the levels of anti-apoptosis index (Bcl-2) were decreased. Collectively, these results show that co-exposure to ATO and Sb can cause abnormal liver energy metabolism and oxidative stress. Moreover, mitophagy and apoptosis play important roles in the mechanisms of arsenic/antimony cytotoxicity to mouse livers.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146082DOI Listing
July 2021

Fluorophore-Dapagliflozin Dyad for Detecting Diabetic Liver/Kidney Damages via Fluorescent Imaging and Treating Diabetes via Inhibiting SGLT2.

Anal Chem 2021 03 4;93(10):4647-4656. Epub 2021 Mar 4.

State Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, College of Materials Science and Engineering, South China University of Technology, Guangzhou 510640, China.

Type II diabetes is a prevalent disease; if left untreated, it could cause serious complications including liver and kidney damages. Hence, early diagnosis for these damages and effective treatment of diabetes are of high importance. Herein, a fluorophore-dapagliflozin dyad (DX-B-DA) has been developed as a theranostic system that can be triggered by intrahepatic/intrarenal reactive oxygen species (ROS) to concomitantly release a near-infrared (NIR) fluorescent dye (DX) and a SGLT2 inhibitor dapagliflozin (DA). In this dyad (DX-B-DA), the NIR fluorophore (DX) and the drug DA were covalently linked through a boronate ester bond which serves as the fluorescence quencher as well as the ROS-responsive moiety that can be cleaved by pathological levels of ROS in diabetics. The in vitro experiments indicate that, in the absence of hydrogen peroxide, the dyad is weakly emissive and keeps its drug moiety in an inactive state, while upon responding to hydrogen peroxide, the dyad simultaneously releases the NIR dye and the drug DA, suggesting that it can serve as an activatable probe for detecting and imaging diabetic liver/kidney damages as well as a prodrug for diabetes treatment upon being triggered by ROS. The dyad was then injected in mouse model of type II diabetes, and it is found that the dyad can not only offer visualized diagnosis for diabetes-induced liver/kidney damages but also exhibit high efficacy in treating type II diabetes and consequently ameliorating diabetic liver/kidney damages.
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http://dx.doi.org/10.1021/acs.analchem.1c00223DOI Listing
March 2021

Metabolomics analysis reveals the effect of copper on autophagy in myocardia of pigs.

Ecotoxicol Environ Saf 2021 Apr 18;213:112040. Epub 2021 Feb 18.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, Guangdong, PR China. Electronic address:

Among different synthetic compounds copper (Cu) is persistently and frequently used as growth promoter, antibacterial, antifungal and antiparasitic agent and has become common environmental pollutant. Therefore, this study explores the cardio-toxic effects of control group (10 mg/kg bw Cu) and treatment group (125 and 250 mg/kg bw Cu), and it association with process of autophagy and metabolomics in myocardium of pigs kept in three different experimental treatments for a period of 80 days. The results of serum biochemical parameters showed a significantly increase in creatinine kinase (CK), creatine kinase-MB (CK-MB), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C) and aspartate aminotransferase (AST) in pigs exposed to 125 mg/kg bw and 250 mg/kg bw Cu. Meanwhile, the severe structural abnormalities in cardiomyocytes were found when exposed to 250 mg/kg Cu at day 80. In addition, the mRNA and proteins (Beclin1, ATG5 and LC3II) expression levels were significantly increased and p62 was significantly decreased in cardiomyocytes exposed to 250 mg/kg Cu at day 80 of the trial. Further, UPLC-QTOF/MS technique showed that 7 metabolites were up-regulated and 37 metabolites were down-regulated in cardiomyocytes after 250 mg/kg Cu treatment, with a principal impact on the metabolic pathways including glycerophospholipid metabolism, one carbon pool by folate, fatty acid elongation and fatty acid degradation, which were related to autophagy. Overall, our study identified the autophagy processes and metabolites in metabolic pathways in Cu-induced myocardium injury, which provided useful evidence of myocardium toxicity caused by Cu exposure via metabolomics and multiple bioanalytic methods.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112040DOI Listing
April 2021

The protective role of autophagy against arsenic trioxide-induced cytotoxicity and ROS-dependent pyroptosis in NCTC-1469 cells.

J Inorg Biochem 2021 Apr 12;217:111396. Epub 2021 Feb 12.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China. Electronic address:

Arsenic trioxide (AsO) is widely used in traditional Chinese medicine to treat tumors. This study investigated the effect of As(III) on pyroptosis in murine hepatocytes in vitro and how this relates to autophagy. NCTC1469-cells were treated with As(III) alone (6, 12 and 18 μM) or in combination with N-acetylcysteine (NAC,1 mM), 3-methyladenine (3-MA, 5 mM) or rapamycin (Rapa,100 nM) for 24 h. The results showed that As(III)-treatment reduced cell viability in a dose-dependent manner, but induced lactic dehydrogenase (LDH) activity. As(III)-treatment also resulted in increased intracellular reactive oxygen species (ROS) levels and decreased mitochondrial membrane potential (MMP), therefore promoting pyroptosis. Moreover, As(III)-treatment upregulated the expression of autophagy and pyroptosis-related genes (LC3-A, LC3-B, P62, Beclin-1, Atg5, Caspase-1, Gasdermin D, IL-18, IL-1β) and downregulated the expression of m-TOR, NLRP3, ASC genes. Meanwhile the accumulation of light chain 3-B/A (LC3B/LC3A), autophagy-related gene 5 (Atg-5), Bcl-2-interacting protein (Beclin-1), Caspase-1, Gasdermin D, interleukin-1β (IL-1β), IL-18 and poptosis-associated speck-like protein (ASC) proteins were upregulated while nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) was downregulated in all As(III)-treatment groups. Furthermore, the inhibition of autophagy by 3-MA aggravated AsIII-induced pyroptosis and cytotoxicity. However, NAC or Rapa markedly alleviated the abovementioned phenomenon under As(III) stress. In addition, we speculate that the protective mechanism of NAC on As(III)-induced pyroptosis in hepatocytes mainly include the elimination of ROS because of the chelation of As(III) in the culture medium. In conclusion, these results provide new insight into the mechanisms underlying AsIII-induced cytotoxicity and pyroptosis in hepatocytes in vitro.
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http://dx.doi.org/10.1016/j.jinorgbio.2021.111396DOI Listing
April 2021

Chronic tribasic copper chloride exposure induces rat liver damage by disrupting the mitophagy and apoptosis pathways.

Ecotoxicol Environ Saf 2021 Apr 4;212:111968. Epub 2021 Feb 4.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, Guangdong, PR China. Electronic address:

Despite the fact that copper (Cu) is a vital micronutrient to maintain body function, high doses of Cu through environmental exposure damage various organs, especially the liver, which is the main metabolic organ. To investigate the influence of long-term Cu-induced toxicity on mitophagy and apoptosis in rat liver, 96 seven-month-old male Sprague-Dawley rats were fed TBCC for 24 weeks. The results revealed that exposure to high Cu concentrations could promote oxidative stress liver injury by increasing the hepatic function index (ALT, AST and ALP) and MDA content, while reducing the activity of antioxidant enzymes (T-SOD, GSH-Px and CAT) related to oxidative stress. Consistent with histopathological observations, proper dietary Cu (15-60 mg/kg) could improve antioxidant stress levels and induce a dose-dependent increase in the mRNA expression of mitophagy-related genes, whereas a high Cu concentration (120 mg/kg) could cause severe liver impairment and ultrastructural changes and a reduction in mitophagosomes, accompanied by downregulation of Atg5, Beclin1, Pink1, Parkin, NIX, P62 and LC3B. The expression of apoptosis-related genes (Bax, Bax/Bcl-2, Caspase3, Cytc and p53) and proteins (Caspase3 and p53) was upregulated with the addition of dietary Cu. The results demonstrated that an appropriate dose of TBCC could improve liver function by promoting mitophagy and Cu enzymes that play antioxidative roles, while the accumulation of excess Cu could induce liver lesions by enhancing apoptosis and inhibiting mitophagy pathways.
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http://dx.doi.org/10.1016/j.ecoenv.2021.111968DOI Listing
April 2021

Acetyl-L-Carnitine Induces Autophagy to Promote Mouse Spermatogonia Cell Recovery after Heat Stress Damage.

Biomed Res Int 2021 18;2021:8871328. Epub 2021 Jan 18.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.

Acetyl-L-carnitine (ALC) is an effective substrate for mitochondrial energy metabolism and is known to prevent neurodegeneration and attenuate heavy metal-induced injury. In this study, we investigated the function of ALC in the recovery of mouse spermatogonia cells (GC-1 cells) after heat stress (HS). The cells were randomly divided into three groups: control group, HS group (incubated at 42°C for 90 min), and HS + ALC group (treatment of 150 M ALC after incubated at 42°C for 90 min). After heat stress, all of the cells were recovered at 37°C for 6 h. In this study, the content of intracellular lactate dehydrogenase (LDH) in the cell supernatant and the malondialdehyde (MDA) levels, catalase (CAT) levels, and total antioxidant capacity (T-AOC) were significantly increased in the HS group compared to the CON group. In addition, the mitochondrial membrane potential (MMP) was markedly decreased, while the apoptosis rate and the expression of apoptosis-related genes (Bcl-2, Bax, and caspase3) were significantly increased in the HS group compared to the CON group. Furthermore, the number of autophagosomes and the expression of autophagy-related genes (Atg5, Beclin1, and LC3II) and protein levels of p62 were increased, but the expression of LAMP1 was decreased in the HS group compared to the CON group. However, treatment with ALC remarkably improved cell survival and decreased cell oxidative stress. It was unexpected that levels of autophagy were markedly increased in the HS + ALC group compared to the HS group. Taken together, our present study evidenced that ALC could alleviate oxidative stress and improve the level of autophagy to accelerate the recovery of GC-1 cells after heat stress.
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http://dx.doi.org/10.1155/2021/8871328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837762PMC
May 2021

Cu-induced mitochondrial dysfunction is mediated by abnormal mitochondrial fission through oxidative stress in primary chicken embryo hepatocytes.

J Trace Elem Med Biol 2021 May 23;65:126721. Epub 2021 Jan 23.

College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. Electronic address:

Background: Excess copper (Cu) is an oxidative stress factor which associates with a variety of diseases. The aim of this study was to evaluate the effect of Cu in primary chicken embryo hepatocytes (CEHs).

Methods: CEHs were isolated from 13 days old chicken embryos and followed by different concentration Cu (0, 10, 100, 200 μM) and/or ALC treatment (0.3 mg/mL) for 12 or 24 h. The effects of Cu exposure in CEHs were determined by detecting reactive oxygen species (ROS), malondialdehyde (MDA), mitochondrial membrane potential (MMP), and ATP levels. The expression of mitochondrial dynamics-related genes and proteins were also detected.

Results: Results showed that Cu treatment (100 or 200 μM) significantly decreased CEHs viability, MMP and ATP levels, increased ROS and MDA levels in 12 or 24 h. The up-regulated mitochondrial fission genes and protein in 100 and 200 μM Cu groups suggested Cu promoted mitochondrial division but not fusion. However, the co-treatment of ALC and Cu alleviated those changes compared with the 100 or 200 μM Cu groups.

Conclusion: In conclusion, we speculated that Cu increased the oxidative stress and induced mitochondria dysfunction via disturbing mitochondrial dynamic balance in CEHs, and this process was not completely reversible.
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http://dx.doi.org/10.1016/j.jtemb.2021.126721DOI Listing
May 2021

The hepatotoxicity of altrazine exposure in mice involves the intestinal microbiota.

Chemosphere 2021 Jun 11;272:129572. Epub 2021 Jan 11.

College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. Electronic address:

Atrazine (ATR), a bio accumulative herbicide is frequently used in agriculture to control unwanted weeds. Due to continuous application, atrazine persists in the environment and causes deleterious impacts including neurotoxicity, hepatotoxicity, and gut microbiota disorders. Therefore, this study for the first time reports the variation in the gut microbiota, induction of process of apoptosis and autophagy in mice induced by ATR. Results indicated that TUNEL-positive hepatocytes suggestive of apoptosis were increased in livers of different experimental mice. Results on metabolic analysis in liver tissues indicated an overall change in seventy-six metabolites particularly Uridine 5'-diphosphate, Propenoylcarnitine and Chinenoside V resulting in generation of energy-related metabolic disorders and imbalance of oxidation/autoxidation status. Results on gut microbiome inquisition showed that ATR changed the richness and diversity of gut microbiota of mice and number of Firmicutes. Moreover, results also revealed that ATR induced apoptosis via disruption of apoptotic (Bax, Bcl2, and Casp3) and autophagy (LC3/Map1lc3a, Beclin 1/Becn1 and P62/Sqstm1) genes. Results of our experimental study confirmed that changes in gut microbiota play a significant role in process of gut immune regulation and inflammation via different metabolites. In conclusion, the findings of our study provide a new idea for the involvement of mechanisms of detoxification in liver and inquisition of gut microbiota plays crucial role in regulation of physiological activities through liver-gut axis to mitigate toxic effects in animals.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129572DOI Listing
June 2021

Effects of Long-Term Exposure to Copper on the Keap1/Nrf2 Signaling Pathway and Msr-Related Redox Status in the Kidneys of Rats.

Biol Trace Elem Res 2021 Jan 22. Epub 2021 Jan 22.

College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.

The objective of the present study was to examine the effects of long-term exposure on oxidative damage, Keap1/Nrf2 signaling pathway, and Msr-related redox status in the kidneys of rats. Therefore, in this experimental study, a total of 32 CD-1 rats were randomized into 4 groups and treated with 30-, 60-, and 120-mg/kg Cu for 24 weeks. Different serum biomarkers suggestive of renal functions, pathological changes, and oxidative stress were analyzed in kidney tissues. Moreover, the levels of the Keap1/Nrf2 signaling pathway and redox status-related gene mRNA and proteins were also detected. The results indicated that Cu exposure dramatically increased the contents of creatinine and carbamide. Furthermore, histopathological alterations and mitochondrial damage in kidneys of rats of different Cu-treated groups were obviously observed. In addition, Cu exposure markedly changed the levels of glutathione, catalase, and total antioxidant capacity, and upregulated the contents of protein carbonyl, nitric oxide, and malondialdehyde. Moreover, higher levels of Cu treatments significantly increased the expression of Keap1/Nrf2 signaling pathway and redox status-related genes (NQO1, SOD-1, TRX, MsrA, MsrB1, MsrB2, MsrB3). Simultaneously, the mRNA expression levels of Nrf2, HO-1, and CAT were upregulated in rats exposed to 30- and 60-mg/kg Cu, but downregulated in the 120-mg/kg Cu group compared with the control group. Moreover, the Keap1/Nrf2 signaling pathway and redox status-related protein expression levels (HO-1, SOD-1, TRX, MsrA, MsrB1, MsrB2) were significantly increased in treated rats. In summary, it is suggested that the Keap1/Nrf2 signaling pathway and activation of Msr prevent Cu-induced nephrotoxicity and attenuate oxidative damage.
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http://dx.doi.org/10.1007/s12011-020-02557-2DOI Listing
January 2021

Exposure to copper induces mitochondria-mediated apoptosis by inhibiting mitophagy and the PINK1/parkin pathway in chicken (Gallus gallus) livers.

J Hazard Mater 2021 04 19;408:124888. Epub 2020 Dec 19.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, Guangdong, PR China. Electronic address:

Copper (Cu), a transition metal with essential cellular functions, exerts toxic effects when present in excess by inducing oxidative stress. However, the Cu-induced crosstalk between mitophagy and apoptosis and the underlying mechanisms are unknown. Here, the mechanism of Cu-induced hepatotoxicity mediated by mitophagy and apoptosis was explored in vivo and in vitro. In in vivo experiments, chickens were fed a diet with various levels of Cu (11, 110, 220, and 330 mg/kg) for 7 weeks, which led to ultrastructural damage, mitophagy, and apoptosis in liver tissue. In vitro experiments on primary chicken hepatocytes showed that Cu treatment for 24 h increased the numbers of mitophagosomes and upregulated PINK1, parkin, and p62 mRNA levels and parkin and p62 protein levels, inducing mitophagy. Moreover, treatment with 3- methyladenine (3-MA) aggravated Cu-induced S-phase arrest in cell cycle; increased the apoptotic rate; increased p53, Bak1, Bax, Cyt C, and Caspase3/cleaved-caspase3 mRNA and protein levels; and decreased Bcl2 mRNA and protein levels. However, rapamycin (Rapa) had the opposite effects on the above factors. In general, the results reveal that Cu exposure can cause mitophagy through the PINK1/Parkin pathway in chicken livers, and that mitophagy might attenuate Cu-induced mitochondrial apoptosis.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124888DOI Listing
April 2021

Treatment of tibial dyschondroplasia with traditional Chinese medicines: "Lesson and future directions".

Poult Sci 2020 Dec 8;99(12):6422-6433. Epub 2020 Sep 8.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China. Electronic address:

Tibial dyschondroplasia (TD) is a metabolic tibiotarsal bone disease in rapidly growing birds throughout the world, which is characterized by gait disorders, reduced growth, and in an unrecoverable lameness in many cases. The short production cycle in chickens, long metabolism cycle in most of the drugs with the severe drug residue, and high treatment cost severely restrict the enthusiasm for the treatment of TD. Traditional Chinese medicine (TCM) has been used for the prevention, treatment, and cure of avian bone diseases. Previously, a couple of traditional Chinese medicines has been reported being useful in treating TD. This review will discuss the TCM used in TD and the alternative TCM to treat TD. Selecting a TCM approach and its pharmacologic effects on TD chickens mainly focused on the differentiation, proliferation, and apoptosis of chondrocytes, angiogenesis, matrix metabolism, oxidative damage, cytokines, and calcification of cartilage in tibia.
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http://dx.doi.org/10.1016/j.psj.2020.08.055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704743PMC
December 2020

Copper induces energy metabolic dysfunction and AMPK-mTOR pathway-mediated autophagy in kidney of broiler chickens.

Ecotoxicol Environ Saf 2020 Dec 30;206:111366. Epub 2020 Sep 30.

College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, Guangdong, PR China. Electronic address:

To explore the effects of copper (Cu) on energy metabolism and AMPK-mTOR pathway-mediated autophagy in kidney, a total of 240 one-day-old broiler chickens were randomized into four equal groups and fed on the diets with different levels of Cu (11, 110, 220, and 330 mg/kg) for 49 d. Results showed that excess Cu could induce vacuolar degeneration and increase the number of autophagosomes in kidney, and the adenosine triphosphate (ATP) level and mRNA levels of energy metabolism-related genes were decreased with the increasing dietary Cu level. Moreover, immunohistochemistry and immunofluorescence showed that the positive expressions of Beclin1 and LC3-II were mainly located in cytoplasm of renal tubular epithelial cells and increased significantly with the increasing levels of Cu. The mRNA levels of Beclin1, Atg5, LC3-I, LC3-II, Dynein and the protein levels of Beclin1, Atg5, LC3-II/LC3-I and p-AMPKα1/AMPKα1 were markedly elevated in treated groups compared with control group (11 mg/kg Cu). However, the mRNA and protein levels of p62 and p-mTOR/mTOR were significantly decreased with the increasing levels of Cu. These results suggest that impaired energy metabolism induced by Cu may lead to autophagy via AMPK-mTOR pathway in kidney of broiler chickens.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111366DOI Listing
December 2020

Integration of transcriptomic and metabolomic data reveals metabolic pathway alteration in mouse spermatogonia with the effect of copper exposure.

Chemosphere 2020 Oct 10;256:126974. Epub 2020 May 10.

College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. Electronic address:

Copper is a widespread heavy metal in environment and has toxic effects when exposed. However, study of copper-induced male reproductive toxicity is still insufficient to report, and the underlying mechanisms are unknown. Keeping in view, RNA-Seq and metabolomic were performed to identify metabolic pathways that were distressed in mouse spermatogonia with the effect of copper sulfate, and the integrated analysis of the mechanism of copper administered GC-1 cells from metabolomic and transcriptomic data. Our results demonstrated that many genes and metabolites were regulated in the copper sulfate-treated cells. The differential metabolites analysis showed that 49 and 127 metabolites were significantly different in ESI+ and ESI- mode, respectively. Meanwhile, a total of 2813 genes were up-regulated and 2488 genes were down-regulated in the treatment groups compared to those in the control groups. Interestingly, ophthalmic acid and gamma glutamylleucine were markedly increased by copper treatment in two modes. By integrating with transcriptomic and metabolomic data, we revealed that 37 and 22 most related pathways were over-enriched in ESI+ and ESI- mode, respectively. Whereas, amino acid biosynthesis and metabolism play essential role in the potential relationship between DEGs and metabolites, which suggests that amino acid biosynthesis and metabolism may be the major metabolic pathways disturbed by copper in GC-1 cells. This study provides important clues and evidence for understanding the mechanisms responsible for copper-induced male spermatogenesis toxicity, and useful biomarkers indicative of copper exposure could be discovered from present study.
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http://dx.doi.org/10.1016/j.chemosphere.2020.126974DOI Listing
October 2020

Copper induces oxidative stress with triggered NF-κB pathway leading to inflammatory responses in immune organs of chicken.

Ecotoxicol Environ Saf 2020 Sep 22;200:110715. Epub 2020 May 22.

College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, Guangdong, PR China. Electronic address:

Copper (Cu) is a necessary trace mineral due to its biological activity. Excessive Cu can induce inflammatory response in humans and animals, but the underlying mechanism is still unknown. Here, 240 broilers were used to study the effects of excessive Cu on oxidative stress and NF-κB-mediated inflammatory responses in immune organs. Chickens were fed with diet containing different concentrations of Cu (11, 110, 220, and 330 mg of Cu/kg dry matter). The experiment lasted for 49 days. Spleen, thymus, and bursa of Fabricius (BF) on day 49 were collected for histopathological observation and assessment of oxidative stress status. Additionally, the mRNA and protein levels of NF-κB and inflammatory cytokines were also analyzed. The results indicated that excess Cu could increase the number and area of splenic corpuscle as well as the ratio of cortex and medulla in thymus and BF. Furthermore, excessive Cu intake could decrease activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px); but increase contents of malondialdehyde (MDA), TNF-α, IL-1, IL-1β; up-regulate mRNA levels of TNF-α, IFN-γ, IL-1, IL-1β, IL-2, iNOS, COX-2, NF-κB and protein levels of TNF-α, IFN-γ, NF-κB, p-NF-κB in immune organs. In conclusion, excessive Cu could cause pathologic changes and induce oxidative stress with triggered NF-κB pathway, and might further regulate the inflammatory response in immune organs of chicken.
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http://dx.doi.org/10.1016/j.ecoenv.2020.110715DOI Listing
September 2020

Escherichia coli isolated in pigs, Guangdong, China: Emergence of extreme drug resistance (XDR) bacteria.

J Infect 2020 08 14;81(2):318-356. Epub 2020 May 14.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2020.05.003DOI Listing
August 2020

Copper Induces Apoptosis Through Endoplasmic Reticulum Stress in Skeletal Muscle of Broilers.

Biol Trace Elem Res 2020 Dec 20;198(2):636-643. Epub 2020 Feb 20.

College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, Guangdong, People's Republic of China.

The purpose of this research was to investigate whether copper (Cu) exposure could induce apoptosis via endoplasmic reticulum stress (ERS) in skeletal muscle of broilers. A total of 240 one-day-old chickens were randomly divided into four groups by free access; the diets are as follows: control diet (Cu 11 mg/kg, control group) and high level of Cu diets (Cu 110 mg/kg, group I; Cu 220 mg/kg, group II; Cu 330 mg/kg, group III). The skeletal muscle tissues were collected on day 49 for further examination. The content of Cu, histopathology, and the expression levels of the genes and proteins related to ERS and apoptosis were detected. Results showed that the Cu levels in skeletal muscle were increased in a dose-dependent manner. Meanwhile, the spaces between the muscle fibers were wider with the increase of Cu content, and the myolysis was observed in group III. Besides, the mRNA expression levels of GRP78, GRP94, eIF2α, ATF6, XBP1, CHOP, Caspase-12, and Caspase3 were markedly increased in treated groups compared with control group, and the protein expression levels of GRP78, Caspase3, Active-Caspase3 and JNK were significantly elevated with the increase of dietary Cu. In summary, these findings suggested that Cu could induce apoptosis through ERS in skeletal muscle of broilers.
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http://dx.doi.org/10.1007/s12011-020-02076-0DOI Listing
December 2020

Long-term exposure to copper induces autophagy and apoptosis through oxidative stress in rat kidneys.

Ecotoxicol Environ Saf 2020 Mar 6;190:110158. Epub 2020 Jan 6.

College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. Electronic address:

Copper (Cu) is an essential trace element for most organisms. However, excessive Cu can be highly toxic. The purpose of this study was to elucidate the mechanism underlying Cu toxicity in the kidneys of rats after treatment with CuCl (15 [control], 30, 60, or 120 mg/kg in the diet) for 180 days. Histological and ultrastructural changes, antioxidant enzyme activity, and the mRNA and protein levels of apoptosis and autophagy-related genes were measured. The results showed that Cu exposure led to significant accumulation of copper in kidneys and disorganized kidney morphology. The activities of total anti-oxidation capacity (T-AOC) and superoxide dismutase (SOD) in the kidneys decreased significantly, while the malondialdehyde (MDA) content increased. Furthermore, excessive Cu markedly upregulated the expression of autophagy and apoptosis-related genes (LC3A, LC3B, ATG-5, Beclin-1, Caspase3, CytC, P53, Bax), but downregulated the expression of P62, mTOR and BCL-2. Moreover, the LC3B/LC3A, ATG-5, Beclin-1, P53, Caspase3 proteins were up-regulated while P62 was down-regulated in the kidney tissues of the treatment groups. Overall, these findings provide strong evidence that excess Cu can trigger autophagy and apoptosis via the mitochondrial pathway by inducing oxidative stress in rat kidneys.
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http://dx.doi.org/10.1016/j.ecoenv.2019.110158DOI Listing
March 2020