Administration Of Copper Sulfate Research Articles

Effect of Copper sulphate pollution and its antidote penicillamine on serum and brain tissues markers of albino rats

seventy albino rats were divided into seven equal groups each containing 10 rats (G1:control received distilled water) ; (G2: 0.1 LD50 of CuSO4) ; (G3: 0.2 LD50 of CuSO4) ; (G4: 0.4 LD50 of CuSO4) ; (G5: 0.1 LD50 of CuSO4 +100mg/kg/day of penicillamine) ; (G6: LD50 of CuSO4.+100 mg/kg/day of penicillamine) and (G7: LD50 of CuSO4+ 100 mg /kg/day of penicillamine) for 30 days and at the end of the experiment all rats were sacrificed and blood samples and brain tissues were collected for biochemical assaying of Fasting Blood Glucose (FBG), Serum Cu level, serum tyrosinase activity, oxidative stress marker Malondialdehyde (MDA) and Total Antioxidant Activity (TAC). also, DNA determination of relative gene expression of cerebral Adenosine monophosphate-activated Protein Kinase (AmpK), Protein Kinase (AKT), Phosphatidylinositol-3-Kinase (PI3K), Cytochrome c oxidase (Cyto co ), and Glucose -6- Phosphate Dehydrogenase (G6PD). Results: The result showed that administration of copper sulphate with different levels induced a significant increase in fasting blood glucose level, lipid peroxidation marker MDA, serum copper level, and serum tyrosinase activity, and a significant decrease in TAC. Moreover, copper sulphate administration elicited a significant downregulation ( AmpK, AKT, PI3K, Cytochrome c oxidase, G6PD).it could be approved that penicillamine could abolish the negative impact of copper sulphate on neural tissues and serum enzymes. Conclusion: D-penicillamine can reduce neurotoxicity and oxidative stress caused by copper pollution.

The protective effect of betanin and copper on spinal cord ischemia–reperfusion injury

Context: Both copper and betanin have been implicated as having significant bioactivity against ischemic damage in a variety of experimental and clinical settings. The aim of this study is to investigate whether betanin and copper have any protective effect on spinal cord in an ischemia–reperfusion (I/R) model in rats. Design: Spraque-Dawley rats were used in four groups: Sham group (n = 7), control group (laparotomy and cross-clamping of aorta, n = 7), betanin treatment group (dosage of 100 mg/kg of betanin administered intraperitoneally (i.p.) 60 min before laparotomy, n = 7), copper sulfate treatment group (administered copper sulfate i.p. at a dose of 0.1 mg/kg/day for 7 days before laparotomy, n = 7). Malondialdehyde (MDA), glutathione (GSH) levels, myeloperoxidase (MPO) and superoxide dismutase (SOD) activity were measured. Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay was also performed to evaluate apoptosis. Setting: Kafkas University, Faculty of Medicine, Kars, Turkey. Results: I/R injury was successfully demonstrated with the surgical model. Betanin and copper treatment significantly decreased MDA levels, MPO activity and the number of apoptotic cells in the spinal cord. Betanin and copper treatment significantly increased GSH levels. Copper treatment significantly increased SOD activity, whereas betanin was not as effective. Apoptotic cells were significantly decreased in both treatment groups. Conclusion: I/R injury of the spinal cord can be successfully demonstrated by aortic clamping in this surgical model. Betanin/Copper sulphate has ameliorative effects against operative I/R injury. Low toxicity of those agents makes them ideal targets for clinical research for this purpose.

Antioxidant and hepatoprotective effects of vitamin E and melatonin against copper-induced toxicity in rats

Purpose: To determine the preventive effects of vitamin E and melatonin against acute copper toxicity in rats.Methods: A total of 28 Wistar albino rats were randomly divided into four equal groups: control, copper sulfate, copper sulfate + vitamin E, and copper sulfate + melatonin. The following were analyzed in all groups: serum enzymes; activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), protein carbonyl (PC) content. Liver histopathology was also evaluated.Results: PC levels decreased in rats administered copper sulfate/vitamin E and copper sulfate/melatonin. The activities of SOD, GPx and CAT increased significantly with melatonin and vitamin E administration when compared with administration of copper sulfate alone. Histopathologic features revealed severe degeneration and necrotic changes in rats administered copper sulfate alone. These changes were observed to a lesser extent in the copper sulfate + melatonin group and only minimally in the copper sulfate + vitamin E group.Conclusion: Vitamin E and melatonin are protective against liver damage caused by copper. Vitamin E, and melatonin may strengthen the antioxidant defense system by inhibiting protein oxidation and enhancing the activity of antioxidant enzymes.Keywords: Copper, Melatonin, Vitamin E, Protein oxidation, Hepatoprotective

Copper (II) and/or arsenite-induced oxidative stress cascades apoptosis and autophagy in the skeletal muscles of chicken

Arsenic (As) is a ubiquitous environmental toxin and robust inducer of oxidative stress (OxS). Copper (Cu) is an essential microelement, which participates in OxS as a cofactor for certain enzymes, with narrow optimal range between essential and toxic concentrations. However, their effects are rarely studied in chicken skeletal muscles, which have soaring per capita consumption andare susceptible to oxidative damage. In the present study, we demonstrated that the administration of copper sulfate (300 mg kg−1) or arsenite (30 mg kg−1) individually or their co-administration leads to varying degrees of OxS in the skeletal muscles of chickens. Corresponding to the protein expression pattern, the mRNA levels of caspase, B-cell lymphoma-2 (Bcl-2) families, and autophagy-related genes were also compromised in the experimental groups, indicating the involvement of both apoptotic and autophagic cell death. Additionally, rampant mitochondrial fission caused the vicious cycle between imbalanced mitochondrial dynamics and OxS, thus tethering intracellular homeostasis. The abovementioned muscle damage and index anomalies were time dependent, and more deteriorated effects were observed in Cu2+ and arsenite co-administered groups than those in groups administered Cu2+ and arsenite alone. Intriguingly, in the studied skeletal muscles, namely wing biceps brachii and leg gastrocnemius, there were conspicuous differences in oxidative toxicity susceptibility, which needs further study. The present study showed that Cu and/or As induce oxidative damage in chicken skeletal muscles and discussed its mechanism in terms of apoptosis, autophagy, and mitochondrial dynamics, thus voicing concerns about poultry breeding areas cross-contaminated with Cu2+ and arsenite.

TESTICULO-PROTECTIVE EFFECT OF MORINGAOLEIFERA SEED EXTRACT ON COPPER SULPHATE INDUCED INJURY IN WISTAR RATS

The aim of this study was to observe the testiculo-protective effect of aqueous extract of Moringaoleifera seed also known as Moringa seed on copper sulphate induced injury in Wistar rats. Twenty adult male Wistar rats (200-300g) were randomly selected into four groups (5 rats per group). Group A served as control group and were given 2ml/kg of distilled water. Group B was administered aqueous extract of Moringa seed only (200mg/kg body weight). Group C was administered aqueous extract of Moringa seed (200mg/kg body weight) and copper sulphate (100mg/kg body weight) concurrently. Group D was administered copper sulphate only (100mg/ kg body weight). All administrations lasted for three weeks. Results showed that in group D, there was proliferation of interstitial cells, degeneration of the seminiferous tubules as evidenced by hyalinization and blockage of the tubular lumen by immature spermatogenic series due to an arrest of spermatogenesis. There was also a significant decrease in testosterone level anda significant increase in lactate dehydrogenase level when compared with the control at p< 0.05. In group C rats, the results show mild interstitial connective tissue loosening and normal sequential maturation of spermatogenic series and normal levels of testosterone and lactate dehydrogenase. Conclusively, administration of copper sulphate causes testicular damage as evidenced by testicular hyalinization and arrest of spermatogenesis. However concurrent treatment of the rats with Moringa oleifera seed extract and copper sulphate have no effect on the testes, establishing the fact that Moringa oleifera seed extract offers a protective effect to the testes. Keywords: Testosterone; Moringa; copper sulphate; wistar rat; Moringa oleifera

A Study on the Effects of Orally Administered Copper Sulfate on Learning and Spatial Memory of Wistar Rats

A Study on the Effects of Orally Administered Copper Sulfate on Learning ‎and Spatial Memory of Wistar Rats Author(s): M Palizvan , A Jand, Y Jand , M Taherinejad Abstract: BACKGROUND AND OBJECTIVE: Copper is one of the main micronutrients in the human body. Malfunction in copper homeostasis results in Menkes syndrome and Wilson’s disease, which are associated with complications such as seizure and impairments in learning and memory. Use of high copper concentrations can cause permanent damage to the cells and neurons. The aim of this study was to examine the toxic effects of orally administered copper sulfate on rats’ learning in Morris water maze. METHODS: In this experimental study, 39 Wistar rats were divided into male (n=21) and female (n=18) groups. These two groups were each randomly divided into three sub-groups. The control group received distilled water, while the other two groups were administrated 1 and 1.5 mM of copper sulfate, dissolved in distilled water for a period of one month. After this period, the Morris water maze was incorporated to evaluate the spatial memory of rats. FINDINGS: In male rats, copper sulfate, which was added to drinking water, made no significant changes in the distance traveled to find the platform (24.09%±3.01 in the control group, 26.06%±2.95 in the 1 mm copper sulfate group, and 25.68%±1.82 in the 1.5 mM copper sulfate group), the time spent to find the platform (23.93±2.87 in the control group, 25.54±3.47 in the 1 mM copper sulfate group, and 25.33±1.92 in the 1.5 mM copper sulfate group), or the swimming speed. The comparison of female groups showed that 1 and 1.5 mM concentrations of copper sulfate could not cause any significant impairments in learning of rats. CONCLUSION: The results showed that the addition of copper sulfate to drinking water have no detrimental impacts on the memory or learning of male and female rats. Keywords: Copper Sulfate, Spatial Learning, Morris Water Maze, Rats,

Histopathological evaluation of supportive effects of Rosa damascene on mice testes, following long term administration of copper sulfate

Abstract Objective To evaluate the supportive effects of Rosa damascene (R. damascene) essential oil on epididymal sperm quality and histopathology of testes following long term administration of copper sulfate in mice. Materials and methods The study comprised of four different groups of six mice as follows: group Cu, which received 0.1 mL copper sulfate solution at dose of 100 mg/kg, group R which received 0.1 mL R. damascene essential oil at dose of 1 mg/kg, treatment group (T) which received copper sulfate solution (100 mg/kg) and treated by R. damascene essential oil (1 mg/kg), and control group (C) which received the same volume of normal saline. The supplements were gavaged in all animals every other day, during experimental period. All animals of each experimental group were sacrificed 42 days after the beginning of experiment. Results Results showed that sperm concentration, motility and viability in group Cu were significantly decreased after 6 weeks, and severe degenerative changes were observed in testicular tissues in comparison with the control group. In treatment group, significant improve in the sperm count, motility and viability, and normal architecture in most seminiferous tubules with organized epithelium was observed compared to the group Cu. Conclusions Administration of the essential oil of R. damascene owning to its antioxidant properties is able to protect the testis and epididymal sperm from the adverse effects of copper poisoning in mice.

Supportive effects of Rosa damascene essential oil on epididymal sperm quality following long-term administration of copper sulfate in mice

Supportive effects of Rosa damascene essential oil on epididymal sperm quality following long-term administration of copper sulfate in mice

Responses of neurons in the caudal medullary lateral tegmental field to visceral inputs and vestibular stimulation in vertical planes

The dorsolateral reticular formation of the caudal medulla, or lateral tegmental field (LTF), has been classified as the brain's “vomiting center” as well as an important region in regulating blood pressure. We examined in cats the responses of LTF neurons to rotations of the body that activate vertical semicircular canals and otolith organs, as well as to stimulation of baroreceptors and gastrointestinal receptors (through the intragastric administration of the emetic compound copper sulfate). Half of the LTF neurons exhibited graviceptive responses to vestibular stimulation, similar to primary afferents innervating otolith organs. The other half of the neurons had complex responses, suggesting that they received convergent inputs from a variety of vestibular receptors, as expected for neurons that contribute to the generation of motion sickness. The administration of copper sulfate often modulated the gain of responses of LTF neurons to vestibular stimulation, particularly for units whose spontaneous firing rate was altered by infusion of drug (median of 459%). The present results thus raise the prospect that emetic signals from the gastrointestinal tract modify the processing of vestibular inputs by LTF neurons, thereby affecting the probability that vomiting will occur as a consequence of motion sickness.

Histopathological evaluation of supportive effect of vitamin C on testes following long-term administration of copper sulfate in mice

This study was set to investigate whether the adverse effects of long-term copper (Cu) consumption on testicular tissue could be prevented by vitamin C administration. Thirty-six sexually mature male NMRI mice were randomly divided into three groups of 12 animals. The first group (group Cu) which is treated by gavage with copper sulfate at a dose of 200 mg/kg/day (0.2 ml) and 0.1 ml of distilled water via intraperitoneal (i.p.) injection daily for 6 weeks, the treatment group (group Cu + Vit.C) which is treated by gavage with copper sulfate at a dose of 200 mg/kg/day (0.2 ml) and received 10 mg/kg/day (0.1 ml) vitamin C by i.p. injection, and the control group which received the same volume of distilled water by gavage and i.p. injection during the experimental period. Shrinkage and collapse of tubules, decreased number of germinal cells and decrease in epithelial height were histopathologial lesions of testes of Cu group, while, treatment group showed normal morphology with presence of spermatozoa in their lumen. In conclusion, vitamin C can be one of the suitable choices for preventive therapeutic effects and/or improvement in testicular tissue after Cu toxicosis.

Responses of neurons in the caudal medullary lateral tegmental field to visceral inputs and vestibular stimulation in vertical planes.

The dorsolateral reticular formation of the caudal medulla, or the lateral tegmental field (LTF), has been classified as the brain's "vomiting center", as well as an important region in regulating sympathetic outflow. We examined the responses of LTF neurons in cats to rotations of the body that activate vestibular receptors, as well as to stimulation of baroreceptors (through mechanical stretch of the carotid sinus) and gastrointestinal receptors (through the intragastric administration of the emetic compound copper sulfate). Approximately half of the LTF neurons exhibited graviceptive responses to vestibular stimulation, similar to primary afferents innervating otolith organs. The other half of the neurons had complex responses, including spatiotemporal convergence behavior, suggesting that they received convergent inputs from a variety of vestibular receptors. Neurons that received gastrointestinal and baroreceptor inputs had similar complex responses to vestibular stimulation; such responses are expected for neurons that contribute to the generation of motion sickness. LTF units with convergent baroreceptor and vestibular inputs may participate in producing the cardiovascular system components of motion sickness, such as the changes in skin blood flow that result in pallor. The administration of copper sulfate often modulated the gain of responses of LTF neurons to vestibular stimulation, particularly for units whose spontaneous firing rate was altered by infusion of drug (median of 459%). The present results raise the prospect that emetic signals from the gastrointestinal tract modify the processing of vestibular inputs by LTF neurons, thereby affecting the probability that vomiting will occur as a consequence of motion sickness.

Clinicopathological Analysis of Hematological Disorders in Tube-Fed Patients with Copper Deficiency

Anemia and leukopenia caused by copper deficiency are well-documented consequences of long-term total parenteral nutrition. We measured the serum copper levels of bed-ridden patients receiving enteral feeding, and evaluated optical and ultrastructural features of bone marrow before and after copper supplementation. Serum samples were obtained from 15 bed-ridden elderly patients receiving tube feeding (TF) and 10 age-matched bed-ridden patients who took food orally (CO), and the copper ceruloplasmin concentration of each sample was measured. Bone marrow samples were obtained from patients who exhibited copper deficiency and leukopenia and/or anemia before and after the copper supplementation, for use in light and electron microscopic analysis. The tube-fed patients had significantly lower mean serum copper and ceruloplasmin concentrations than the control patients. Seven of the 15 tube-fed patients had reduced serum copper concentrations and leukopenia. Six of those 7 patients also had anemia. Copper sulfate was administered to those 7 patients by enteral tube; their copper concentration, anemia and leukopenia improved within 1 month after they were administered copper sulfate. In the bone marrow examination before copper supplementation, light microscopy showed cytoplasmic vacuolization in both myeloid and erythroid precursors, and electron microscopy showed electron-dense deposits in mitochondria and cytoplasm of erythroid and myeloid cells. After copper supplementation, these pathological changes disappeared. Bicytopenia is likely to occur in tube-fed patients with copper deficiency. Copper deficiency appears to be associated with cytoplasmic vacuolization and electron-dense deposits in mitochondria in erythroid and myeloid cells.

Effects of Copper on Bone Component in the Femoral Tissues of Rats: Anabolic Effect of Zinc Is Weakened by Copper

The effects of copper on biochemical components in the femoral-diaphyseal (cortical bone) and -metaphyseal (trabecullar bone) tissues of rats in vivo and in vitro were investigated. Rats were orally administered copper sulfate (50, 100, or 200 microg Cu/100 g body weight) once daily for 7 d. Calcium content in the diaphyseal and metaphyseal tissues was significantly decreased with the administration of copper (200 microg/100 g), while alkaline phosphatase activity in these tissues was not significantly changed by copper administration. The diaphyseal DNA content was significantly decreased with the administration of copper (50, 100, or 200 microg/100 g). Moreover, the femoral-diaphyseal and -metaphyseal tissues were cultured for 48 h in serum-free medium containing either vehicle or copper (10(-7) - 10(-4) M). Culture with copper (10(-7) - 10(-4) M) caused a significant decrease in alkaline phosphatase activity in the diaphyseal and metaphyseal tissues, while calcium and DNA contents in these tissues were not significantly changed. Culture with parathyroid hormone [PTH (1-34); 10(-7) M], a bone-resorbing factor, caused a significant decrease in calcium content in the diaphyseal and metaphyseal tissues. This decrease was completely inhibited in the presence of copper (10(-6) or 10(-5) M). Culture with zinc sulfate (10(-4) M) caused a significant increase in calcium content and alkaline phosphatase activity in the diaphyseal and metaphyseal tissues. The effects of zinc (10(-4) M) in increasing femoral calcium content and alkaline phosphatase activity were not seen in the presence of cycloheximide (10(-6) M), an inhibitor of protein synthesis, suggesting that the effects of zinc are involved in newly synthesized protein components. The effects of zinc in increasing calcium content and alkaline phosphatase activity in the diaphyseal and metaphyseal tissues were significantly weakened in the presence of copper (10(-4) M). The inhibitory effects of copper were further enhanced in the presence of cycloheximide. This study demonstrates that supplementation with copper in adequate copper nutrition does not have anabolic effects on bone components in vivo and in vitro and that copper weakens the anabolic effects of zinc in vitro.

Effect of copper sulfate on experimental atherosclerosis.

Serum copper concentration increases significantly (p < 0.01) in rats with experimental atherosclerosis compared to a control group. The serum zinc, the zinc, and copper concentration in abdominal aorta and in liver decreases significantly (p < 0.05) compared to the control group. Administration of copper sulfate for 100 d in these animals induces a significant increase of serum copper (p < 0.01), decrease of serum cholesterol (p < 0.05) and increase of liver copper concentration as compared with the group fed only a high cholesterol diet. In the aorta of these animals the copper concentration increases and edema and lipid infiltration are considerably less than in the group of animals fed only a high lipid diet.

Sibling cases of a degenerative neurological disease associated with hypocupraemia and hypobetalipoproteinaemia

We describe two siblings, a boy and his younger sister, with degenerative neurological disturbances, hypocupraemia and hypobetalipoproteinaemia. The neurological features in both cases were developmental delay, dysarthria, hyperkinetics with an attention deficit, dysdiadochokinesis, night blindness, myoclonic jerks and convulsions. Their serum cooper levels did not increase despite administration of copper sulphate both orally or intravenously. The copper contents of the cultured fibroblasts in the patients were 1.5-fold that of controls. Although neurological disorders associated with abnormal copper metabolism and inherited in an X-linked manner have been previously reported, this is the first report of a neurodegenerative disease concurrent with abnormal copper metabolism and hypobetalipoproteinaemia.

Vestibular, central and gastral triggering of emesis. A study on individual susceptibility in rats.

Using kaolin intake as a behavioral index of emesis in rats, we examined the relationship between susceptibility to motion sickness and to emesis induced by apomorphine or copper sulfate. Rats showed a wide variation in susceptibility to motion sickness. Significant positive correlations were found between susceptibility to motion sickness and to emesis induced by intraperitoneal administration of apomorphine and by oral administration of copper sulfate. Motion, apomorphine and copper sulfate induce emesis through different receptors, so these findings suggest that the sensitivity of a common locus of emesis, presumably the emetic center in the brain stem, is one determinant of individual differences in susceptibility to motion sickness.

Experimental hypercupremia does not result in increases in copper in lens, iris, or ocular fluids.

Rabbits were continuously administered copper sulfate via subcutaneously implanted osmotic pumps. After one month, plasma, liver, ocular tissues and fluids were analyzed for copper by atomic absorption spectrophotometry. No elevation in copper content of the ocular fluids, lens or iris was noted although, dose-related increases were seen in the plasma and liver indicating that the copper was absorbed and disseminated systemically. It is likely that excess copper, like that which is normally ingested and absorbed, is largely protein-bound in the circulation, preventing crossing of the blood-ocular barrier.

Intragastric copper sulfate produces a more reliable conditioned taste aversion in vagotomized rats than in intact rats

Although copper sulfate is an emetic stimulus, preliminary experiments failed to obtain a taste aversion in intact rats following intragastric administration as had been previously reported in the literature. Several experiments were therefore run to further investigate the capacity of intragastric copper sulfate to function as an unconditioned stimulus for taste aversion learning and the role of the vagus in mediating that learning. The results of the first series of experiments showed that intragastric administration of copper sulfate (5 mg/kg X 5H2O) was more effective in reliably producing a taste aversion in vagotomized rats than in sham-operated control rats. The second experiment examined the effects of area postrema lesions on the acquisition of a taste aversion produced by intragastrically administered copper sulfate in vagotomized rats. The results indicated that the taste aversion observed following treatment with intragastric copper sulfate in vagotomized rats could be prevented by lesions of the area postrema. The present results indicate that intragastric administration of copper sulfate is a more reliable unconditioned stimulus for taste aversion learning in vagotomized rats than in intact rats. It is not certain what factors might account for the discrepant results between the present experiments and previously published research.

The effects of divalent ions on morphine analgesia and abstinence syndrome in morphine-tolerant and-dependent mice

Intracerebral administration of copper sulfate potentiated morphine analgesia in morphine-tolerant and -dependent mice, but copper failed to affect other abstinence signs. When abstinence was precipitated with a partial antagonist, nalorphine, stereotyped jumping was not inhibited by either calcium or copper. These modifications of narcotic effects by copper were produced without alterations in the brain disposition of morphine. Total radioactivity in the brain following radioactive naloxone administration was also not altered.

Hypocuprosis: The effects of administration of copper sulphate to cattle through the water supply

Abstract Extract Hypocuprosis in Northland† as it pertains to cattle has been previously discussed by Smith and Coup (1972) and Smith (1975).