Preventive Effects of Zinc Against Psychological Stress-Induced Iron Dyshomeostasis, Erythropoiesis Inhibition, and Oxidative Stress Status in Rats

Psychological stress (PS) could cause decreased iron absorption and iron redistribution in body resulting in low iron concentration in the bone marrow and inhibition of erythropoiesis. In the present study, we investigated the effect of zinc supplementation on the iron metabolism, erythropoiesis, and oxidative stress status in PS-induced rats. Thirty-two rats were divided into two groups randomly: control group and zinc supplementation group. Each group was subdivided into two subgroups: control group and PS group. Rats received zinc supplementation before PS exposure established by a communication box. We investigated the serum corticosterone (CORT) level; iron apparent absorption; iron contents in liver, spleen, cortex, hippocampus, striatum, and serum; hematological parameters; malondialdehyde (MDA); reduced glutathione (GSH); and superoxide dismutase (SOD). Compared to PS-treated rats with normal diet, the PS-treated rats with zinc supplementation showed increased iron apparent absorption, serum iron, hemoglobin, red blood cell, GSH, and SOD activities; while the serum CORT; iron contents in liver, spleen, and regional brain; and MDA decreased. These results indicated that dietary zinc supplementation had preventive effects against PS-induced iron dyshomeostasis, erythropoiesis inhibition, and oxidative stress status in rats.     

Evaluation of Long-Term Toxicity of Oral Zinc Oxide Nanoparticles and Zinc Sulfate in Mice

The toxicological effects of zinc oxide nanoparticles (nano-ZnOs) are related to their dissolution and interference with zinc ion homeostasis. High-soluble zinc sources may produce more severe and acute toxicity; however, the evaluation of potential toxicity of long-term exposure to nano-ZnOs and high-soluble sources of zinc remains obscure. This study aimed at evaluating effects of nano-ZnOs and zinc sulfate on development, serum and hematological parameters, and mineral concentrations in selected tissues and intestinal microbiota in mice via gastrointestinal administration for 7 weeks. Results indicated that 250 mg/kg nano-ZnOs reduced the body weight from weeks 8 to 11, increased serum glutamic-pyruvic transaminase activity, and increased the zinc concentrations of the serum, liver, and kidney while did not affect the relative organ weight, intestinal microbiota, and other mineral concentrations (Fe, Cu, and Mn) in the kidney, liver, and thigh muscle. Oral administration with 250 mg/kg zinc sulfate seemed to show more severe and acute toxicity since mice in zinc sulfate group exhibited reduced body weight from weeks 5 to 11, decreased relative pancreas weight, and increased serum glutamic-oxalacetic transaminase activity and intestinal enteric group.     

A Combination of a Dairy Product Fermented by Lactobacilli and Galactooligosaccharides Shows Additive Effects on Mineral Balances in Growing Rats with Hypochlorhydria Induced by a Proton Pump Inhibitor

This study aimed to investigate the effects of a combination of a dairy product fermented by lactobacilli (DFL) and galactooligosaccharides (GOS) on mineral balances in growing rats with hypochlorhydria induced by a proton pump inhibitor (PPI). Three-week-old male rats were assigned to receive one of six diets: a control diet, control diets containing 1.6 or 5.0 % GOS, a DFL diet and DFL diets containing 1.6 or 5.0 % GOS for 9 days. From day 5 of the feeding period, half of the rats fed with control diets were subcutaneously administered with saline, whereas the remaining rats were administered with PPI for 5 days. Calcium (Ca), phosphorus (P), magnesium (Mg), iron (Fe) and zinc (Zn) balances were determined from days 6 to 9. PPI administration significantly decreased the apparent absorption of Ca and Fe and increased urinary P excretion, resulting in decreased Ca, Fe and P retention. GOS dose-dependently increased the apparent absorption of Ca, Mg and Fe and urinary Mg excretion and decreased urinary P excretion. DFL significantly increased the apparent absorption of Ca and Mg and urinary Mg excretion. The combination of DFL and GOS additively affected these parameters, resulting in increased Ca, P and Fe retention, and it further increased the apparent absorption and retention of Zn at 5.0 % GOS. In conclusion, the combination of DFL and GOS improves Ca, P and Fe retention in an additive manner and increases the Zn retention in growing rats with hypochlorhydria induced by PPI.     

Resveratrol Attenuates Copper and Zinc Homeostasis and Ameliorates Oxidative Stress in Type 2 Diabetic Rats

Diabetes is a common metabolic disorder characterized by elevated blood glucose level. Trace element homeostasis causes disturbances in diabetes due to hyperglycemia. Superoxide dismutase (SOD), an antioxidant enzyme, contains zinc and copper ions as its cofactors. Defects in SOD level and activity have been observed in diabetes. Resveratrol (RSV) has displayed hypoglycemic effects and is proven to improve oxidative stress. The aim of the present study was to examine the possible effects of RSV on blood glucose level, serum copper and zinc levels, SOD, and a number of other oxidative markers in type 2 diabetic rats. Diabetes was induced in male Wistar rats with administration of streptozotocin and nicotine amide. The studied groups containing six animals per group were as follows: group 1 normal control group; group 2 diabetic control group; groups 3, 4, and 5 diabetic rats that received 1, 5, and 10 mg/kg body weight of RSV, respectively for 30 days. Serum glucose, copper, zinc, SOD activity, total oxidant status (TOS) as well as thiol groups were all measured. Blood glucose in RSV treated groups significantly decreased. Similarly, copper significantly decreased in diabetic groups treated with RSV. Treatment with 10 mg/kg RSV resulted in significantly increased serum zinc. Furthermore, Cu/Zn ratio was observed to decrease in treated groups compared with untreated diabetic control group. RSV treated groups revealed an increased level of SOD activity as well as improved oxidative status. In summary, the results showed that RSV has potential hypoglycemic effect, attenuates trace element homeostasis, and consequently increases SOD activity level.     

Effect of Zinc Supplementation on Inflammatory Markers and Adipokines in Young Obese Women

Obesity is a chronic inflammatory state characterized by altered adipokine production and increased levels of inflammatory cytokines. The study explored the effect of zinc supplementation on inflammatory markers and adipocyte hormones in young obese women. Twenty five non-obese women and forty obese women (body mass index ≥25 kg/m²) aged 19–28 years were recruited for this study. Twenty obese women of the study group took 30 mg/day of supplemental zinc as zinc gluconate for 8 weeks and 20 obese women of control group took placebo. Usual dietary zinc intake was estimated from 3-day diet records. Serum zinc and urinary zinc concentration were measured by Atomic Absorption Spectrophotometry. Inflammatory markers such as high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-6 and adipocyte hormones such as lepin and adiponectin were measured by enzyme immunoassay. Inflammatory markers and leptin were significantly higher, but adiponectin was significantly lower in obese women than non-obese women. Zinc supplementation increased serum zinc by 15 % and urinary zinc by 56 % (P?<?0.05). The levels of hs-CRP (P?=?0.03) and IL-6 (P?=?0.006) significantly decreased with zinc supplementation, but not in placebo group. Serum leptin and plasma adiponectin concentration did not differ with either zinc supplementation or placebo. The levels of IL-6 and leptin were inversely associated with dietary zinc intake. These results suggest that zinc may have a favorable effect on obesity-related inflammation in young adults.     

Changes in Serum Copper and Zinc Levels in Peripartum Healthy and Subclinically Hypocalcemic Dairy Cows

The objective of this study was to determine the levels of serum copper and zinc in subclinically hypocalcemic peripartum dairy cows in comparison to healthy animals. Blood samples were taken from 219 multiparous Holstein cows near parturition (from 4 weeks prepartum to 4 weeks postpartum) and 51 cows with subclinical hypocalcemia. The results showed that the serum copper concentration increased gradually at 1 week prepartum and remained high for the first 4 weeks postpartum in the healthy periparturient dairy cows. The serum zinc concentration reached a nadir at 1 week postpartum and subsequently increased gradually to baseline. The serum zinc concentration was significantly decreased (P?<?0.01) in dairy cows with subclinical hypocalcemia compared with healthy cows. There was no significant difference in the serum copper concentration between cows with subclinical hypocalcemia and healthy cows. These data demonstrate that the concentrations of copper and zinc in serum change dramatically during the peripartum period in dairy cows, which is a tremendous challenge for the body and for the maintenance of dairy cow health. The present study further suggests that a decreased serum zinc concentration could be a cause of decreased productive performance and increased susceptibility to other diseases due to immunosuppression in dairy cows with subclinical hypocalcemia. Additionally, this decreased zinc concentration may be involved in the pathogenesis of subclinical hypocalcemia.     

Dietary Zinc Deficiency Effects Dorso-lateral and Ventral Prostate of Wistar Rats: Histological,Biochemical and Trace Element Study

Zinc deficiency has become a global problem affecting the developed and developing countries due to inhibitors in the diet which prevents its absorption or due to a very low concentration of bioavailable zinc in the diet. Being present in high concentration in the prostate and having diverse biological function, we investigated the effects of dietary zinc deficiency for 2 and 4 weeks on dorso-lateral and ventral prostate. Sixty prepubertal rats were divided into three groups: zinc control (ZC), pair fed (PF) and zinc deficient (ZD) and fed on 100 μg/g (zinc control and pair fed groups) and 1 μg/g (zinc deficient) diet. Zinc deficiency was associated with degenerative changes in dorso-lateral and ventral prostate as made evident by karyolysis, karyorhexis, cytoplasmolysis, loss of cellularisation, decreased intraluminar secretion and degeneration of fibromuscular stroma. In response, protein carbonyl, nitric oxide, acid phosphatase, 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase increased, exhibiting variable level of significance. Total protein and total zinc concentration in dorso-lateral and ventral prostate as well as in serum decreased (P?P?相似文献   

Dietary and Non-dietary Factors Associated with Serum Zinc in Indian Women

Women in low-income settings, common in India, are at risk of inadequate zinc intake due to poor diet quality and low consumption of flesh foods rich in zinc. The aims of this study were to assess the prevalence of zinc status of non-pregnant rural and tribal women living in central India and to identify dietary and non-dietary factors associated with the biochemical zinc status of these women. Rural and tribal non-pregnant women 18–30 years of age were selected using proportion to population sampling near Nagpur, Maharashtra, India. Sociodemographic, biochemical (serum zinc), clinical, and dietary data (1-day interactive 24-h recall) were collected. The mean age of women (n?=?109; rural?=?52; tribal?=?56) was 23.2 years and mean BMI was 17.9 kg/m². The majority of the participants identified as being non-vegetarian (72 %). The mean?±?SD serum zinc concentration was 10.8?±?1.6 μmol/L, and 52 % of participants had a low serum zinc concentration according to the International Zinc Nutrition Consultative Group (IZiNCG). The median (first and third quartile) energy, zinc intake, and phytate/zinc molar ratio was 5.4 (4.2, 6.7)?MJ/day, 5.3 (3.8, 7.0)?mg/day, and 26 (22, 28), respectively. Zinc intakes were well below IZiNCG recommendations for dietary zinc of 9 mg/day for non-pregnant women aged 14–18 years and 7 mg/day for non-pregnant women aged ≥19 years. Using linear regression analysis to identify non-dietary and dietary factors associated with serum zinc, a significant association was only found for current lactation (p?=?0.012) and energy intake (p?相似文献   

The Influence of Supplementation of Different Forms of Zinc in Goats on the Zinc Concentration in Blood Plasma and Milk

The aim of the experiment was to study zinc concentration in goat’s milk during a short-term oral supplementation of three organic and one inorganic form of zinc and the influence of Zn supplementation on the concentration of Zn and Cu in blood plasma. The experiment involved 31 lactating goats. The group C was the control, group L received zinc lactate, group A received zinc chelate, group T received amino acid–polypeptidic complex with zinc, and group O received zinc oxide. Zinc preparations were administered orally in 500 mg Zn per animal for 28 days. In the course of the experiment, Zn concentration in plasma increased significantly in all experimental groups and in the control group was unchanged. The concentration of zinc in milk during the experiment fluctuated in individual groups, but there were no significant differences between groups. After 28 days of Zn supplementation, Zn concentration in milk of goats was similar as at the start of the experiment in all groups. According to our results, the supplementation of different forms of zinc did not influence the concentration of Zn in milk, but significantly influenced the Zn concentration in blood plasma. The efficiency of different organic and inorganic forms of zinc was similar.     

Selenium Supplementation Modulates Zinc Levels and Antioxidant Values in Blood and Tissues of Diabetic Rats Fed Zinc-Deficient Diet

Diabetes mellitus is associated to a reduction of antioxidant defenses that leads to oxidative stress and complications in diabetic individuals. The present study was undertaken to investigate the effect of selenium on blood biochemical parameters, antioxidant enzyme activities, and tissue zinc levels in alloxan-induced diabetic rats fed a zinc-deficient diet. The rats were divided into two groups; the first group was fed a zinc-sufficient diet, while the second group was fed a zinc-deficient diet. Half of each group was treated orally with 0.5 mg/kg sodium selenite. Tissue and blood samples were taken from all animals after 28 days of treatment. At the end of the experiment, the body weight gain and food intake of the zinc-deficient diabetic animals were lower than that of zinc-adequate diabetic animals. Inadequate dietary zinc intake increased glucose, lipids, triglycerides, urea, and liver lipid peroxidation levels. In contrast, serum protein, reduced glutathione, plasma zinc and tissue levels were decreased. A zinc-deficient diet led also to an increase in serum glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, and liver glutathione-S-transferase and to a decrease in serum alkaline phosphatase activity and glutathione peroxidase. Selenium treatment ameliorated all the values approximately to their normal levels. In conclusion, selenium supplementation presumably acting as an antioxidant led to an improvement of insulin activity, significantly reducing the severity of zinc deficiency in diabetes.     

Effects of vitamin C on the hypobaric hypoxia-induced immune changes in male rats

Hypobaric hypoxia (HH) induces oxidative stress (OS) and is associated with the generation of reactive oxygen species (ROS). Vitamin C is an efficient antioxidant, and it is used in a high-altitude environment to reduce the OS. The present study explores the role of vitamin C on some HH-induced changes of immune parameters in rats which were exposed to HHc condition at 18,000 ft in a simulated chamber for 8 h/day for 6 days with and without vitamin C administration at three different doses (200, 400, and 600 mg/kg body wt). The phagocytic activity of circulating blood WBC was increased, and the cytotoxic activity of splenic mononuclear cell (MNC) and the delayed type of hypersensitivity (DTH) responses to bovine serum albumin (BSA) were decreased in rats exposed to HHc condition, but these immune changes were blocked after administration of vitamin C at 400 mg/kg body wt. The leukocyte adhesive inhibition index (LAI) was not altered either in HHc condition or after administration of vitamin C in HHc condition. The serum corticosterone (CORT) concentration was increased in rats exposed to HHc condition which was blocked after administration of vitamin C (400 mg/kg body wt). The immune parameters and serum CORT concentration, however, did not show any recovery after administration of vitamin C at the dose of 200 and 600 mg/kg body wt. The present study indicates that administration of vitamin C at a dose of 400 mg/kg body wt may prevent the HH-induced immunological changes but not at the lower dose (200 mg/kg body wt) or higher dose (600 mg/kg body wt) in rats.     

Tracing of Zinc Nanocrystals in the Anterior Pituitary of Zinc-Deficient Wistar Rats

The aim of this study was to trace zinc nanocrystals in the anterior pituitary of zinc-deficient Wistar rats by using autometallographic technique. Male Wistar rats (30–40 days of age, pre-pubertal period) of 40–50 g body weight were divided into the following: the ZC (zinc control) group—fed with 100 ppm zinc in diet, the ZD (zinc-deficient) group—fed with zinc-deficient (1.00 ppm) diet and the PF (pair-fed) group—received 100 ppm zinc in diet. The experiments were set for 2 and 4 weeks. Pituitary was removed and processed for the autometallographic technique. The control and pair-fed groups retained their normal morphological features. However, male Wistar rats fed on zinc-deficient diet for 2 and 4 weeks displayed a wide range of symptoms such as significant (P < 0.05) decrease in diet consumption, body weight and pituitary weight and decrease in gradation of intensity of zinc nanocrystals in the nuclei. The present findings suggest that the dietary zinc deficiency causes decreased intensity of zinc nanocrystals localization and their distribution in the pituitary thereby contributing to the dysfunction of the pituitary of the male Wistar rats. The severity of zinc deficiency symptoms progressed after the second week of the experiment. Decreased intensity of zinc nanocrystals attenuates the pituitary function which would exert its affect on other endocrine organs impairing their functions indicating that the metabolic regulation of pituitary is mediated to a certain extent by zinc and/or hypothalamus-hypophysial system which also reflects its essentiality during the period of growth.     

Effects of Dietary Zinc Oxide Nanoparticles on Growth Performance and Antioxidative Status in Broilers

Broilers in four groups were fed a basal diet supplemented with 60 mg/kg zinc oxide (60-ZnO; control), or 20, 60, or 100 mg/kg ZnO nanoparticles (20-, 60-, and 100-nano-ZnO, respectively). Compared with the controls, after 14 days, birds in the 20- and 60-nano-ZnO groups had significantly greater weight gains and better feed conversion ratios. However, the body weight of birds in the 100-nano-ZnO group was dramatically reduced after 28 days. Relative to the control group, the total antioxidant capability (T-AOC) in serum and liver tissue was significantly higher in the 20-nano-ZnO group at all time points and also significantly higher in the 60- and 100-nano-ZnO groups in serum on days 28 and 35 and in liver tissues on days 21 and 28. Compared with the controls, the activity of copper-zinc superoxide dismutase (Cu-Zn-SOD) was significantly greater in the 60- and 100-nano-ZnO groups in serum on days 28 and 35 and in liver tissues after 21 days. Catalase activity in serum samples was significantly higher in the 20- and 60-nano-ZnO groups relative to the control and 100-nano-ZnO birds, but catalase activity in liver tissue was not affected by different nano-ZnO levels. Malondialdehyde content in serum and liver tissues was significantly reduced in the 20-, 60-, and 100-nano-ZnO groups compared with that in the control group at all time points except day 42. Taken together, our data indicate that appropriate concentration of dietary ZnO nanoparticles improves growth performance and antioxidative capabilities in broilers, and 20 mg/kg nano-ZnO is the optimal concentration.     

Antidiabetic and Pancreas-Protective Effects of Zinc Threoninate Chelate in Diabetic Rats may be Associated with its Antioxidative Stress Ability

Zinc exerts a wide range of important biological roles. The present study was carried out to investigate the effects of zinc threoninate chelate in blood glucose levels, lipid peroxidation, activities of antioxidant defense systems and nitrite concentration, and histology of the pancreas in diabetic rats. Wistar rats were intravenously injected with a single dose of streptozotocin to induce diabetes. Then, diabetic rats were administrated orally with zinc threoninate chelate (3, 6, and 9 mg/kg body weight) once daily for 7 weeks. Fasting blood glucose was monitored weekly. At the end of the experimental period, the diabetic rats were killed, and levels of serum insulin, malondialdehyde, and nitric oxide, activities of glutathione peroxidase, total superoxide dismutase, copper/zinc-superoxide dismutase, and nitric oxide synthase were determined; pancreas was examined histopathologically as well. Zinc threoninate chelate significantly reduced the blood glucose levels and significantly increased the serum insulin levels in diabetic rats. In addition, zinc threoninate chelate caused a significant increase in activities of antioxidant enzymes and significant decrease in nitrite concentration and malondialdehyde formation in the pancreas and serum of diabetic rats. These biochemical observations were supplemented by histopathological examination of the pancreas. These results suggested that the antidiabetic effect of zinc threoninate chelate may be related to its antioxidative stress ability in diabetic rats.     

缺锌对大鼠血液皮质醇和ACTH含量及大脑皮质NO合酶活性的影响

就缺锌对大鼠血液皮质醇和促肾上腺皮质激素（ACTH）含量以及大脑皮质NO合酶活性的影响进行了研究,生长大鼠随机分为3组,即缺锌组,对喂组和缺锌补锌组（先饲喂缺锌饲料21天后再补锌）,饲养实验的持续时间为35d。与对喂组比较,缺锌组大鼠血液中皮质醇含量显著升高,而血液ACTH浓度以及大脑皮质NO合酶活性明显降低,此结果提示锌可影响下丘脑－垂体一肾上腺皮质轴和NO合酶的代谢。     

Effects of Subchronic Aluminum Exposure on Serum Concentrations of Iron and Iron-Associated Proteins in Rats

The purpose of the study was to investigate the effect of subchronic aluminum (Al) exposure on iron (Fe) homeostasis in rats. One hundred Wistar rats were divided into two groups. Experimental rats were given drinking water containing aluminum chloride (AlCl₃, 430 mg Al³⁺·L^?1), while control rats were given distilled water for up to 150 days. Ten rats were sacrificed in each group every 30 days. Mean corpuscular hemoglobin (MCH), and serum levels of Al, Fe, transferrin (TF), total iron binding capacity (TIBC), and soluble transferrin receptor (sTfR) were measured. Al-treated rats showed significantly decreased bodyweight and increased Al and Al/Fe levels during the experimental period. Fe levels and MCH were higher on day 150 in the experimental group than in the control group. TF content and TIBC were higher, whereas erythrocyte counts and sTfR content were lower in the experimental group than in the control group from days 90 and 60, respectively. Longer duration of Al administration increased the serum levels of Al, TF, Al/Fe, and TIBC and decreased sTfR. MCH and Fe levels decreased first, and then increased. The results indicate that chronic exposure to Al disturbed Fe homeostasis.     

Evidence of Zinc in Affording Protection Against X-Ray-Induced Brain Injury in Rats

In the present world, X-rays have been regarded as one of the most efficient tools in medicine, industry and research. On the contrary, extensive human exposure to these rays is responsible for causing detrimental effects on physiological system. The aim of the present study was to investigate the role of zinc (Zn), if any, in mitigating the adverse effects induced by fractionated X-irradiation on rat brain. Female Sprague-Dawley rats weighing 170–200 g were divided into four different groups viz.: (a) normal control, (b) X-irradiated (21Gy), (c) zinc treated (227 mg/L in drinking water) and (d) X-irradiated + zinc treated. The skulls of animals belonging to groups (b) and (d) were exposed to X-rays in 30 fractions. Each fraction delivered a radiation dose of 70 rads, and rats were exposed to two fractions every day for 15 days, consecutively. X-ray treatment resulted in significant alterations in the neurobehavior, neurotransmitter levels and neuro-histoarchitecture of rats, whereas zinc co-treatment with X-rays resulted in significant improvement in these parameters. X-ray exposure also caused a significant increase in the levels of lipid peroxidation as well as activities of catalase and superoxide dismutase, which however were decreased upon simultaneous Zn treatment. On the contrary, X-ray treatment down-regulated the glutathione system, which were found to be up-regulated by zinc co-treatment. Further, protein expressions of p53 and NF-?B were found to be significantly elevated after X-irradiation, which were reversed following Zn supplementation. Hence, Zn seems to be an effective agent in mitigating the detrimental effects caused by exposure to X-rays.     

五味子对实验性水上漂浮及高强度运动大鼠垂体-性腺轴的影响

目的研究五味子对实验性水上漂浮及高强度运动大鼠垂体-性腺轴的影响。方法 34只SD大鼠随机分为非应激对照组（A组,n=10）、应激对照组（B组,n=12）和五味子干预组（C组,n=12）。A组不接受任何刺激,在生理盐水灌胃1周后进行取样。B组和C组进行为期10 d的递增负荷跑台训练,分别用生理盐水和五味子灌胃1周后,行3 h水上漂浮及3 h跑台高强度运动,结束即刻取血,测定血清皮质酮（CORT）、睾酮（T）、黄体生成素（LH）;随机取一侧睾丸,HE染色观察组织病理结构;电子显微镜下观察超微结构。结果 （1）B组大鼠与A组相比,睾酮水平显著下降;C组大鼠与B组相比,睾酮水平无明显变化,皮质酮水平显著降低;黄体生成素在3组之间均无显著变化。（2）HE染色示3组大鼠睾丸组织病理无明显变化。（3）电子显微镜观察发现,B组大鼠睾丸Leydig细胞线粒体肿胀,电子密度增高;C组大鼠睾丸Leydig细胞线粒体结构趋向于正常,可见分泌颗粒。结论五味子对实验性水上漂浮及高强度运动大鼠睾酮水平无明显作用,对睾丸超微结构有一定保护作用。     

Biochemical, Histological, and Memory Impairment Effects of Chronic Copper Toxicity: A Model for Non-Wilsonian Brain Copper Toxicosis in Wistar Rat

Animal models of copper toxicosis rarely exhibit neurological impairments and increased brain copper accumulation impeding the development of novel therapeutic approaches to treat neurodegenerative diseases having high brain Cu content. The aim of this study was to investigate the effects of intraperitoneally injected copper lactate (0.15 mg Cu/100 g body weight) daily for 90 days on copper and zinc levels in the liver and hippocampus, on biochemical parameters, and on neurobehavioral functions (by Morris water maze) of male Wistar rats. Copper-administered animals exhibited significantly decreased serum acetylcholinesterase (AChE) activity and impaired neuromuscular coordination and spatial memory compared to control rats. Copper-intoxicated rats showed significant increase in liver and hippocampus copper content (99.1 and 73 % increase, respectively), 40.7 % reduction in hepatic zinc content, and interestingly, 77.1 % increase in hippocampus zinc content with concomitant increase in copper and zinc levels in serum and urine compared to control rats. Massive grade 4 copper depositions and grade 1 copper-associated protein in hepatocytes of copper-intoxicated rats were substantiated by rhodanine and orcein stains, respectively. Copper-intoxicated rats demonstrated swelling and increase in the number of astrocytes and copper deposition in the choroid plexus, with degenerated neurons showing pyknotic nuclei and dense eosinophilic cytoplasm. In conclusion, the present study shows the first evidence in vivo that chronic copper toxicity causes impaired spatial memory and neuromuscular coordination, swelling of astrocytes, decreased serum AChE activity, copper deposition in the choroid plexus, neuronal degeneration, and augmented levels of copper and zinc in the hippocampus of male Wistar rats.