Effect of nickel chloride on streptozotocin-induced diabetes in rats

The potential of nickel chloride to prevent streptozotocin-induced hyperglycemia was tested in rats in vivo. To induce diabetes, streptozotocin (100 mg/kg body weight) was injected as a single dose. Streptozotocin treatment resulted in a significant decrease in plasma insulin and ceruloplasmin, and pancreatic Cu, protein, and Cu-Zn superoxide dismutase activity. In rats treated with nickel chloride (10 mg/kg body weight) and streptozotocin, these values were comparable with those observed in control rats. The results indicate that nickel chloride injected before streptozotocin prevented streptozotocin-induced hyperglycemia, and suggest that the protective effect was related to Cu-Zn superoxide dismutase activity, mediated by copper.     

Intratracheal injection of nickel chloride and copper-zinc superoxide dismutase activity in lung of rats.

Superoxide radical (O2-) is a free radical that may be involved in various toxic processes. Cu--Zn superoxide dismutase catalyses the dismutation of the superoxide free radical and protects cells from oxidative damage, and it has been used clinically. The concentration of Ni2+ and Cu--Zn superoxide dismutase activity were measured in lungs of rats at time intervals of 5, 12, 19, 26, 33, and 40 days following an intratracheal injection of 127 nmol of NiCl2. Nickel chloride increased nickel content and resulted in a significant increase of Cu--Zn superoxide dismutase activity in lungs. This elevation of Cu--Zn superoxide dismutase activity was highest on the 12th day (approximately threefold) and is at levels comparable to controls rats on day 40 onwards. Since Cu--Zn superoxide dismutase activity was increased in lung throughout our experimental period without corresponding increases of Cu2+ and Zn2+, we speculate that the elevation of Cu--Zn superoxide dismutase activity might be due to an increased half-life of the enzyme, induced by nickel.     

Acorus calamus extracts and nickel chloride

Nickel, a major environmental pollutant, is known for its clastogenic, toxic, and carcinogenic potential. In this article, we report the effect of Acorus calamus on nickel chloride (NiCl₂)-induced renal oxidative stress, toxicity, and cell proliferation response in male Wistar rats. NiCl₂ (250 μmol/kg body weight/mL) enhanced reduced renal glutathione content (GSH) glutathione-S-transferase (GST), glutathione reductase (GR), lipid peroxidation (LPO), H₂O₂ generation, blood urea nitrogen (BUN), and serum creatinine with a concomitant decrease in the activity of glutathione peroxidase (GPx) (p<0.001). NiCl₂ administration also dose-dependently induced the renal ornithine decarboxylase (ODC) activity several-fold as compared to salinetreated control rats. Similarly, renal DNA synthesis, which is measured in terms of [³H] thymidine incorporation in DNA, was elevated following NiCl₂ treatment. Prophylactic treatment of rats with A. calamus (100 and 200 mg/kg body weight po) daily for 1 wk resulted in the diminution of NiCl₂-mediated damage, as evident from the downregulation of glutathione content, GST, GR, LPO, H₂O₂ generation, BUN, serum creatinine, DNA synthesis (p<0.001), and ODC activity (p<0.01) with concomitant restoration of GPx activity. These results clearly demonstrate the role of oxidative stress and its relation to renal disfunctioning and suggest a protective effect of A. calamus on NiCl₂-induced nephrotoxicity in a rat experimental model.     

Dietary iron-deficiency up-regulates hephaestin mRNA level in small intestine of rats

Hephaestin is a protein, recently found from the study of sla (sex-linked anemia) mouse. Hephaestin is suggested to transport iron from intestinal enterocytes into the circulation. Iron is essential for living and for humans to maintain a constant total iron concentration in whole body. In this study, it was found that dietary iron-deficiency up-regulated hephaestin mRNA level in the proximal small intestine of rats. Therefore, it is suggested that in dietary iron-deficiency, hephaestin gene expression in proximal small intestine is up-regulated to absorb more iron from diet.     

Intestinal permeability to lactulose and mannitol in growing rats with iron-deficiency anemia

Iron deficiency can have nonhematological manifestations, some of which may affect the gastrointestinal tract. The aim of this study was to determine if iron-deficiency anemia in growing rats affected small-bowel permeability as assessed by the urinary ratio of lactulose and mannitol. Thirty-seven male Harlan Sprague-Dawley rats (21 d of age) were randomly divided into two groups and fed either an iron-deficient (n=19) or an iron-sufficient diet (n=18) that contained either 13.5 or 43.8 mg of iron/kg diet, respectively. Animals were evaluated between 25 and 38 d of dietary treatment. Intestinal permeability was assessed by measuring the lactulose/mannitol urinary ratio following administration of a solution that contained the two sugars. At the end of the study, the mean body weight of rats fed the low-iron diet was approx 95% that of the controls. The mean hemoglobin (g/dL) was significantly lower in the low-iron diet group (11.2±1.4) than in the control group (16.9±0.8) (p=0.001). The liver iron concentration (μg/g) of the anemic group (41.4±4.7) was also statistically (p=0.001) lower than in the control group (116.6±18.2). The lactulose/mannitol ratio was lower in the anemic rats (2.0±0.7) than in the control group (2.6±0.7) (p=0.008), a finding that is not suggestive of intestinal mucosal atrophy, previously described in anemic children.     

Effect of nitrous oxide on nickel deprivation in rats

Because nickel may have a biological function in a pathway in which vitamin B₁₂ is important, an experiment was performed to determine the effects of nitrous oxide exposure in rats deprived of nickel. Exposure to nitrous oxide (N₂O) causes inactivation of cobalamin and a subsequent decrease in the vitamin B₁₂-dependent enzymes methionine synthase and methylmalonyl CoA mutase. Rats were assigned to dietary groups of 12 in a factorially arranged experiment with dietary variables of nickel (0 or 1 μg/g) and vitamin B₁₂ (0 or 50 ng/g). After 6 wk, one-half of the rats from each dietary group were exposed to 50% N₂O/50% O₂ for 90 min/d for the last 28 d of the experiment. Vitamin B₁₂, N₂O, or their interaction had numerous effects; classical findings included N₂O-induced reduction in plasma vitamin B₁₂ and decreases in the vitamin B₁₂-dependent enzymes. Inactivation of vitamin B₁₂ by N₂O, however, did not exacerbate signs of nickel deprivation, possibly because the rats were able to metabolically compensate to N₂O exposure. Mention of a trademark or proprietary product in this article does not constitute a guarantee or warranty of the product by the United States Department of Agriculture and does not imply its approval to the exclusion of other products that may also be suitable.     

lipid peroxidation in liver of mice administrated with nickel chloride

The relationship between Ni-induced hepatic lipid peroxidation (LPO) and the concentrations of Ni and trace elements was investigated in male ICR mice. The protective effects of antioxidants were also examined. Hepatic LPO and the concentrations of Ni, Fe, Cu, and Zn in the liver were enhanced after an ip injection of nickel chloride (NiCl₂). Dose-response studies were conducted on male mice with different groups being injected with 50, 85, and 170 μmol Ni/kg. LPO increased significantly in a dose-dependent manner. In time-course studies, mice were administrated NiCl₂ (170 μmol Ni/kg) and killed at intervals of 6, 12, 24, and 48 h after injection. Both LPO and the accumulation of Ni, Fe, Cu, and Zn in the liver showed a significantly positive time-course relationship after NiCl₂ injection. At 1 h and 24 h after a single ip injection of 170 μmol Ni/kg, the mice were given an ip injection of ascorbic acid (vit C), glutathione (GSH), and selenium (Se). Vit C and GSH significantly decreased both the level of hepatic LPO and the concentration of Ni in the liver, but did not decrease the accumulation of Fe, Cu, and Zn. However, LPO in the experimental group of mice was different significantly from that in the control group. In conclusion, the results suggest that Ni-induced hepatic LPO may result from increasing the amounts of Ni, Fe, and Cu, since these elements are involved in the generation of hydroxyl radical by inducing the Fenton reaction, thus instigating the Ni-mediated hepatic LPO. The protective effects of vit C and GSH in hepatic LPO result not only from removing the oxygen reactive species, but also from decreasing the Ni concentration.     

Effect of nickel chloride on hepatic lipid peroxidation and glutathione concentration in mice

Intraperitoneal administration of nickel chloride enhanced hepatic lipid peroxidation (HLP) in 6-wk-old and 8–12-wk-old male CBA-mice but not in 3-wk-old mice. nickel chloride administration depleted hepatic GSH in 8–12-wk-old mice but not in the younger age groups. After 300 μmol NiCl₂/kg mortality occurred among 8–12-wk-old mice but not among the younger mice. Stimulation of GSH synthesis by administration ofl-2-oxothiazolidine-4-carboxylate reduced nickel chloride induced mortality and HLP. Reduction of GSH synthesis by administration of buthionine sulfoximine (BSO) did not, however, enhance the toxicity of nickel chloride. This might be owing to chelation of the Ni(II)-ion by BSO. The results demonstrate age dependency and a protective effect of enhanced GSH synthesis in nickel chloride stimulated HLP.     

Influence of potassium chloride on alcohol absorption

Simultaneous intragastric administration of large doses of KCl (430 mg/kg and 860 mg/kg) with ethanol (4 g/kg) significantly reduces blood alcohol levels and diminishes manifestations of alcohol intoxication in rats. It was shown with parenteral administration of alcohol that the effect is not related to an acceleration of alcohol metabolism. Analysis of alcohol concentrations of gastric and intestinal content as well as $\text{in situ}$ studies with animals whose stomachs were ligated at the pylorus revealed that KCl interferes with the absorption of alcohol through inhibition of gastric absorption and gastric emptying. The finding that equimolal concentrations of NaCl were unable to duplicate the described effects characterizes them as specific actions of the potassium ion.     

Influence of nitrogen on the behaviour of nickel in wheat

A glasshouse experiment was conducted to study the effect of Ni on the growth and nutrients concentration in wheat (Triticum aestivum Cv. WH 291) in the presence and absence of applied N as urea. Responses to N application were observed up to 120 g N g^–1 soil. No response to Ni was observed in the dry matter yield of wheat tops (leaves + stem) in the absence of applied N while in the presence of applied N, significant yield increases were obtained at 12.5g Ni g^–1 soil. Nickel was not toxic to wheat up to 50g Ni g^–1 soil in the presence of 120g N g^–1 soil. Nitrogen and Ni concentration in wheat tops and roots increased with increasing levels of applied N and Ni, respectively. Applied Ni had an antagonistic effect on N concentration. Similarly, N reduced the Ni concentration in the wheat tissues. Positive growth responses to Ni were associated with 22 and 15g Ni g^–1 in wheat tops, in the presence of applied N at 60 and 120g N g^–1 soil, while Ni toxicity was associated with 63, 92.5 and 112.5g Ni g^–1 in wheat tops, in the absence and presence of applied N at 60 and 120g N g^–1 soil, respectively.     

Chemomodulatory effects of Terminalia chebula against nickel chloride induced oxidative stress and tumor promotion response in male Wistar rats

Nickel, a major environmental pollutant is a known potent nephrotoxic agent. In this communication we report the chemopreventive effect of Terminalia chebula on nickel chloride (NiCl₂) induced renal oxidative stress, toxicity and cell proliferation response in male Wistar rats. Administration of NiCl₂ (250 μmoL Ni/kg body weight) to male Wistar rats resulted in an increase in the reduced renal glutathione content (GSH), glutathione-S-transferase (GST), glutathione reductase (GR), lipid peroxidation (LPO), H₂O₂ generation, blood urea nitrogen (BUN) and serum creatinine with a concomitant decrease in the activity of glutathione peroxidase (p<0.001). Nickel chloride (NiCl₂) treatment also induced tumor promotion markers, viz., ornithine decarboxylase (ODC) activity and thymidine [³H] incorporation into renal DNA (p<0.001). Prophylactic treatment of rats with T. chebula (25 mg/kg body weight and 50 mg/kg body weight) daily for one week resulted in the diminution of NiCl₂ mediated damage as evident from the down regulation of glutathione content, GST, GR, LPO, H₂O₂ generation, BUN, serum creatinine, DNA synthesis (p<0.001) and ODC activity (p<0.01) with concomitant restoration of GPx activity. Thus, the present investigation suggests that T. chebula extract could be used as therapeutic agent for cancer prevention as evident from this study where it blocks or suppresses the events associated with chemical carcinogenesis.     

Comparison of cadmium-induced iron-deficiency responses and genuine iron-deficiency responses in Malus xiaojinensis

The effects of the heavy metal Cd in Malus xiaojinensis were investigated using hydroponic cultures. Chlorophyll and Fe concentrations in young leaves were markedly decreased by Cd treatment, although Fe concentration was significantly enhanced in the roots. A comparative examination of the Fe-deficiency responses due to Fe deficiency and Cd treatment was also performed. Both Fe deficiency and Cd treatment induced responses similar to those of Fe-deficiency in M. xiaojinensis, including acidification of the rhizosphere, enhanced Fe(III) chelate reductase activity, and upregulation of the Fe-deficiency-responsive genes MxIRT1 and MxFRO2-Like. However, the Fe-deficiency responses induced by Cd treatment were different in intensity and timing from those induced by Fe deficiency.     

Assessment of the uptake and mutagenicity of nickel chloride in salmonella tester strains

NiCl2 was examined for mutagenic activity in a number of Salmonella tester strains. Conditions were established where there was substantial uptake of the metal into the bacterial cells. However, even when the metal ion was apparently taken up, as determined by metal association with cells, there was a lack of mutagenic activity. These results suggest that nickel is unable to induce basepair or frameshift mutations in Salmonella tester strains and are discussed in relationship to the low binding affinity of Ni(II) for DNA.     

Effect of lithium chloride on ethanol uptake by rats

A selective uptake of ethanol by presenting its 5% solution as the only source of fluid was elaborated in rats for 2 months. It was found that lithium chloride injected intravenously in a dose of 35 mg/kg twice per 24 hours for 14 days depressed the ethanol preference causing a motivation inversion whose mechanism was associated with the changes in the activity of the hypothalamic centres of the neuroendocrine regulation. A possibility of lithium salts in the therapy of chronic alcoholism is discussed.     

Effect of nickel(II) chloride on iron content in rat organs after oral administration

The effect of oral administration of nickel(II) chloride on iron content in serum and certain body organs of rats was investigated. The male adult rats were given 300 and 1200 ppm Ni in drinking water for 90 d. The iron content in serum, liver, kidney, lung, spleen, and brain was analyzed 30 and 90 d postexposure. The hemoglobin, hematocrit, and body and organ weights were also measured. Nickel given in drinking water led to a pronounced increase in iron content in serum and the liver, as compared to control rats. This effect was related to Ni concentration in the water. There was not great time-dependent difference in the iron content as a response to continuous nickel treatment, except the lung of 1200-ppm Ni-treated rats. In relation to hematological parameters, Ni supplementation did not affect any of them. Body weight significantly decreased, and lung weight was significantly increased in 1200-ppm Ni-treated rats. The results of this study indicate that nickel ingestion (300 and 1200 ppm in the drinking water) induces the iron uptake by serum and some organs of rats. The highest amount of iron was found in the liver of all exposed animals, and the time-dependent difference in iron content was observed in the lung of 1200-ppm Ni-treated rats.