Effect of Copper Toxicity on Lymphoid Organs in Ducklings

one-day-old Tianfu meat ducklings were divided into three groups, and fed on dietsas follows:(1)control (Cu 12.16 mg kg-1),(2) copper toxicⅠ(Cu 850 mg kg-1) and (3)copper toxicⅡ( Cu 1050 mg kg-1) for studies on effects of copper toxicity on lymphoidorgans in duckling with the methods of experimental pathology and flow cytometry (FCM).The weight and growth index of the thymus, spleen and bursa of Fabricius were markedlyreduced (P<0.05 or P<0.01) in both copper toxic groupⅠand Cu toxic group Ⅱ whencompared with control group. The G0/G1 phase of the cell cycle of the thymus, spleen andbursa of Fabricius was much higher, and S, G2+M phases lower in Cu toxic groupsⅠand Ⅱthan in the control group. There were lymphocyte degeneration and depletion of lymphoidorgans, and the reticular cells of spleen and bursa of Fabricius proliferated and thereticular cells of thymus were also degenerate and necrotic in Cu toxic groups. Theresults demonstrated that Cu toxicity seriously impaired the progression of lymphocytesfrom the G0/G1 phase to S phase, inhibited the development of lymphoid organs and causedmarked pathological injury in lymphoid organs. The results also showed that the effectof Cu toxicity on the primary lymphoid organs occurred stronger than on the secondarylymphoid organs. The effect of Cu toxicity was the greatest on the bursa of Fabricius,followed by the thymus, and then the spleen. Potential mechanisms underlying aforementionedobservation were also discussed.

Effect of Copper Toxicity on Lymphoid Organs in Broilers

The experiment was conducted to examine the effect of copper toxicity on lymphoid organs by experimental pathology andflow cytometry (FCM). 180 one-day-old Avian broilers were divided into three groups, and fed diets as follows: 1) Control(Cu 11.97 mg kg-1 diet), 2) Cu- toxic groupⅠ(Cu 650 mg kg-1) and 3) Cu- toxic groupⅡ(Cu 850 mg kg-1) for six weeks.Compared with the control, the growth index of the thymus, spleen and bursa of Fabricius were markedly reduced (P<0.05or P<0.01), the G0/G1 phase of cell cycles of the thymus, spleen and bursa of Fabricius was higher (P<0.05 or P<0.01), whilethe S phase and proliferating index were lower (P<0.05 or P<0.01) in both Cu-toxic group Ⅰ and Cu-toxic group Ⅱ. Theresults demonstrated that Cu toxicity seriously impaired the progression of lymphocytes from the G0/G1 phase to the Sphase, inhibited the growth and development of lymphoid organs.

Alleviation of Copper Toxicity to Maize by Phosphorus Fertilizer in Purple Soil

A pot experiment was conducted to evaluate the effects of phosphorus fertilizer in inhibiting the copper toxicity to maize(Zea mays L.) in neutral purple soil. Results indicated that the growth of the shoot and roots of maize plant was obviously reduced by copper and the height and biomass were significantly negatively correlated to the application levels of copper (r=-0.899**^-0.994**) at no P and low P (100 mg kg-1).However, the maize biomass was relatively increased and the high Cu (100 and 200 mg kg-1) induced toxicity of maize was greatly alleviated in all treatments with medium P (300 mg kg-1) and high P (500 mg kg-1).To maintain the normal growth of maize plant (≥3.68 g pot-1), the critical application rates of phosphorus fertilizer should be 160, 210, 300 and 500 mg P kg-1 at 10, 50, 100 and 200 mg Cu kg-1 levels of the soil,respectively. The increases in polyphenol oxidase and catalase activities in maize leaf and dehydrogenase activity in roots by phosphorus fertilizer were in the order of medium p>high p>low p>no P. Activities of polyphenol oxidase and catalase were significantly positively correlated to the application levels of copper (r=0.892**~0.924**), whereas that of dehydrogenase was just reverse (r=-0.966**) at no P. Medium and high P repressed the influence of copper on activities of three enzymes. Phosphorus fertilizer reduced the copper concentrations of maize roots and leaf and the change ranges of the P/Cu ratio of maize roots and the P/Cu, N/Cu and K/Cu ratios of maize leaf. The three ratios of maize leaf were 256±71.5, 2643±839 and 1133±440 at normal growth of maize plant, respectively. Soil available Cu could be markedly cut down by application of phosphorus fertilizer, especiallly at high phosphorus level.

Science Letters:Gama-aminobiityric acid accumulation in Elsholtzia splendens in response to copper toxicity

A solution with different Cu supply levels was cultured to investigate gama-aminobutyric acid (GABA) accumulation in Elsholtzia splendens, a native Chinese Cu-tolerant and accumulating plant species. Increasing Cu from 0.25 to 500 ?mol/L significantly enhanced levels of GABA and histidine (His), but considerably decreased levels of aspartate (Asp) and glutamate (Glu) in the leaves. The leaf Asp level negatively correlated with leaf Cu level, while leaf GABA level positively correlated with leaf Cu level. The leaf Glu level negatively correlated with leaf GABA level in Elsholtzia splendens. The depletion of leaf Glu may be related to the enhanced synthesis ofleafGABA under Cu stress.

Copper homeostasis and neurodegenerative diseases

Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of concentrations.Copper homeostasis is meticulously maintained through a complex network of copper-dependent proteins,including copper transporters(CTR1 and CTR2),the two copper ion transporters the Cu-transporting ATPase 1(ATP7A)and Cu-transporting beta(ATP7B),and the three copper chaperones ATOX1,CCS,and COX17.Disruptions in copper homeostasis can lead to either the deficiency or accumulation of copper in brain tissue.Emerging evidence suggests that abnormal copper metabolism or copper binding to various proteins,including ceruloplasmin and metallothionein,is involved in the pathogenesis of neurodegenerative disorders.However,the exact mechanisms underlying these processes are not known.Copper is a potent oxidant that increases reactive oxygen species production and promotes oxidative stress.Elevated reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial dysfunction.Reactive oxygen species serve as key signaling molecules in copper-induced neuroinflammation,with elevated levels activating several critical inflammatory pathways.Additionally,copper can bind aberrantly to several neuronal proteins,including alphasynuclein,tau,superoxide dismutase 1,and huntingtin,thereby inducing neurotoxicity and ultimately cell death.This study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases,with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease pathogenesis.By synthesizing the current findings on the functions of copper in oxidative stress,neuroinflammation,mitochondrial dysfunction,and protein misfolding,we aim to elucidate the mechanisms by which copper contributes to a wide range of hereditary and neuronal disorders,such as Wilson's disease,Menkes'disease,Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,Huntington's disease,and multiple sclerosis.Potential clinically significant therapeutic targets,including superoxide dismutase 1,D-penicillamine,and 5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline,along with their associated therapeutic agents,are further discussed.Ultimately,we collate evidence that copper homeostasis may function in the underlying etiology of several neurodegenerative diseases and offer novel insights into the potential prevention and treatment of these diseases based on copper homeostasis.

Transcription factor OsWRKY72 is involved in Cu/Cd toxicity by regulating lignin synthesis in rice

Maintenance of ion homeostasis in plant cells is an essential physiological requirement for sustainable growth,development,and yield of crops.Plants respond to high levels of heavy metals such as copper(Cu)and cadmium(Cd)to avoid irreversible damage at the structural,physiological and molecular levels.Our previous study found that rice germin-like proteins(OsGLPs)are a type of Cu-responsive proteins.The deletion of 10 tandem OsGLP genes on chromosome 8 led to more severe heavy metal toxicity in rice.In this study,we show that rice WRKY transcription factor OsWRKY72 negatively regulates OsGLP8-7transcription.Overexpression of OsWRKY72 weakens the Cu/Cd tolerance of rice when exposed to Cu and Cd.OsWRKY72 suppressed expression of OsGLP8-7 and lignin synthesis genes,resulting in reduced lignin polymerization and consequently lower lignin accumulation in cell walls,thereby increasing the Cu and Cd accumulation.In addition,OsWRKY53 bound to OsWRKY72 to alleviate the transcriptional inhibition of OsGLP8-7.These results revealed that OsWRKY72-OsGLP8-7 is an important module response of rice to heavy metal stress,and that transcription factor OsWRKY72 acts upstream of OsGLP8-7 to regulate Cu/Cd toxicity.

Copper Ameliorates Fluoride Toxicity in Fluoride and Molybdenum Fed Rabbits

Hydrofluorosis is a major public health problem in India, which is aggravated by presence or absence of some minerals in water or food. Fluoride by itself or in combination with other elements like molybdenum （Mo） in diet or water changes excretion/retention of bone minerals. Sorghum and pearl millet grown and consumed in fluorosis endemic areas contained significantly higher amounts of Mo than that grown in non-fluorotic areas in India.

Effects of Copper on the Photosynthesis and Oxidative Metabolism of Amaranthus tricolor Seedlings

The objective of the present study was to gain better insight into the physiological mechanisms on the effects of copper （Cu） on photosynthesis and active oxygen metabolism in three-colored amaranth plant （Amaranthus tricolor）. Three- colored amaranth seedlings were subjected to different Cu levels in soils during the entire experimental period. The parameters of growth, photosynthesis, mineral elements contents, and active oxygen metabolism were investigated using plant physiological methods. The results showed that 2.0 and 4.0 mmol Cu kg^-1 treatments decreased the whole plant biomass to 91 and 73% of the control, respectively. The net photosynthetic rate （Pn） and the stomatal conductance （gs） were similarly reduced in the third leaves of three-colored amaranth seedlings treated with 2.0 and 4.0 mmol Cu kg^-1 soil, respectively. None of the investigated Cu levels decreased the internal CO2 concentration （Ci）. The effect of Cu on the potential efficiency of photosystem Ⅱ （Fv/Fm） was negligible, whereas the effect of Cu on the PS Ⅱ quantum efficiency （ΦPS Ⅱ） after plant adaptation in actinic irradiation was more noticeable. On the other hand, decreases in water percentage, contents of photosynthetic pigments and mineral elements including Fe, K, and Mg, and significant increase in the Cu content were observed in the third leaves of Cu-treated plants. Superoxide dismutase （SOD） and peroxidase （POD） activities as well as the proline （Pro） content significantly increased in the third leaves of the three-colored amaranth seedlings treated with 2.0 and 4.0 mmol Cu kg^-1 soil, while catalase （CAT） and ascorbate peroxidase （APX） activities as well as the contents of carotenoid （Car）, glutathione （GSH）, and ascorbic acid （AsA） decreased, and accompanied by the increases in the contents of hydrogen peroxide （H2O2）, superoxide anion （O2^-）, and malondialdehyde （MDA）, and electrolyte leakage. As a result of the imbalance of active oxygen metabolism, Pn and ΦPS Ⅱ decreased, and peroxidization enhanced under levels of 2.0 and 4.0 mmol Cu kg^-1 soil. Finally, the growth of three-colored amaranth plant was significantly inhibited.

Reversible lesions in the brain parenchyma in Wilson's disease confirmed by magnetic resonance imaging:earlier administration of chelating therapy can reduce the damage to the brain

The aim of this study was to evaluate the resolution of brain lesions in patients with Wilson’s disease during the long-term chelating therapy using magnetic resonance imaging and a possible signiifcance of the time latency between the initial symptoms of the disease and the introduction of this therapy. Initial magnetic resonance examination was performed in 37 patients with proven neurological form of Wilson’s disease with cerebellar, parkinsonian and dystonic presentation. Magnetic resonance reexamination was done 5.7 ± 1.3 years later in 14 patients. Patients were divided into： group A, where chelating therapy was initiated 〈 24 months from the ifrst symp-toms and group B, where the therapy started≥ 24 months after the initial symptoms. Symmetry of the lesions was seen in 100% of patients. There was a signiifcant difference between groups A and B regarding complete resolution of brain stem and putaminal lesions （P= 0.005 andP=0.024, respectively）. If the correct diagnosis and adequate treatment are not established less than 24 months after onset of the symptoms, irreversible lesions in the brain parenchyma could be ex-pected. Signal abnormalities on magnetic resonance imaging might therefore, at least in the early stages, represent reversible myelinolisis or cytotoxic edema associated with copper toxicity.