Liver Zinc Levels Research Articles

Effect of sulfite exposure on zinc, iron, and copper levels in rat liver and kidney tissues

Effect of sulfite exposure on zinc, iron, and copper levels in rat liver and kidney tissues

Effects of Vanadium(V) and/or Chromium(III) on L-Ascorbic Acid and Glutathione as well as Iron, Zinc, and Copper Levels in Rat Liver and Kidney

This study investigated the selected parameters of the antioxidant system in liver and kidney after in vivo administration of vanadium and/or chromium in rats. Outbred 2-mo-old albino male Wistar rats received drinking water for 12 wk with either sodium metavanadate (SMV; group II); chromium chloride (Cr; group III); or sodium metavanadate and chromium chloride (SMV-Cr; group IV); and group I (control) received deionized water. Chronic treatment with V alone or in combination with Cr produced a significant increase in kidney relative weight. Further, giving rats V alone also led to a significant elevation in liver relative weight. An increase in hepatic Fe concentration and renal Zn content occurred after treatment with V or Cr, respectively. The rats coadministered V and Cr had significantly higher levels of Fe in liver and Zn in kidneys. Simultaneous administration of these two elements resulted in a significant decrease in renal L-ascorbic acid concentration. V given alone significantly decreased GSH content and GSH/GSSG ratio in liver and kidney as well as increased GSSG concentration in liver, whereas Cr alone produced a significant decrease in GSH content in kidney and GSH/GSSG ratio in both organs. In the SMV-Cr-treated group a significant decrease in renal GSH concentration and GSH/GSSG ratio in both organs occurred. A significant increase in liver GSSG content was also found. The observed significant changes in kidney GSH content and in GSH/GSSG ratio in both rat tissues after Cr might result from the pro-oxidant actions of this metal. Thus, oxidative stress, which is a major pathway for V-induced toxicity, might also be associated with Cr(III)-induced adverse effects in rats.

Effect of Sulfite Exposure on Zinc, Iron, and Copper Levels in Rat Liver and Kidney Tissues

Sulfite is a potentially toxic molecule that might enter the body via ingestion, inhalation, or injection. For cellular detoxification, mammalians rely on sulfite oxidase to convert sulfite to sulfate. The purpose of this research was to determine the effect of sulfite on zinc, iron, and copper levels in rat liver and kidney tissues. Forty normal and sulfite oxidase-deficient male albino rats were divided into four groups that included untreated controls (group C), a sulfite-supplemented group that received 70 mg sodium metabisulfite per kilogram per day (group S), a sulfite oxidase-deficient group (group D), and a sulfite oxidase-deficient group that was also given 70 mg sodium metabisulfite per kilogram per day (group DS). The iron and zinc levels in the liver and kidney in groups S and DS were not affected by sulfite treatment compared to their respective controls (groups C and D). Sulfite exposure led to an increase of kidney copper content in the S group when compared to untreated controls. The kidney copper levels were significantly increased in the unexposed deficient rats, but it was not different than that of the deficient rats that were given oral sulfite treatment. These results suggest that kidney copper levels might be affected by exogenous or endogenous sulfite.

Is tissue copper deficiency associated with aortic aneurysms?

It has been suggested that patients with abdominal aortic aneurysms are deficient in tissue copper. Levels of copper and zinc in liver and aortic wall were therefore measured in 11 patients with aortic aneurysms and 11 fresh cadavers with normal aortas. The concentrations of copper were similar in both groups. Zinc concentration was higher in the normal aortic wall, probably because of the greater thickness of the media in the normal aorta. We found no evidence that aortic aneurysms are associated with reduced tissue copper concentrations.

Possible role of trace elements in the hypoglycemic effect of plants extract in diabetic rats

AbstractThe present study is designed to investigate the possible role of zinc, copper, manganese, and selenium on the hypoglycemic action of a plants mixture and alfalfa using a diabetic rat model. Diabetes was induced in male Wister rats using streptozotocin and confirmed by estimation of glucose levels in blood and urine and further by histologic examination of the pancreas. The animals were treated with the plants mixture and alfalfa extracts orally by gastric intubation for 7 days. Untreated normal and diabetic rats were included as controls. After evaluating glucose tolerance, animals were sacrificed and organs harvested for trace element analysis and histopathological study. The concentration of zinc, copper, manganese, and selenium in plasma, liver, and pancreas of diabetic rats was significantly lower than those of nondiabetic controls. Treatment of diabetic rats with plants mixture and alfalfa significantly decreased the blood glucose concentration but increased the levels of zinc, copper, manganese, and selenium in plasma, liver, and pancreas. Similar changes occurred in the nondiabetic normal control animals treated with the same products. Histological and immunohistochemical examination also confirmed the presence of more β‐cells in the islets of treated diabetic animals compared with untreated diabetic controls. There was no histological evidence of damage to the liver of either diabetic or normal control animals treated with the plants extract. The present study indicated that treatment of diabetes with naturally available plants mixture appears to be effective and the hypoglycemic effect could be through a multimechanism action including that exerted by the trace element content in the different tissues including the pancreas. J. Trace Elem. Exp. Med. 17:31–44, 2004. © 2004 Wiley‐Liss, Inc.

Effect of melatonin treatment on liver and thymus zinc levels in young and middle‐aged rats

AbstractMelatonin (MEL) is the main neurohormone of the pineal gland. Zinc (Zn) is an essential trace element that is required as a catalytic component for more than 200 enzymes. Both MEL and Zn are considered beneficial for anti‐immunosenescence. Recent findings have shown that MEL can modulate Zn turnover. The aim of this study was to investigate the effect of MEL treatment on the tissue Zn levels in young (4 months) and middle‐aged (14 months) rats. Male wistar rats received during 3 weeks subcutaneous injection of MEL (10 mg/kg). After 3 weeks, rats were decapitated and tissue samples were collected. Zn levels were measured by spectrophotometric assay. In conclusion, MEL decreased liver Zn levels both in young and middle‐aged rats. In addition, Zn levels in young control group were significantly higher than middle‐aged control group. However, MEL treatment increased thymus Zn levels in middle‐aged group compared with the control. These findings indicate that tissue Zn levels are significantly affected by MEL treatment. J. Trace Elem. Exp. Med. 17:75–80, 2004. © 2004 Wiley‐Liss, Inc.

Reversal of cadmium induced oxidative stress by chelating agent, antioxidant or their combination in rat

The influence of an antioxidant agent such as N-acetyl cysteine (NAC) or mannitol on the cadmium chelating ability of monoisoamyl 2,3-dimercaptosuccinate (MiADMS) was investigated in cadmium pre-exposed rats. This ester of 2,3-dimercaptosuccinic acid (DMSA), an accepted drug for lead poisoning, being lipophilic in nature was expected to be an efficient cadmium chelator. The treatment of cadmium intoxicated animals with MiADMS reversed cadmium induced increase in blood catalase, superoxide dismutase (SOD) and malondialdehyde (MDA), liver MDA and brain SOD and MDA levels but not the decrease in blood, liver brain reduced glutathione (GSH) and increase in oxidized glutathione (GSSG) levels, consistent with the lowering of tissue cadmium burden. The administration of NAC or mannitol reversed the cadmium induced alterations in blood and liver GSH, GSSG, blood catalase, SOD, MDA, liver SOD, MDA and brain MDA levels without lowering blood and tissue cadmium contents. However, treatments with the combination of MiADMS and NAC or MiADMS and mannitol reversed these alterations as well as reduced blood and tissue cadmium concentrations. The combined treatment with MiADMS and mannitol was better than that with MiADMS and NAC, and was significantly more effective in normalizing blood, liver GSH, GSSG, brain GSSG, and their GSH/GSSG ratios than that by either of them alone. The combined treatments also improved liver and brain endogenous zinc levels, which were decreased due to cadmium toxicity. The results suggest that the administration of an antioxidant during chelation of cadmium may provide beneficial effects by reducing oxidative stress without its cadmium removing ability.

Iron, zinc and copper levels in brain, serum and liver of neonates exposed to 2,4-dichlorophenoxyacetic acid

The effects of 2,4-dichlorophenoxyacetic acid (2,4-D, 70 or 100 mg/kg dam's body weight) on iron (Fe), zinc (Zn) and copper (Cu) in brain, liver and serum of well-nourished and undernourished pups exposed through dam's milk were determined. Undernourishment produced a high Fe decrease (serum and brain) and a delay in weight gain similar to that produced by the highest dose of 2,4-D on well-fed pups. In the latter animals, copper was found to be the most altered ion, increasing its level in serum, liver and some brain areas and decreasing in whole brain. Zinc was the most affected ion in brain areas. Well-nourished pups lactationally exposed to 70 mg 2,4-D/kg dam's body weight altered neither their metal levels nor their body weight in any of the tissues studied. Undernourished pups were more vulnerable to the 2,4-D effect than well-nourished pups. Undernourished pups exposed to a lower 2,4-D dose showed a decrease in their body, brain and liver weight similar to well-fed animals exposed to 100 mg 2,4-D/kg. A noticeable decrease in liver l-tryptophan peroxidase activity by 2,4-D was also registered. This effect was higher in undernourished and 2,4-D-exposed pups. These results suggest that brain areas have a different susceptibility to the herbicide and that undernourishment produces a higher vulnerability to the herbicide and exacerbates the 2,4-D effect.

Metallothionein mRNA levels are influenced by dietary cyclodextrins in rats

The relationship between metallothionein mRNA levels and the amounts of copper and zinc in liver, kidney and small intestine by feeding dietary cyclodextrin was examined in growing Wistar rats. α-, β- or γ-cyclodextrin was fed at 50 g/kg of diet for a 7-days period (ad libitum). After feeding, the liver zinc of rats fed β-cyclodextrin was greater than those of rats fed the other three diets. Copper accumulated in kidney of rats fed α- or β-cyclodextrin. Copper content in the small intestine did not show any alterations among rats fed all kinds of diets. The cyclodextrin-supplemented diets were ineffective in zinc content in every organ. There was the greatest level of copper in serum of rats fed β-cyclodextrin, whereas the highest level of serum zinc was observed in rats fed γ-cyclodextrin diet. Northern blot analysis demonstrated that dietary β- and γ-cyclodextrins, but not α-cyclodextrin markedly increased the metallothionein mRNA in the liver, whereas small intestinal metallothionein mRNA levels were markedly decreased. Kidney metallothionien mRNA levels were raised appreciably by all dietary cyclodextrin intakes. Metallothionein gene expressions in liver, kidney and small intestine were not proportional to liver and serum copper or zinc levels in those tissues. These results suggest that regulation of the metallothionein mRNA levels may at least partly involved with the accumulation of metals as copper in liver and kidney of rats fed cyclodextrins.

Trace metals in tissues of gray whale ( Eschrichtius robustus) carcasses from the Northern Pacific Mexican Coast

Samples of liver, lung, heart, muscle, and blubber tissue from the carcasses of juvenile gray whales ( Eschrichtius robustus) found stranded on the coast off the Sea of Cortez, México were analyzed for a range of trace metals (Cu, Fe, Zn, Mn, Ni, Pb, and Cd). The highest concentrations of copper, iron, zinc, and manganese were found in liver; nickel and lead in heart, and cadmium in kidney. In all tissues analyzed, iron, zinc and copper were present in the highest concentrations; however, some whales also showed high levels of cadmium in the kidney which could be related to their diet. Elevated concentrations of copper were found only in the liver of one whale. In general, where low levels of iron were found in the liver, they were associated with poor nutrition. Lead, nickel, manganese and zinc levels in liver were within the normal range, indicating that these whales had not been exposed to high levels of these metals.

Oxidative stress and metallothionein expression in the liver of rats with severe thermal injury

The aim of this work was to study oxidative stress and the compensating mechanisms implicated in severe thermal injury using the burned rat model. Results showed that after thermal injury glutathione (GSH) level was decreased, oxidized glutathione (GSSG) and the ratio of GSSG/GSH increased both at 24 and 48 h in the liver. The activities of GSH-reductase (GSH-Rx) in the liver and GSH-peroxidase (GSH-Px) both in the liver and erythrocytes increased at 24 h and then decreased at 48 h. The level of α-tocopherol in plasma was reduced at 24 h. Lipid peroxide levels increased both at 24 and 48 h in the liver. The serum zinc level decreased, reaching a minimum at 12 h, whereas liver zinc level was elevated and reached the maximum at 12 h. After severe thermal injury enhancement of metallothionein (MT) expression has been discovered for the first time. MT content in the liver increased both at 24 and 48 h. Expression of MT-I mRNA was activated at 3 h and reached the top at 24 h postburn. The conclusion is that severe thermal injury gives rise to oxidative stress and dramatic enhancement of MT expression could be one of the important compensative mechanisms of natural defense system postburn.

Cadmium, mercury, iron, copper, manganese and zinc in the liver and kidney of the Icelandic lamb

The purpose of this study was to evaluate the levels of cadmium, mercury, iron, copper, manganese and zinc in lamb liver and kidney from six areas in Iceland and to compare the results against aerial deposition data for the same elements obtained using moss as an indicator organism. The total number of samples was 96 for each organ. Cadmium was determined by graphite furnace atomic absorption spectrophotometry, mercury by coldvapour atomic absorption, and iron, copper, manganese and zinc by inductively coupled plasma atomic emission spectrophotometry. Analysis of variance determined significance differences among means for areas, and Pearson's correlation coefficients were calculated to study correlation among trace elements in liver and kidney. The mean fresh weight concentrations in lamb liver and kidney respectively were 0.045 and 0.058mg kg -1 for cadmium, 0.009 and 0.012mgkg-1 for mercury, 141 and 52.7mgkg-1 for iron, 28.1 and 2.89mgkg-1 for copper, 4.01 and 1.13mgkg-1 for manganese and 48.7 and 25.2mgkg-1 for zinc. Concentrations of cadmium, mercury and copper in the liver and kidney of the Icelandic lamb were low compared with data from other countries. Iron concentrations in the organs, however, were high. No sample exceeded 46% of the proposed maximum level for cadmium in organs for human consumption in the EC. Cadmium, mercury, iron and copper in the liver and kidney differed significantly between areas. Deposition of cadmium and copper in moss was not a useful indicator in the evaluation of the susceptibility of the Icelandic lamb to accumulation of cadmium and cop per. However, iron levels in Icelandic lamb liver showed the same pattern as results for iron from the moss study. The cadmium and mercury levels of organs from lambs grazing in the vicinity of Mount Hekla a few months after its eruption did not indicate a significant contamination from volcanic activity.

Zinc and iron bioavailability in a powder or in-bottle-sterilized infant formula estimated by in vitro and in suckling rats

Maillard reaction and lactose isomerization may be induced during the processing involved in the manufacture of infant formulas. The effects of dehydratation and sterilization in an infant formula on iron and zinc bioavailability were studied. A powder (PIF), previously reconstituted, and an in-bottle-sterilized liquid infant formula (LIF), from the same manufacturer, were evaluated using an in vitro method and in suckling rats. After in vitro digestion the dialyzed and non-dialyzed soluble, and insoluble fractions of iron and zinc were separated. Two-week-old rat pups were fed PIF or LIF in a drinking bottle for 7 days. Infant formula intake (I), body weight and the fecal and urinary excretions were monitored and the following parameters calculated: apparent absorption (A), retention (R), and the coefficients %A/I, %R/A and %R/I. Soluble iron (dialyzed) and zinc (non-dialyzed) were higher ( p < 0.001) in LIF than PIF after in vitro digestion. Insoluble iron was similar in both infant formulas but insoluble zinc was lower ( p < 0.05) in LIF than PIF. Food intake ( p = 0.045) and body weight on day 4 ( p < 0.05) and on day 7 ( p < 0.001) were lower in LIF compared to PIF. A, R ( p < 0.05 for both minerals), %A/I, and %R/I ( p < 0.001 and p < 0.05 for iron and zinc, respectively) were significantly lower in rats fed LIF. Similarly, the %R/A of iron was lower ( p < 0.001) in this group. Hematocrit and hemoglobin did not show significant differences. Iron and zinc levels in liver, spleen and erythrocytes were similar in both groups, but skin iron concentration was higher in LIF. Therefore, in contrast with the in vitro results, consumption of the in-bottle-sterilized formula determines lower iron and zinc bioavailability compared to the reconstituted powder infant formula.

Elements in autopsy liver tissue samples from Greenlandic Inuit and Danes. III. zinc measured by X-ray fluorescence spectrometry

The aim of the study was to measure the content of zinc (Zn) in liver tissue samples from Greenlandic Inuit using X-ray fluorescence spectrometry, and compare the results with those obtained in liver samples from Danes. Normal liver tissue samples was obtained at autopsy from 50 Greenlandic Inuit (27 men) with a median age of 61 years (range 23–83) and from 74 Danes (44 men) with a median age of 60 years (range 15–87). In the entire series, liver zinc content in Inuit was not significantly different compared with Danes. There was no significant gender difference in liver zinc content either in Inuit or in Danes. The content of zinc given as median (5–95 percentile) was in Inuit 3.809 mmol/kg dry liver (2.355–7.406), and in Danes 3.992 mmol/kg dry liver (2.499–8.645). There was a significant, positive correlation between liver zinc content and age in Danish women (rs = 0.43, p = 0.02), which could not be demonstrated in Danish men or in Inuit. Median hepatic zinc index (zinc content in mmol/kg dry weight divided by age in years) in Inuit was 0.073, and in Danes 0.080 (p = 0.3) without any significant difference between the two genders. In Inuit and Danes there was an inverse correlation between hepatic zinc index and age both in the two genders and in the entire series: Inuit: rs = −0.62, p < 0.0001; Danes: rs = −0.70, p < 0.0001. The results indicate that Inuit have liver zinc levels, which are similar to those found in Danes.

Zinc supplementation prevents liver injury in chlorpyrifos-treated rats.

The present study was performed to investigate the protective effects of zinc (227 mg/L in drinking water) treatment in chlorpyrifos (13.5 mg/kg body weight, orally) induced hepatotoxicity in male rats. Animals received chlorpyrifos and/or zinc treatments for 8 wk. A 99mTc-mebrofenin clearance test was done to determine the biological half-life (Tbiol) of the radiopharmaceutical in liver for the determination of the hepatobiliary function of the animals. At the end of treatment periods, samples were collected for the measurement of zinc levels in serum and liver. Electron microscopic studies were performed to study hepatic ultrastructure following various treatments. When compared to normal controls, chlorpyrifos treatment resulted in reduced hepatic and serum zinc levels (p < 0.01). The biological half-life (Tbiol) of 99mTc-mebrofenin in liver was increased (p < 0.01) significantly in chlorpyrifos-treated animals, reflecting a poor excretion of the radiopharmaceutical from the liver. Simultaneous zinc supplementation retained the increased hepatic Tbiol values of 99mTc-mebrofenin within normal limits. Zinc treatment also protected hepatocytes from the marked disruptions in the membranous organelles and narrowing/blocking of biliary channels, which was otherwise a common observation following chlorpyrifos treatment. These data clearly show the protective effects of zinc in animals subjected to organophosphate poisoning.

Hepatic Zinc Response via Metallothionein Induction after Tumor Transplantation

Based on previous findings that liver zinc and metallothionein (MT) levels increase after tumor transplantation, zinc metabolism in tumor-bearing mice was studied to clarify the role of zinc–MT in host defense systems. Zinc in the hepatic cytosolic MT fraction did not increase in tumor-bearing mice fed a zinc-deficient diet, suggesting that dietary zinc is necessary for apo-MT induction in the liver after tumor transplantation and is then incorporated into the apo-MT. When 65ZnCl2 was intravenously injected, liver 65Zn levels in the tumor-bearing mice were higher than those in control mice for 72 h after the injection. Pancreatic and blood 65Zn levels in tumor-bearing mice were lower than those in controls for 24 h (pancreas) and 6 h (blood) after the injection. These findings indicate that the hepatic zinc response via MT induction influences zinc metabolism in the body after tumor transplantation. Moreover, 65Zn uptake in the liver of MT-deficient tumor-bearing mice was lower than that in control tumor-bearing mice 1 h after injection. 65Zn uptake in the tumor and blood 65Zn levels in the MT-deficient tumor-bearing mice were higher than those in the control tumor-bearing mice. Tumor weight increased more in MT-deficient mice than in control mice. The formation of zinc–MT in the liver of tumor-bearing mice might decrease blood zinc availability for tumors and other tissues, such as the pancreas.

Effect of surgically induced cholestasis on the levels of hepatic zinc and metallothionein in rat liver.

Early effects of experimental cholestasis on the homeostasis of zinc (Zn) and metallothionein (MT) were studied in rats which had undergone bile duct ligation for 0, 3, 6, 9, 12, 16, 20, and 24 h. Transient increases in hepatic Zn levels were observed at 9 h but returned to control values at 12 h. Serum Zn levels increased at 24 h. Cholestasis was confirmed by increased serum alkaline phosphatase (AP) activity. MT increased at 3 h and reached a maximum level at 12 h and remained elevated even at 24 h after the onset of experimental cholestasis. No hepatocellular damage was detected according to the results of alanine aminotransferase (ALT) activities in serum. These results shown that the increases in Zn observed in liver are related to bile stagnation rather than to a hepatocellular damage and that increased MT occurs concurrently with increased hepatic Zn. These observations suggest that the cellular levels of Zn in cholestasis is regulated by homeostatic mechanisms, of which one could be mediated by MT.

Prophylactic effect of melatonin on lead-induced inhibition of heme biosynthesis and deterioration of antioxidant systems in male rats.

We studied the protective role of the pineal hormone melatonin on lead-induced suppression of the heme synthesis pathway as a consequence of reduced antioxidant systems in rat. We injected rats intramuscularly with lead acetate (10 mg/kg body weight) daily for 7 days, which significantly abolished heme synthesis as evidenced by decreased blood hemoglobin, liver delta-aminolevulinic acid synthetase, erythrocytic delta-aminolevulinic acid dehydratase, and hepatic iron content. These effects were accompanied with marked elevation of hepatic lipid peroxidation and decreased enzymatic antioxidants such as glutathione reductase, glutathione-S-transferase, superoxide dismutase, and catalase, as well as nonenzymatic antioxidants such as total sulfhydryl groups and glutathione. Furthermore, lead treatment caused hepatic deficiency in copper and zinc accompanied by a significant elevation of lead concentration in both plasma and liver. Daily pretreatment with melatonin (30 mg/kg body weight) intragastrically prevented the suppressive effects of lead on heme-synthesizing enzymes and iron deficiency. In addition, preadministration of melatonin reduced the inhibitory effect of lead on both enzymatic and nonenzymatic antioxidants. This was accompanied by marked normalization of lipid peroxidation and modulation of copper and zinc levels in liver. The action of melatonin on lead-induced changes was attributed to protection of the antioxidant capacity in cells in addition to the ability of melatonin to scavenge free radicals.

Paracetamol hepatotoxicity in metallothionein-null mice

The role of metallothionein (MT) in protecting the liver against paracetamol (PCT) toxicity was investigated in vivo and in vitro in mice lacking expression of MT−1 and MT−2 genes (MT−/−). In the fed, glycogen replete state, hepatotoxicity (PCT 300 mg/kg i.p.) at 6 h was significantly greater in MT−/− than MT+/+ mice. Plasma lactate dehydrogenase (LD) and alanine aminotransferase (ALT) were 5- and 13-fold greater respectively than in MT+/+ mice. Liver glycogen, glucose and zinc levels were significantly lower in MT−/− mice at this time. In contrast, hepatotoxicity (PCT 135 mg/kg i.p.) at 6 h was similar in both MT+/+ and MT−/− mice fasted 24 h, despite a doubling in liver MT in MT+/+ mice. No differences were found between MT−/− and MT+/+ mice in cytochrome P450 activity. Liver glutathione levels were the same in both groups of mice prior to fasting and were decreased to a similar extent (55–65%) following PCT treatment. Investigation of lower PCT doses (≤120 mg/kg) in fasted mice over 24 h demonstrated a greater susceptibility in female MT−/− mice with plasma LD, 2.4-fold and ALT, 7.5-fold greater than in MT +/+ mice at 120 mg/kg PCT. In male MT−/− mice, there was only a trend towards greater susceptibility at 110 mg/kg PCT compared to male MT+/+ mice, and at 120 mg/kg, both male genotypes were equally affected. Investigations with cultured hepatocytes supported the in vivo findings in that there was a trend towards greater toxicity (PCT at 1 and 5 mM for 24 h) in hepatocytes from fed MT−/− mice, with the difference diminished in association with greater hepatotoxicity in hepatocytes from fasted mice. Use of dexamethasone (Dex) to increase MT in the MT+/+ mouse hepatocytes protected from PCT toxicity. Zn alone was not protective. Zn plus Dex offered no protection despite higher MT levels. Generation of apo-MT with Dex may offer more protection than Zn-MT. In conclusion, MT−/− mice were more susceptible than MT+/+ mice to PCT toxicity in the fed state, but the increased susceptibility was much smaller, but still significant, when the effects of glycogen were minimised by fasting.

Alterations in Total Iron, Zinc, and Calcium Levels and Their Influence on the Hepatic Activities of Gamma-glutamyl Transferase and Glucose-6-phosphatase in the Host Bearing Transplantable Murine Lymphoma

The levels of iron, zinc, and calcium in liver as well as serum, together with the enzymatic activities of γ-glutamyl transferase (GGT, EC 2.3.2.2) and glucose-6-phosphatase (G-6-Pase, EC 3.1.3.9) in liver, were critically monitored over various periods in male Swiss albino mice bearing Dalton's lymphoma (DL), a transplantable ascites-producing tumor. Both hepatic and serum contents of iron, zinc, and calcium were found to be maximally elevated (p < 0.001) on day 15 after tumor transplantation as compared with their contents in normal animals. There was a gradual increase in the activity of GGT in liver in lymphoma-bearing mice in comparison with their normal counterparts, which showed a maximum peak (p < 0.001) on day 15, followed by a continuous and sharp fall. Hepatic G-6-Pase activity was found to decrease continuously throughout the progression of lymphoma as compared with its levels to normal animals. Tumor-cell counts in peritoneal lymph fluids of mice containing DL yielded a maximum count of 155.7 × 103 cells/mm3 on day 15. A significant correlation was observed among the levels of different metals, enzymatic activities, and tumor-cell counts at different periods of study. From these results, it can be concluded that the metals studied may have a role in initiating and controlling cellular proliferations, through their effects on modulating the activities of the possibly preneoplastic and neoplastic marker enzymes named above.