Toxicity Of CuSO4 Research Articles

The Resveratrol Alleviates the Hepatic Toxicity of CuSO4 in the Rat.

Cu is toxic to humans and other animals. Oxidative stress is an important mechanism involved in Cu toxicity. Resveratrol (RSV) is an antioxidative compound, so could counteract Cu toxicity. The aim of this study was to determine whether RSV protects the liver from the effects of CuSO4. Forty male Sprague-Dawley rats (5weeks old, 110-120g) were divided into four groups (n = 10 per group), a control group and groups treated with CuSO4 at a dose of 200mg/kg body weight (BW), RSV at a dose of 15mg/kg BW, and CuSO4 at a dose of 200mg/kg BW and RSV at a dose of 15mg/kg BW. The treatments were orally administered for 30days. The livers were removed from the rats at the end of the study, and the cytochrome P450, cytochrome b5, Cu, Fe, Zn, glutathione peroxidase, superoxide dismutase, reactive oxygen species, aspartate aminotransferase, and alanine aminotransferase concentrations in the livers were determined. CuSO4 decreased the BW, liver weight, and cytochrome P450, cytochrome b5, Fe, Zn, glutathione peroxidase, and superoxide dismutase concentrations but increased the Cu, aspartate aminotransferase, alanine aminotransferase, and reactive oxygen species concentrations relative to the control group. RSV alleviated the toxic effects of CuSO4 on the liver, indicating that RSV attenuates CuSO4-induced liver injury by decreasing the liver transaminase concentration and oxidative stress, promoting antioxidative activity and cytochrome P450 enzymes, and maintaining balance in the trace element concentrations. The results indicate that RSV could be used to treat CuSO4 toxicity.

Liposomal Curcumin Attenuates the Incidence of Oxidative Stress, Inflammation, and DNA Damage Induced by Copper Sulfate in Rat Liver.

Background:Copper is an essential element that is used widely in agriculture as fungicides and insecticides; for example, it is used to control schistosomiasis and as an antiseptic and germicide. Copper sulfate (CuSO4) induces multiorgan dysfunction through the stimulation of reactive oxygen species and oxidative stress. Despite the numerous pharmacological effects of curcumin (CUR), its pharmacokinetic properties are less promising. Hence, there is an urgent need for novel, effective strategies to attenuate heavy metal toxicity and consequently improve the treatment efficiency. Liposomal curcumin (L-CUR) improves the dissolution, stability, and bioavailability of treatment agents. This study compared the efficacy of CUR and L-CUR with that of desferrioxamine (DES), which is a heavy metal chelator against CuSO4 hepatotoxicity.Methods:All treatments with the aforementioned antioxidants were administered for 7 days along with CuSO4. Serum levels of alanine aminotransferase, aspartate transaminase, lactate dehydrogenase, and C-reactive protein, hepatic nitric oxide (NO), and lipid peroxides (malondialdehyde) were measured; protein expression of cyclooxygenase 2 and DNA fragmentation were evaluated. Histopathological examinations were also conducted.Results:A toxic dose of CuSO4 induced elevations in the previously measured parameters; these increases were reduced by the tested antioxidants, whereas glutathione (GSH) and superoxide dismutase (SOD) levels were decreased. Treatment with the antioxidants in question modulated these levels. Liposomal CUR has more hepatoprotective efficiency than CUR, and its efficacy was similar to that of DES. The histopathological examinations confirmed these results.Conclusions:Liposomal CUR may be useful for the prevention of CuSO4-induced liver injury. Cyclooxygenase 2 protein expression and DNA fragmentation were involved in CuSO4 toxicity and treatment.

Assessing the toxicity of copper oxide nanoparticles and copper sulfate in a tropical Chlorella

Copper (Cu) in the form of copper sulfate (CuSO4) and copper oxide nanoparticles (CuO NP), arising mainly from agro-industrial activities, is known to have an adverse impact on algae. This study aimed to compare the toxicity of CuSO4 and CuO NP in Chlorella sp., which was isolated from a farmland in Cameron Highlands, Malaysia. Toxicity testing (96 h) based on chlorophyll-a concentration was conducted on cultures grown in Bold’s Basal Medium (BBM) added with CuSO4 ranging from 0 (control) to 200 μM or CuO NP ranging from 0 to 2 mM. In addition, the effects of CuSO4 and CuO NP at EC10 and EC50 on the pigmentation, oxidative stress response, and cell morphology of Chlorella sp. were assessed. Results showed that Chlorella sp. was more sensitive to CuSO4 (EC50 = 150 μM) than CuO NP (EC50 = 1.30 mM). Exposure to CuSO4 at EC50 but not CuO NP reduced the chlorophyll-a, chlorophyll-b, and carotenoid contents of the algal cells. At 96 h, CuSO4 at EC50 induced significant increase in the production of reactive oxygen species (ROS) and degree of lipid peroxidation. Agglomerates of nanoparticles and algal cells were seen in cultures treated with CuO NP, whereas clumping of cells occurred in cultures exposed to CuSO4. Some CuO NP were found to penetrate the cell wall and be internalized into the algal cells. In conclusion, the toxicity of CuSO4 and CuO NP in Chlorella sp. differed in terms of their effects on growth, pigmentation, and oxidative stress response.

Effects of alginate oligomer on the expression of cell cycle- and stress-related genes in Chlamydomonas reinhardtii.

Enzymatically prepared alginate oligomer (AO) promoted the growth of Chlamydomonas reinhardtii in a concentration-dependent manner. AO at 2.5mg/mL induced increase in expression levels of cyclin A, cyclin B, and cyclin D in C. reinhardtii. CuSO4 at 100μM suppressed the growth of C. reinhardtiin, and AO at 2.5mg/mL significantly alleviated the toxicity of CuSO4. Increased intracellular reactive oxygen species level in C. reinhardtii induced by CuSO4 was reduced by AO. After cultivation with CuSO4 at 100μM, expression levels of ascorbate peroxidase and superoxide dismutase in C. reinhardtii were increased, and AO reduced the increased levels of these enzymes. These results suggest that AO exhibits beneficial effects on C. reinhardtii through influencing the expression of various genes not only at normal growth condition but also under CuSO4 stress.

Copper Nanoparticles and Copper Sulphate Induced Cytotoxicity in Hepatocyte Primary Cultures of Epinephelus coioides

Copper nanoparticles (Cu-NPs) were widely used in various industrial and commercial applications. The aim of this study was to analyze the cytotoxicity of Cu-NPs on primary hepatocytes of E.coioides compared with copper sulphate (CuSO4). Cultured cells were exposed to 0 or 2.4 mg Cu L-1 as CuSO4or Cu-NPs for 24-h. Results showed either form of Cu caused a dramatic loss in cell viability, more so in the CuSO4 than Cu-NPs treatment. Compared to control, either CuSO4 or Cu-NPs significantly increased reactive oxygen species(ROS) and malondialdehyde(MDA) concentration in hepatocytes by overwhelming total superoxide dismutase (T-SOD) activity, catalase(CAT) activity and glutathione(GSH) concentration. In addition, the antioxidative-related genes [SOD (Cu/Zn), SOD (Mn), CAT, GPx4] were also down-regulated. The apoptosis and necrosis percentage was significantly higher after the CuSO4 or Cu-NPs treatment than the control. The apoptosis was induced by the increased cytochrome c concentration in the cytosol and elevated caspase-3, caspase-8 and caspase-9 activities. Additionally, the apoptosis-related genes (p53, p38β and TNF-α) and protein (p53 protein) were up-regulated after the CuSO4 or Cu-NPs treatment, with CuSO4 exposure having a greater effect than Cu-NPs. In conclusion, Cu-NPs had similar types of toxic effects as CuSO4 on primary hepatocytes of E.coioides, but toxicity of CuSO4 was more severe than that of Cu-NPs.

Effect of β-glucan on behavioral, biochemical and hematological parameters against toxicity of copper sulfate in common carp Cyprinus carpio L.

The aim of the present study was to assess the effect of a commercial ß-glucan against acute toxic effect of copper sulfate on common carp Cyprinus carpio L. behavioral, hematological parameters and biochemical tests. A total of 250 Fish (150 ± 2 g) were fed a basal control diet or the basal diet plus a ß-glucan (1 g kg-1 diet) for 60 days. LC50 was calculated for 72 h which was 10.83 mg L-1. At the end of the trial, CuSO4.5H2O was added to all treatments at a dose of 5 mgL-1 for T1 and T2, 7mg L-1 for T3 and T4, 9 mgL-1 for T5 and T6 for 96h. Fish behavioral changes were recorded during 96h of exposure to different Cu concentrations with and without β-glucan, which showed abnormalities such as increase swimming activity, jerky movement, loss of equilibrium, respiratory stress, increase operculum movement, frequent jumping, erratic swimming and swimming near the water surface. On the other hand, ß-glucan supplemented groups showed significant increase (P≤0.05) in Hb concentration, PCV%, RBC and WBC count in comparison with groups without ß-glucan. The results of dietary groups without ß-glucan showed a significant decrease (P≤ 0.05) in Hb concentration, hematocrit value, RBC count, but there were significant increase (P≤ 0.05) in WBC count with an increase of Cu concentration compared to control groups.
 Results showed significant increase (P≤ 0.05) in dietary groups without ß-glucan in values of ALT, AST and ALP enzymes activity with elevation of Cu levels compared to control group. But, ß-glucan supplemented groups showed significant decrease (P ≤ 0.05) in values of ALT, AST and ALP enzymes activity in comparison with dietary groups without ß-glucan. These results suggested that β-glucan has protective effect against CuSO4 toxicity and future studies should be pursued particularly immune response and molecular studies

Effects of copper overload in P19 neurons: impairment of glutathione redox homeostasis and crosstalk between caspase and calpain protease systems in ROS-induced apoptosis.

Copper, a transition metal with essential biological functions, exerts neurotoxic effects when present in excess. The aim of the present study was to better elucidate cellular and molecular mechanisms of CuSO4 toxicity in differentiated P19 neurons. Exposure to 0.5mM CuSO4 for 24h provoked moderate decrease in viability, accompanied with barely increased generation of reactive oxygen species (ROS) and caspase-3/7 activity. Glutathione (GSH) and ATP contents were depleted, lactate dehydrogenase inactivated, and glyceraldehyde-3-phosphate dehydrogenase overexpressed. In severely damaged neurons exposed to only two times higher concentration, classical caspase-dependent apoptosis was triggered as evidenced by marked caspase-3/7 activation and chromatin condensation. Multifold increase in ROS, together with very pronounced ATP and GSH loss, strongly suggests impairment of redox homeostasis. At higher copper concentration protease calpains were also activated, and neuronal injury was prevented in the presence of calpain inhibitor leupeptin through the mechanism that affects caspase activation. MK-801 and nifedipine, inhibitors of calcium entry, and H-89 and UO126, inhibitors of PKA and ERK signaling respectively, exacerbated neuronal death only in severely damaged neurons, while ROS-scavenger quercetin and calcium chelator BAPTA attenuated toxicity only at lower concentration. In a dose-dependent manner copper also provoked transcriptional changes of genes involved in intracellular signaling and induction of apoptosis (p53, c-fos, Bcl-2 and Bax). The obtained results emphasize differences in triggered neuronal-death processes in a very narrow range of concentrations and give further insight into the molecular mechanisms of copper toxicity with the potential to improve current therapeutic approaches in curing copper-related neurodegenerative diseases.

Effects of Salinity Variations on Acute Toxicity of Copper Sulphate against Oreochromis niloticus Fingerlings in Laboratory Bioassays

The study was carried out to investigate the salinity tolerance and relative acute toxicity of copper sulphate (CuSO4) under fresh water in varying salinity level, against Oreochromis niloticus fingerlings. A total of 280 fingerlings of O. niloticus (mean weight; 20 ± 4 g; 4-6 weeks old) were used as test animals in this study. The test compound used was copper as CuSO4.5H2O analar grade (molecular weight 249.68 g). The dose response data were analyzed by probit analysis. The results showed that on the basis of daily mortality assessment, O. niloticus were unable to survive in water with salinity above 22ppt within a 24hr period, but the fish survived well at lower salinities below 12ppt. Based on 96hr LC50 values, toxicity of CuSO4 against the fingerlings increased with increase or decrease in salinity except at 12ppt where the toxicity was minimal. The significance of this study is in setting ecologically sound, safe limits that are relevant for the prevailing two hydrological seasons in the tropics for the discharge of heavy metals into lagoons and the advantages of breeding O. niloticus under typical brackish water conditions, instead of freshwater. Keywords: Acute toxicity, Fingerlings, Copper sulphate, Oreochromis niloticus, Salinity

The Effect of Composition of Different Ecotoxicological Test Media on Free and Bioavailable Copper from CuSO4 and CuO Nanoparticles: Comparative Evidence from a Cu-Selective Electrode and a Cu-Biosensor

The analysis of (bio)available copper in complex environmental settings, including biological test media, is a challenging task. In this study, we demonstrated the potential of a recombinant Pseudomonas fluorescens-based biosensor for bioavailability analysis of CuSO4 and CuO nanoparticles (nano-CuO) in seventeen different ecotoxicological and microbiologial test media. In parallel, free Cu in these test media was analysed using Cu-ion selective electrode (Cu-ISE). In the case of CuSO4, both free and bioavailable Cu decreased greatly with increasing concentration of organics and phosphates in the tested media. A good correlation between free and bioavailable Cu was observed (r = 0.854, p < 0.01) indicating that the free Cu content in biological test media may be a reasonably good predictor for the toxicity of CuSO4. As a proof, it was demonstrated that when eleven EC50 values for CuSO4 from different organisms in different test media were normalized for the free Cu in these media, the difference in these EC50 values was decreased from 4 to 1.8 orders of magnitude. Thus, toxicity of CuSO4 to these organisms was attributed to the properties of the test media rather than to inherent differences in sensitivity between the test organisms. Differently from CuSO4, the amount of free and bioavailable Cu in nano-CuO spiked media was not significantly correlated with the concentration of organics in the test media. Thus, the speciation of nano-CuO in toxicological test systems was not only determined by the complexation of Cu ions but also by differential dissolution of nano-CuO in different test conditions leading to a new speciation equilibrium. In addition, a substantial fraction of nano-CuO that was not detectable by Cu-ISE (i.e., not present as free Cu-ions) was bioavailable to Cu-biosensor bacteria. Thus, in environmental hazard analysis of (nano) particulate materials, biosensor analysis may be more informative than other analytical techniques. Our results demonstrate that bacterial Cu-biosensors either in combination with other analytical/speciation techniques or on their own, may serve as a rapid (eco)toxicological screening method.

Effects of copper on survival of prion protein knockout neurons and glia.

The N-terminal region of the prion protein (PrP) contains an octameric repeat region suggested to bind copper. A 32-amino acid peptide (PrPOcta) based on this region in the protein was tested for its effects on cultured cerebellar cells. Cerebellar cells from mice deficient in cellular PrP (Prnp0/0 mice) are more sensitive to copper toxicity and oxidative stress. PrPOcta selectively promotes the survival of Prnp0/0 cerebellar cells. However, PrPOcta also reduces the toxicity of CuSO4 on cerebellar cells and abolishes the difference in increased sensitivity of Prnp0/0 cells to both copper toxicity and also oxidative stress from xanthine oxidase. PrPOcta does not promote the survival or proliferation of astrocytes or microglia. The survival-promoting effects of PrPOcta on neurons may be due to its ability to effectively chelate copper. The octameric repeat region of PrP may represent a functional domain of the native protein.

Studies on Peroxidation in Rats Ingesting Copper Sulphate and Effect of Subsequent Treatment with Ocimum sanctum.

This study was aimed at determining the basic biochemical changes induced by the toxicity of copper sulphate (CuSO4) and analyzing the detoxifying effects of Ocimum sanctum, a medicinal plant commonly used in India. CuSO4 dissolved in saline was injected into rats for 30 days. Determinations of serum or tissue level of copper, lipid peroxides, iron, ferritin and antiperoxidative enzymes like SOD, CAT, GSH, GST, GPx, and ceruloplasmin were then carried out. CuSO4 toxicity manifested itself as significantly increased production of lipid peroxides from lipid products by a free-radical mechanism involving hydroxyl free radicals. The anti-oxidant enzyme levels were also notably increased in CuSO4 toxicity, but not to the extent of substantially reducing the hydroxyl free radicals produced by CuSO4. Ocimum sanctum administration restored the various parameters to near their normal values.

Diffusion assays for determination of the effects of pH on the toxicity of heavy metal compounds towards filamentous fungi

Abstract Well diffusion assays and two‐dimensional gradient plates were of use in determining the effects of external pH on the toxicity of CuSO4, HgCl2 and phenyl mercuric acetate towards a range of filamentous fungi. Such techniques also enabled assessment of the relative toxicities of the different compounds and differentiation of tolerant and sensitive species. For most of the organisms, a decrease in toxicity was evident with increasing pH.

Differential uptake and toxicity of ionic and chelated copper in Triticum aestivum

Plants of Triticum aestivum L. cv. Atlas-66 were grown in nutrient solutions containing 0–50 μM Cu as CuSO4 or 0–800 μM Cu as Cu-EDTA to compare the toxic effects of ionic and chelated Cu when yield reductions were similar in magnitude. Plants exposed to 50 μM CuSO4 accumulated 43 ± 6 μg g−1 Cu in leaf tissues and 2300 ± 130 μg g−1 in root tissues. Plants injured by CuSO4 showed acute signs of Cu toxicity; leaves showed mild necrosis and symptoms of induced Fe deficiency and root growth and lateral root initiation were inhibited. Concentrations of Fe, Mn, and Mg in leaves of plants injured by CuSO4 were low, possibly leading to nutrient deficiencies. Concentrations of Ca in leaves were also low, but were above levels considered to be deficient. Plants exposed to 800 μM Cu-EDTA accumulated 260 ± 7 μg g−1 Cu in leaf tissues and 6600 ± 1200 μg g−1 Cu in root tissues. Despite higher tissue concentrations of Cu, plants injured by Cu-EDTA showed systemic toxicity symptoms, possibly reflecting induced Fe deficiency as the primary toxic effect. Leaves of plants injured by Cu-EDTA showed mild necrosis and symptoms of induced Fe deficiency, root growth was depressed (but to a lesser extent than with CuSO4), and lateral root initiation was unaffected. Concentrations of Fe in leaves of plants injured by Cu-EDTA were lower than plants grown with micronutrient levels of Cu, while concentrations of Mn, Ca, and Mg in leaves of Cu-EDTA injured plants were higher. Differential toxicity of CuSO4 and Cu-EDTA could occur if Cu-EDTA were absorbed across the plasma membrane as an intact complex or if the primary toxic effect of CuSO4 and Cu-EDTA were on membrane structure and (or) function.