Publications by authors named "Qingyue Han"

16 Publications

  • Page 1 of 1

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

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

Evolutionary and genomic comparisons of hybrid uninucleate and nonhybrid Rhizoctonia fungi.

Commun Biol 2021 Feb 15;4(1):201. Epub 2021 Feb 15.

Key Laboratory of Pest Monitoring and Green Management, MOA; Joint Laboratory for International Cooperation in Crop Molecular Breeding; Department of Plant Pathology, China Agricultural University, Beijing, China.

The basidiomycetous fungal genus, Rhizoctonia, can cause severe damage to many plants and is composed of multinucleate, binucleate, and uninucleate species differing in pathogenicity. Here we generated chromosome-scale genome assemblies of the three nuclear types of Rhizoctonia isolates. The genomic comparisons revealed that the uninucleate JN strain likely arose by somatic hybridization of two binucleate isolates, and maintained a diploid nucleus. Homeolog gene pairs in the JN genome have experienced both decelerated or accelerated evolution. Homeolog expression dominance occurred between JN subgenomes, in which differentially expressed genes show potentially less evolutionary constraint than the genes without. Analysis of mating-type genes suggested that Rhizoctonia maintains the ancestral tetrapolarity of the Basidiomycota. Long terminal repeat-retrotransposons displayed a reciprocal correlation with the chromosomal GC content in the three chromosome-scale genomes. The more aggressive multinucleate XN strain had more genes encoding enzymes for host cell wall decomposition. These findings demonstrate some evolutionary changes of a recently derived hybrid and in multiple nuclear types of Rhizoctonia.
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http://dx.doi.org/10.1038/s42003-021-01724-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884421PMC
February 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

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

J Hazard Mater 2021 Apr 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

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

Composite Polymer Electrolyte Incorporating Metal-Organic Framework Nanosheets with Improved Electrochemical Stability for All-Solid-State Li Metal Batteries.

ACS Appl Mater Interfaces 2020 May 23;12(18):20514-20521. Epub 2020 Apr 23.

School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China.

Composite polymer electrolytes using polyethylene oxide (PEO) are highly appealing by virtue of the fine electrochemical stability, inexpensiveness, and easy fabrication. However, their practical application is currently hindered by the insufficient room-temperature ionic conductivity. Herein, nickel-based ultrathin metal-organic framework nanosheets (NMS) are first introduced as a novel 2D filler into the PEO matrix. The introduction of NMS with a high aspect ratio effectively improves the amorphous region proportion of PEO and thus enhances the ionic conductivity of the electrolyte by 1 order of magnitude. In addition, the Lewis acid-base interactions between the surface-coordinated unsaturated Ni atoms in NMS and the anions of lithium salt could promote the dissociation of lithium salt. Hence, the composite electrolyte with NMS achieves a high Li transference value of 0.378. Along with the unique nanostructure of NMS, this NMS composite electrolyte also suppresses Li dendrite growth during cycling. As a result, the assembled all-solid-state Li/LiFePO battery demonstrates a high reversible capacity of 130 mA h g at 0.1 C and 30 °C for 50 cycles.
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http://dx.doi.org/10.1021/acsami.0c03430DOI Listing
May 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

Tape-Casting Li La TiO Ceramic Electrolyte Films Permit High Energy Density of Lithium-Metal Batteries.

Adv Mater 2020 Feb 29;32(6):e1906221. Epub 2019 Nov 29.

School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510640, China.

Ceramic oxide electrolytes are outstanding due to their excellent thermostability, wide electrochemical stable windows, superior Li-ion conductivity, and high elastic modulus compared to other electrolytes. To achieve high energy density, all-solid-state batteries require thin solid-state electrolytes that are dozens of micrometers thick due to the high density of ceramic electrolytes. Perovskite-type Li La TiO (LLTO) freestanding ceramic electrolyte film with a thickness of 25 µm is prepared by tape-casting. Compared to a thick electrolyte (>200 µm) obtained by cold-pressing, the total Li ionic conductivity of this LLTO film improves from 9.6 × 10 to 2.0 × 10 S cm . In addition, the LLTO film with a thickness of 25 µm exhibits a flexural strength of 264 MPa. An all-solid-state Li-metal battery assembled with a 41 µm thick LLTO exhibits an initial discharge capacity of 145 mAh g and a high capacity retention ratio of 86.2% after 50 cycles. Reducing the thickness of oxide ceramic electrolytes is crucial to reduce the resistance of electrolytes and improve the energy density of Li-metal batteries.
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http://dx.doi.org/10.1002/adma.201906221DOI Listing
February 2020

Effects of copper on oxidative stress and autophagy in hypothalamus of broilers.

Ecotoxicol Environ Saf 2019 Dec 26;185:109710. Epub 2019 Sep 26.

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

The purpose of this research was to discuss the effects of copper (Cu)-induced toxicity on oxidative stress and autophagy in hypothalamus of broilers. In this study, 240 one-day-old broilers were randomly divided into 4 groups and the contents of dietary Cu in 4 groups were 11 mg/kg (control group), 110 mg/kg (group I), 220 mg/kg (group II), and 330 mg/kg (group III). The experiment lasted for 49 days and the hypothalamus tissues were collected for histological observation and detection of Cu content. Additionally, the indicators related to oxidative stress in hypothalamus were determined. Moreover, the mRNA expression levels of autophagy-related genes and the protein expression levels of Beclin1, LC3-II/LC3-I, and p62 in hypothalamus were measured. Results showed that the treated groups were observed vacuolar degeneration in hypothalamus compared to control group, and the Cu content in hypothalamus was increased with the increase of dietary Cu. Furthermore, the activities of SOD, CAT, T-AOC were increased in group I and group II and then decreased in group III, and the content of MDA and the mRNA levels of Nrf2, HO-1, SOD-1, CAT, GCLC, GCLM, and GST in treated groups were elevated compared to control group. Moreover, the mRNA expression levels of Beclin1, Atg5, LC3-I, LC3-II and the protein expression levels of Beclin1 and LC3-II/LC3-I up-regulated significantly with the increasing levels of Cu. However, the mRNA expression levels of p62 and mTOR and the protein expression level of p62 down-regulated remarkably. Taken together, our present study evidenced that excessive intake of Cu could induce oxidative stress and autophagy in hypothalamus of broilers.
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http://dx.doi.org/10.1016/j.ecoenv.2019.109710DOI Listing
December 2019

Inhibition of Caspase-1-dependent pyroptosis attenuates copper-induced apoptosis in chicken hepatocytes.

Ecotoxicol Environ Saf 2019 Jun 26;174:110-119. Epub 2019 Feb 26.

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

The purpose of this study was to investigate the effects of copper (Cu) on hepatocyte pyroptosis and the relationship between pyroptosis and apoptosis in the mechanisms of Cu toxicity. Primary chicken hepatocytes were cultured in different concentrations of Cu sulfate (CuSO) (0, 10, 50, and 100 μM), N-acetylcysteine (NAC) (1 mM), and Z-YVAD-fluoromethylketone (Z-YVAD-FMK) (10 μM) for 24 h, and the combination of Cu and NAC or Z-YVAD-FMK for 24 h. Cellular morphology and function, cell viability, mitochondria membrane potential (MMP), apoptosis rate, mRNA expression of pyroptosis-related and apoptosis-related genes, and Caspase-1, Caspase-3 proteins expression were determined. These results indicated that Cu markedly induced the mRNA expression of pyroptosis-related genes (Caspase-1, IL-1β, IL-18, and NLRP3) and Caspase-1 protein expression. Furthermore, contents of Caspase-1, IL-1β, and IL-18 in the supernatant fluid of culture hepatocytes were significantly increased in hepatocytes. NAC relieved excess Cu-caused the changes of above genes and proteins. Additionally, Z-YVAD-FMK, caspase-1 inhibitor, which attenuated Cu-induced the increased lactic dehydrogenase (LDH), aspartate amino transferase (AST), alanine aminotransferase (ALT) activities. Furthermore, treatment with Cu and Z-YVAD-FMK could down-regulate the mRNA levels of Caspase-3, Bak1, Bax, and CytC and Caspase-3 protein expression, up-regulate the mRNA expression of Bcl2, increase the MMP and reduce cell apoptosis compared to treatment with Cu in hepatocytes. Collectively, these finding evidenced that excess Cu induced pyroptosis by generating ROS in hepatocytes, and the inhibition of Caspase-1-dependent pyroptosis might attenuate Cu-induced apoptosis.
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http://dx.doi.org/10.1016/j.ecoenv.2019.02.069DOI Listing
June 2019

Copper induces oxidative stress and apoptosis through mitochondria-mediated pathway in chicken hepatocytes.

Toxicol In Vitro 2019 Feb 30;54:310-316. Epub 2018 Oct 30.

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

The aim of this study was to investigate the effects of excessive copper (Cu)-induced cytotoxicity on oxidative stress and mitochondrial apoptosis in chicken hepatocytes. Chicken hepatocytes were cultured in medium in the absence and presence of copper sulfate (CuSO) (10, 50, 100 μM), in N-acetyl-L-cysteine (NAC) (1 mM), and the combination of CuSO and NAC for 24 h. Morphologic observation and function, reactive oxygen species (ROS) level, antioxidant indices, nitric oxide (NO) content, mitochondrial membrane potential (MMP), and apoptosis-related mRNA and protein levels were determined. These results indicated that excessive Cu could induce release of intracellular lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT); increase levels of ROS, superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), lipid peroxidation (LPO), and NO; decrease glutathione (GSH) content and MMP; upregulated Bak1, Bax, CytC, and Caspase3 mRNA and protein expression, inhibited Bcl2 mRNA and protein expression, and induced cell apoptosis in a dose effect. The Cu-caused changes of all above factors were alleviated by treatment with NAC. These results suggested that excessive Cu could induce oxidative stress and apoptosis via mitochondrial pathway in chicken hepatocytes.
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http://dx.doi.org/10.1016/j.tiv.2018.10.017DOI Listing
February 2019

Autophagy attenuates copper-induced mitochondrial dysfunction by regulating oxidative stress in chicken hepatocytes.

Chemosphere 2018 Aug 29;204:36-43. Epub 2018 Mar 29.

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

Copper (Cu) is an essential trace element that is required for the catalysis of several cellular enzymes. Excessive Cu could induce hepatotoxicity in humans and multiple animals. The purpose of this study was to investigate the effects of autophagy machinery on Cu-induced hepatotoxicity. Chicken hepatocytes were cultured in medium in the absence and presence of Cu sulfate (CuSO) (0, 10, 50, and 100 μM) for 0, 6, 12, and 24 h, and in the combination of CuSO and N-acetyl-l-cysteine (NAC) (1 mM), rapamycin (10 nM), and 3-methyladenine (3-MA) (5 mM) for 24 h. Results showed that Cu could markedly increase the number of autophagosomes and LC3 puncta, induce autophagy-related genes (Beclin1, ATG5, LC3Ⅰ, LC3Ⅱ, mTOR, and Dynein) mRNA expression and proteins (BECN1, LC3Ⅱ/LC3Ⅰ) expression. NAC could relieve Cu-induced the changes of above genes and proteins. Additionally, rapamycin attenuated Cu-induced the increased lactic dehydrogenase (LDH), aspartate amino transferase (AST), and alanine aminotransferase (ALT) activities, and SOD-1 mRNA expression as well as the decreased cell viability, reactive oxygen species (ROS), hydrogen peroxide, total superoxide dismutase (T-SOD), malonaldehyde (MDA), catalase (CAT), HO-1 mRNA expression, adenosine triphosphate (ATP) levels, mitochondrial mass, and mitochondria membrane potential (MMP). But 3-MA had the opposite effects on above factors. Collectively, these findings provide strong evidence that Cu could induce autophagy by generating excessive ROS in hepatocytes, and autophagy might attenuate Cu-induced mitochondrial dysfunction by regulating oxidative stress.
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http://dx.doi.org/10.1016/j.chemosphere.2018.03.192DOI Listing
August 2018