Zinc sulphate following the administration of iodine-131 on the regulation of thyroid function, in rats.

Hyperthyroidism in men is often treated with high doses of iodine-131 ((131)I), which may induce radiation side effects to patients and their environment. These therapeutic doses of (131)I could be decreased, if the (131)I uptake of the thyroid gland of the patients could be increased. Zinc sulphate has been considered to exercise a protective role by maintaining the cellular integrity of the thyroid under various pathological states. The aim of our study was to study in Wistar rats whether zinc sulphate can after treatment of the thyroid gland with (131)I: a) increase the uptake of (131)I in the thyroid and b) stabilize the function of the follicular cells. If such a stabilization finally exists in men we could have favorable results like fewer cases of hypothyroidism after (131)I treatment of hyperthyroidism. To carry out these investigations, rats were divided into four groups comprising of eight animals each. Group I animals served as normal controls. Group II animals received a dose of 3.7 MBq of (131)I. Group III animals were supplemented with zinc (227 mg/L of drinking water) and animals in Group IV were given (131)I together with zinc sulphate as above. Our results showed that in Group II, serum levels of tetra-iodo-thyronine (T(4)) and tri-iodo-thyronine (T(3)) decreased significantly as a function of time following (131)I treatment. An increase in the levels of serum thyroid stimulating hormone (TSH) was noticed one week after (131)I treatment, becoming less pronounced with time. In Group II, thyroid uptake at 2h and at 24h was significantly decreased. In the same Group biological half life (T(biol)) of (131)I in the thyroid gland, was significantly elevated four weeks after the administration of (131)I and decreased eight weeks after. In Group IV animals, zinc sulfate after four weeks, induced normalization of elevated serum TSH levels and a further increase in the T(biol) of (131)I. After eight weeks in these animals, serum T(3) became normal and TSH remained at normal levels. Thyroid (131)I uptake at 2 and 24 h was increased as compared to Group II. Group III animals showed some increase in the levels of Na(+)K(+)ATPase and type 1,5'-deiodinase (5'-DI) as compared to normal rats of Group I. In conclusion, this study suggests the protective potential of zinc sulphate in the disturbed after (131)I treatment, thyroid function, thyroid hormones and TSH while the (131)I uptake was reduced. Thus, if this result is further confirmed, zinc sulphate may show to be a promising radioprotective agent for the thyroid gland.

131I induced hematological alterations in rat blood: protection by zinc.

The present study was planned to determine the potential of zinc in attenuating the toxicity induced by 131I in rat blood. Female wistar rats were segregated into four main groups. Animals in Group I served as normal controls; Group II animals were administered a dose of 3.7 Mbq of 131I (carrier free) intraperitoneally, Group III was supplemented with Zinc in the form of ZnSo4.7H2O (227 mg/l drinking water), and Group IV was given a combined treatment of Zinc as well as 131I, in a similar way as was given to Groups IV and II animals, respectively. The effects of different treatments were studied on various parameters in rat blood including hemoglobin (Hb) levels, % hematocrit, zinc protoporphyrins (ZPP), activities of enzymes which included aminolevulinic acid dehydratase (delta-ALAD) and Na+ K+ ATPase and uptake of 65Zn in blood. The study revealed an increase in the levels of hemoglobin, % hematocrit, activities of delta-ALAD, Na+ K+ ATPase and uptake of 65Zn, 7 days after the 131I treatment. On the contrary, the levels of ZPP were found to be significantly decreased after 131I treatment. However, zinc treatment to 131I-treated animals significantly attenuated the various biochemical and hematological indices. Moreover, zinc treatment to the 131I-treated animals could significantly decrease the uptake of 65Zn, which was increased after 131I treatment. Based upon these data, the present study suggests that zinc has the potential to attenuate 131I induced toxicity by restoring the altered hematological indices and biochemical changes.

Chemopreventive potential of zinc in experimentally induced colon carcinogenesis.

The present study was performed to evaluate the efficacy of zinc treatment on colonic antioxidant defense system and histoarchitecture in 1,2-dimethylhydrazine- (DMH) induced colon carcinogenesis in male Sprague-Dawley rats. The rats were segregated into four groups viz., normal control, DMH treated, zinc treated, DMH+zinc treated. Colon carcinogenesis was induced through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 16 weeks. Zinc (in the form of zinc sulphate) was supplemented to rats at a dose level of 227 mg/L in drinking water, ad libitum for the entire duration of the study. Increased tumor incidence, tumor size and number of aberrant crypt foci (ACF) were accompanied by a decrease in lipid peroxidation, glutathione-S-transferase, superoxide dismutase (SOD) and catalase. On the contrary, significantly increased levels of reduced glutathione (GSH) and glutathione reductase (GR) were observed in DMH treated rats. Administration of zinc to DMH treated rats significantly decreased the tumor incidence, tumor size and aberrant crypt foci number with simultaneous enhancement of lipid peroxidation, SOD, catalase and glutathione-S-transferase. Further, the levels of GSH and GR were also decreased following zinc supplementation to DMH treated rats. Well-differentiated signs of dysplasia were evident in colonic tissue sections by DMH administration alone. However, zinc treatment to DMH treated rats greatly restored normalcy in the colonic histoarchitecture, with no apparent signs of neoplasia. EDXRF studies revealed a significant decrease in tissue concentrations of zinc in the colon following DMH treatment, which upon zinc supplementation were recovered to near normal levels. In conclusion, the results of this study suggest that zinc has a positive beneficial effect against chemically induced colonic preneoplastic progression in rats induced by DMH.

Zinc mediates normalization of hepatic drug metabolizing enzymes in chlorpyrifos-induced toxicity.

The present study investigated the protective effects of zinc in attenuating the altered activities of drug metabolizing enzymes in the livers of rats intoxicated with chlorpyrifos. Male Sprague-Dawley rats received oral chlorpyrifos treatment (at a dose level of 13.5 mg/kg body weight in corn oil every alternate day), zinc supplementation alone (at a dose level of 227 mg/l in drinking water), or combined chlorpyrifos plus zinc treatments for a total duration of 8 weeks. The effects of different treatments were studied on the specific activities of various drug metabolizing enzymes including cytochrome P(450), cytochrome b(5), NADPH cytochrome-c-reductase, NADH cytochrome-c-reductase, aminopyrene-N-demethylase (APD) and aromatic hydrocarbon hydroxylase (AHH). Additionally, serum zinc levels were also determined in each of the treatment groups at the end of the study. Chlorpyrifos treatment resulted in a significant decrease in the serum zinc concentrations. Analogous to these changes, we observed significant depression in the activities of majority of the drug metabolizing enzymes investigated in the present study, except for AHH, where the decrease in enzyme activity was not statistically significant. However, zinc treatment to chlorpyrifos treated animals effectively restored the depressed serum zinc levels to within normal limits. Similarly, co-administration of zinc to chlorpyrifos intoxicated animals normalized the enzymatic activities of cytochrome P(450), NADPH cytochrome-c-reductase and NADH cytochrome-c-reductase within normal range. Collectively, these findings suggest that zinc plays an important role in regulating the hepatic activities of drug metabolizing enzymes in chlorpyrifos intoxicated animals, although it remains to be determined whether such protective effects of zinc are regulated directly, or through some indirect mechanism.

Role of zinc in mitigating the toxic effects of chlorpyrifos on hematological alterations and electron microscopic observations in rat blood.

The present study determined the protective potential of zinc in attenuating the toxicity induced by chlorpyrifos in rat blood. Male Sparque Dawley (SD) rats received either oral chlorpyrifos (13.5 mg/kg body weight) treatment every alternate day, zinc alone (227 mg/l in drinking water) or combined chlorpyrifos plus zinc treatment for a total duration of 8 weeks. The effects of different treatments were studied on various parameters in rat blood including haemoglobin (Hb) levels, total leukocyte count (TLC), differential leukocyte count (DLC), zinc protoporphyrins (ZPP), serum trace elemental concentrations and Scanning Electron Microscopic (SEM) observation of the blood cells. Chlorpyrifos treatment to normal control animals resulted in a significant decrease in TLC and ZPP concentration after 4 and 8 weeks. Chlorpyrifos treated animals also showed significant neutrophilia and lymphopenia after 8 weeks of toxicity. In addition, a significant decrease in serum zinc and iron concentrations were observed following chlorpyrifos intoxication, however, these animals responded with increased serum copper levels following the toxic treatment with this organophosphate. SEM studies of the red blood cells from chlorpyrifos treated animals indicated marked alterations in the topographical morphology of the various cell types, with the prominent feature being common aniscocytosis of the erythrocytes. Oral zinc treatment to the chlorpyrifos treated animals significantly improved the total leukocyte, neutrophil and lymphocyte counts, as well as the otherwise reduced concentrations of ZPP and the levels of various serum trace elements. Protective effects of zinc were also evident in the electron microscopic observations where most blood cell types depicted reverted to a close to the normal appearance. Based upon these data, the present study is first of its kind and suggests that zinc treatment considerably attenuates chlorpyrifos induced toxicity induced in restoring the altered hematological indices and morphological changes.

Zinc as an antiperoxidative agent following iodine-131 induced changes on the antioxidant system and on the morphology of red blood cells in rats.

Iodine-131 ((131)I) irradiation is the first line treatment for Graves' disease and thyroid carcinoma. In such cases, (131)I gets accumulated in the thyroid, and is released in the form of radioiodinated triiodothyronine (T3) and tetraiodothronine (T4). Various reports describe changes in the blood picture after radioiodine treatment. Zinc, on the other hand, has been reported to maintain the integrity of red blood cells (RBC) under certain toxic conditions. The present study was conducted to evaluate the adverse effects of (131)I on the antioxidant defense system and morphology of RBC and also to assess the possible protection by zinc under irradiation by (131)I. Thirty two female Wistar rats were equally segregated into four main groups. Animals with Group I served as normal controls; Group II animals were administered a dose of 3.7 MBq of (131)I (carrier free) intraperitoneally, Group III rats were supplemented with zinc (227 mg/L drinking water) and Group IV rats were given a combined treatment of (131)I and zinc, in a similar way as in Group II and IV rats. After seven days of (131)I treatment, RBC lysate was prepared and its antioxidant status assessed. The activity of superoxide dismutase (SOD), reduced glutathione (GSH) and malondialdehyde (MDA) in the lysate of RBC was increased. On the contrary, the activity of catalase was found to be significantly decreased. The activity of glutathione reductase (GR) remained unchanged. Marked changes in the shape of RBC from normal discocytes to echinocytes, spherocytes, stomatocytes and acanthocytes were also observed in the blood of the rats treated with (131)I. Zinc supplementation to (131)I treated rats, significantly attenuated the adverse effects caused by (131)I on the levels of MDA, GSH, SOD and catalase. In conclusion, the study revealed significant oxidant/antioxidant changes in RBC following (131)I administration in rats, while zinc was shown to act as a radioprotector agent.

Hepatoprotective role of zinc in lead-treated, protein-deficient rats.

The current study was designed to evaluate the hepatoprotective role of zinc after lead (Pb) treatment of protein-deficient (PD) rats. The animals were subjected to seven different treatment groups: G-1 (normal control, 18% protein), G-2 (protein-deficient, 8% protein), G-3 (Pb-treated, 100 mg/kg body weight of lead acetate), G-4 (Zn-treated, zinc sulfate at a dose level of 227 mg/L drinking water), G-5 (PD + Pb-treated), G-6 (PD + Zn-treated), and G-7 (PD + Pb + Zn-treated). Serum albumin levels and total serum protein contents were estimated to assess the severity of protein deficiency at the end of 8 weeks in all the treatment groups. Also, the study explored the role of zinc on antioxidative defense system enzymes in liver of protein-deficient rats subjected to lead toxicity treatment. Further, the study was extended to elucidate the levels of zinc and lead in liver tissue after different treatments of rats using positron-induced X-ray emission technique (PIXE). The current study indicated a significant change in the levels of various antioxidative enzymes and serum albumin as well as total protein contents of protein-deficient rats subjected to lead treatment. A significant increase in the levels of malondialdehyde (MDA), catalase, and glutathione peroxidase (GPx) was seen after 8 weeks of lead treatment of protein-deficient rats. On the contrary, levels of albumin, total protein content, superoxide dismutase (SOD), GSH, were found to be decreased. Interestingly, zinc supplementation has tended to normalize the altered levels of these enzymes to a significant extent. The levels of zinc in liver tissue was found to be decreased significantly in protein-deficient as well as lead-treated rats. However, hepatic zinc concentration was increased to a significant extent in protein-deficient rats supplemented with zinc when compared with protein-deficient rats. Further, the presence of lead was also observed in livers of lead-treated animals. In conclusion, the study revealed the antioxidative role of zinc in hepatotoxic conditions induced by subjecting the rats to protein-deficient diet and lead treatment.

Chlorpyrifos-induced alterations in the activities of carbohydrate metabolizing enzymes in rat liver: the role of zinc.

The present study was conducted to evaluate the adverse effects of chlorpyrifos on the key enzymes of carbohydrate metabolism in liver, and also to assess the role of zinc under these toxic conditions. Male Sprague-Dawley (SD) rats received either oral chlorpyrifos treatment (13.5 mg/kg body weight in corn oil) every alternate day, zinc alone (227 mg/l in drinking water), or combined chlorpyrifos and zinc treatments for a total duration of 8 weeks. The effects of different treatment regimens were studied on various enzymes of carbohydrate metabolism in the rat livers, which included hexokinase, glucose-6-phosphatase, fructose-1,6-diphosphatase, glycogen phosphorylase, succinate dehydrogenase (SDH), lactate dehydrogenase (LDH) and the levels of glycogen. In vitro uptake of (14)C-D-glucose was also assessed in liver slices after similar treatments. Chlorpyrifos intoxication resulted in a significant increase in the activities of glucose-6-phosphatase and glycogen phosphorylase, whereas, it caused a significant inhibition in the levels of hexokinase, SDH, LDH and glycogen content. However, zinc treatment to chlorpyrifos-intoxicated animals was able to normalize the activities of most of these enzymes to either close to, or within normal limits. Chlorpyrifos intoxication demonstrated significantly inhibited (14)C-D-glucose uptake in liver slices, which again was reversed to normal limits following simultaneous zinc treatment. Levels of metallothionein were also found to be depressed in chlorpyrifos-treated animals, but tended to increase significantly on co-administration of zinc to chlorpyrifos-treated group. Hence, the present study clearly suggests that zinc plays an important role in regulating the hepatic activities of the enzymes involved in carbohydrate metabolism under conditions of chlorpyrifos toxicity.

Effectiveness of Zinc in Modulating the CCl (4) - Induced Oxidative Stress in Rat Liver.

The present study was designed to evaluate the role of zinc on the enzymes involved in oxidative defense mechanism in conditions of carbon tetrachloride (CCl (4)) -induced rat liver toxicity. To carry out the study, rats were divided into four groups: group I (normal control), group II (CCl (4) treated), group III (zinc control), and group IV (zinc + CCl (4) treated). Animals in group II and group IV were administered 0.1 mL of CCl (4) mixed with 0.1 mL of groundnut oil on alternate days for a period of 8 weeks. Zinc in the form of zinc sulphate was given to animals of group II and group IV at a dose level of 227 mg/L in drinking water. Animals given CCl (4) treatment alone showed a significant increase in the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and the concentration of malondialdehyde (MDA) product, whereas a significant depression was observed in the levels of reduced glutathione (GSH). Zinc treatment to CCl (4) -treated rats brought the altered levels of GSH, MDA, and SOD as observed following CCl (4) -treatment alone to within normal limits. However, the activities of catalase and glutathione peroxidase, which were increased under carbon tetrachloride treatment, were significantly attenuated and tended to become normal. Hence, the present study suggests that zinc may play an important role in regulating the activities of the enzymes involved in antioxidative defense system under CCl (4) toxic conditions.

Protective effects of zinc on lipid peroxidation, antioxidant enzymes and hepatic histoarchitecture in chlorpyrifos-induced toxicity.

The present study investigated the hepatoprotective role of zinc in attenuating the toxicity induced by chlorpyrifos in rat liver. Male Sprague-Dawley (SD) rats received either oral chlorpyrifos (13.5mg/kg body weight), zinc alone (227mg/l in drinking water) or combined chlorpyrifos plus zinc treatment for a total duration of 8 weeks. The effects of these treatments were studied on various parameters in rat liver, including lipid peroxidation, antioxidant enzymes, levels of metallothionein (MT) and hepatic histoarchitecture. Chlorpyrifos treatment resulted in a significant increase in hepatic lipid peroxidation and activities of superoxide dismutase (SOD), glutathione peroxidase (G-Px) and glutathione reductase (GR). On the contrary, chlorpyrifos intoxication caused a significant inhibition in the levels of reduced glutathione (GSH), catalase (CAT) and glutathione-S-transferase (GST) activities. However, zinc treatment to chlorpyrifos-intoxicated animals normalized the otherwise raised levels of lipid peroxidation to within normal limits. Moreover, zinc treatment to these animals resulted in an elevation in the levels of GSH, catalase and GST, as well as a significant decrease in the levels of SOD. Levels of MT were also found to be depressed in chlorpyrifos-treated animals, but tended to increase following co-administration of zinc. Additionally, chlorpyrifos-treated animals demonstrated increased vacuolization, necrosis and ballooning of the hepatocytes and dilatation of sinusoids as well as increase in the number of binucleated cells. However, zinc administration to chlorpyrifos-treated animals resulted in overall improvement in the hepatic histoarchitecture, emphasizing the protective potential of zinc. Hence, the present study suggests the protective potential of zinc in alleviating the hepatic toxicity induced by chlorpyrifos.

The influence of lithium on biokinetics and biodistribution of 65Zn under different dietary protein regimens in rats.

The present study was designed to evaluate the effect of lithium on the biological half-lives of 65Zn in the rat liver and whole body and also its biodistribution under different dietary protein regimens. To carry out these investigations, each rat after three weeks of different treatments was injected with 1.85 MBq of 65Zn, intraperitoneally (ip) and its radioactivity was recorded in liver as well as in whole body by using gamma ray spectrometer. The radionuclide 65Zn showed two kinetic components indicating its biological half-life: Tb1 the initial fast component and the Tb2 or slow component. Protein deficiency led to a significant elevation of both components in the whole body but not in the liver when compared to the control group. High protein (HP) diet in rats resulted in marked reduction in both components in the liver but not in the whole body. Lithium treatment alone to normal rats caused a significant reduction in the Tb2 but not in the Tb1 component in the whole body as well as in the liver. The administration of lithium normalized the observed increase in both components in the whole body of protein deficient rats. On the contrary, in rats fed with low protein (LP) diet after lithium treatment the Tb(2) component was significantly reduced in the liver. Lithium treatment to HP fed rats, showed a significant decrease in both components in the liver when compared to normal rats: however this decrease was less pronounced in comparison to the HP group that had not been given lithium. Furthermore, one day prior to the end of the treatment period, the rats were injected ip with a tracer dose of 0.37 MBq 65Zn and 24 h later, various organs were excised for 65Zn biodistribution measurements in vitro. Under different dietary protein regimens as well as after administration of lithium the percent uptake values of 65Zn varied in various organs viz: the brain, liver, kidney, small intestine and large intestine as well as in the blood. In conclusion, different protein dietary conditions on co-administration with lithium in the rats seemed to have a dominant role for the retention of 65Zn in the liver the whole body and in other organs.

Influence of zinc on the status of hepatic trace elements and biokinetics of 65Zn in ethanol treated rats.

Whole body counting studies of 65Zn indicated that the Tb1 (the faster component) was significantly decreased while the slower component (Tb2) was increased significantly following ethanol treatment. Interestingly, following zinc treatment to ethanol treated rats, slower component (Tb2) of 65Zn came back to within normal limits while the faster component (Tb1) got significantly elevated in comparison to ethanol treatment. Percent uptake values of 65Zn were found to be increased in liver, intestine, muscle, brain and kidney, and decreased in bone under alcoholic conditions. Interestingly, the uptake values of 65Zn in all the organs except muscle were reverted back to within normal limits upon zinc supplementation to these ethanol intoxicated animals. A significant decrease in zinc contents was noticed in ethanol treated rats, which, however, were raised to normal levels upon zinc supplementation: Copper levels, on the other hand, were significantly enhanced in both ethanol fed and combined ethanol + zinc treated rats. Calcium levels were significantly decreased in both ethanol and zinc treated rats, which however were further reduced upon zinc supplementation to ethanol fed rats. However, no significant change was observed in the concentrations of sodium and potassium in any of the treatment groups. In conclusion, zinc appears to play a protective role by normalizing the turnover of 65Zn in whole body as well as in its uptake in different organs under alcoholic conditions.

Radioprotective role of zinc following single dose radioiodine (131I) exposure to red blood cells of rats.

BACKGROUND & OBJECTIVES: Irradiation with 131I is used for the treatment of various thyroid disorders. It is likely that radioiodine while in systemic circulation may cause some adverse effects on antioxidative enzymes present in red blood cells (RBCs). Zinc, on the other hand, has been reported to maintain the integrity of cells under certain toxic conditions. The present study was conducted to evaluate the adverse effects of 131I on RBCs and also to assess the protection provided by zinc under these conditions. METHODS: Female Wistar rats (n=32) were divided into four groups. Animals in group I served as normal controls; group II animals were administered a dose of 3.7 Mbq of 131I (carrier-free) intraperitoneally, group III animals were supplemented with zinc (227 mg/l drinking water) and animals in group IV were given a combined treatment of zinc as well as 131I. Activities of antioxidant enzymes were assessed in erythrocyte lysates after two days of treatments. RESULTS: An increase in the activity of glutathione reductase (GR), superoxide dismutase (SOD), reduced glutathione (GSH) and malondialdehyde (MDA) in the lysates of erythrocytes was seen after two days of exposure from 131I radiations. However, the activity of catalase was found to be significantly decreased. Interestingly, zinc supplementation to 131I treated rats resulted in attenuating the adverse effects caused by 131I on the levels of antioxidative enzymes. INTERPRETATION & CONCLUSION: 131I can induce significant oxidant/antioxidant changes in RBCs and zinc may prove to be a candidate with great promise for radioprotection.