Uptake and turnover of65Zn in subcellular fractions of brain of rat under normal and zinc-deficient conditions

After a single injection,⁶⁵Zn is slowly taken up by the brain of the rat to a maximum after 7 d, followed by a turnover phase, with a half-time of about 3 wk. In the brain of rats on a zinc-deficient diet, the⁶⁵Zn content in the brain continued to increase up to 30 d after the injection. The uptake and turnover phases in six different subcellular fractions of the brain showed a pattern similar to that of the whole brain in both the control and zinc-deficient rats. There was no internal redistribution of⁶⁵Zn in the brain under conditions of progressive zinc deficiency. The results are discussed in a model for zinc homeostasis in the brain.     

Cultured human skin fibroblasts absorb65Zn

The radioactive isotope⁶⁵Zn was used to study the incorporation of zinc by cultured human skin fibroblasts. The development of the method for studying cell uptake of⁶⁵Zn in a minimal synthetic medium is presented. Kinetics carried out on control cultures up to 240 min indicated that zinc uptake occurred in three phases, the first being the most rapid. Temperature and pH affect zinc uptake, in favor of an active transport process. In addition, the rate of incorporation is considerably decreased during the first phases after adding potassium cyanide, during the last phases after adding sodium iodoacetate, and during all the phases if dithioerythritol is used. A hypothesis is therefore proposed according to which several types of mechanisms would be involved in zinc uptake by fibroblasts. At least a part of these mechanisms is energy-dependent.     

Effect of zinc on biological half-lives of 65Zn in whole body and liver and on distribution of 65Zn in different organs of rats following nickel toxicity

This study was designed to determine the effect of zinc on the biological half-lives of ⁶⁵Zn in whole body and liver and on distribution of ⁶⁵Zn in different organs of rats following nickel toxicity. Sprague-Dawley (SD) rats received either nickel in the form NiSO₄·6H₂O at a dose of 800 mg/L in drinking water, zinc in the form of ZnSO₄·7H₂O at a dose of 227 mg/L in drinking water, and nickel plus zinc or drinking water alone for a total duration of 8 wk. All of the rats were injected with a tracer dose of 0.37 MBq ⁶⁵Zn at the end of the treatment period. The effects of different treatments were studied on biological half-lives of ⁶⁵Zn in whole body and liver and on the distribution of ⁶⁵Zn in different organs of rats. In the present study, we have noted that nickel treatment to normal rats caused a significant decrease in the slow component (Tb₂) in liver, which improved following zinc supplementation. Nickel administration to normal-diet-fed animals caused significant lowering in the percentage uptake of ⁶⁵Zn values in the brain, liver, and intestine. However, the administration of zinc to nickel-treated rats improved the status of ⁶⁵Zn in different organs. The Tb₂ in the liver and the percentage uptake of ⁶⁵Zn values elevated following zinc supplementation to nickel-treated rats.     

Blood-brain exchange routes and distribution of65Zn in rat brain

Zinc is essential for normal development and function of the CNS although much is to be learned about brain Zn homeostasis. In these experiments adult male Wistar rats within the weight range 500–600 g were used. Ventriculo-cisternal perfusion was performed to allow the measurement of⁶⁵Zn fluxes between blood and csf across the choroid plexuses. Blood-brain or blood-cerebrospinal fluid barrier permeability to⁶⁵Zn has been determined by graphical analysis in experiments that lasted between 5 and 180 minutes. Cerebral capillary permeability to⁶⁵Zn was found to be low with a K_in of about 5×10^–4ml/min/g. Choroid plexus permeability to⁶⁵Zn was about 12 fold greater, although Zn influx to brain via this route was <5% that across cerebral capillaries. The autoradiographic distribution of⁶⁵Zn in brain showed regional variation with lowest levels in white matter and high levels in the dentate gyrus and hippocampus.     

65Zinc uptake from blood into brain and other tissues in the rat

Zinc is essential for normal growth, development and brain function although little is known about brain zinc homeostasis. Therefore, in this investigation we have studied⁶⁵Zn uptake from blood into brain and other tissues and have measured the blood-brain barrier permeability to⁶⁵Zn in the anaesthetized rat in vivo. Adult male Wistar within the weight range 500–600 g were used.⁶⁵ZnCl₂ and [¹²⁵I]albumin, the latter serving as a vascular marker, were injected in a bolus of normal saline I.V. Sequential arterial blood samples were taken during experiments that lasted between 5 min and 5 hr. At termination, samples from the liver, spleen, pancreas, lung, heart, muscle, kidney, bone, testis, ileum, blood cells, csf, and whole brain were taken and analysed for radio-isotope activity. Data have been analysed by Graphical Analysis which suggests⁶⁵Zn uptake from blood by all tissues sampled was unidirectional during this experimental period except brain, where at circulation times<30 min,⁶⁵Zn fluxes were bidirectional. In addition to the blood space, the brain appears to contain a rapidly exchanging compartment(s) for⁶⁵Zn of about 4 ml/100g which is not csf.     

Possible involvement of plasma histidine in differential brain permeability to zinc and cadmium

Zinc gets into the brain parenchyma across the blood-brain and the blood-cerebrospinal fluid barriers, while cadmium hardly gets into the brain parenchyma. Because histidine may be involved in zinc transport across the brain barrier systems, the binding to histidine was compared between zinc and cadmium to understand the difference in brain permeability to both metals. Sephadex G-10 gel filtration indicated that ¹⁰⁹Cd, unlike ⁶⁵Zn, does not bind to histidine. When the plasma incubated with ⁶⁵Zn or ¹⁰⁹Cd was dialyzed in physiological saline containing histidine (0-10 mM), ⁶⁵Zn concentration in the dialysate was increased with the increase of the histidine concentration, suggesting the transfer of zinc from plasma proteins to histidine. The low affinity of zinc to plasma proteins may be important for brain permeability to this metal. On the other hand, ¹⁰⁹Cd was not detected in the dialysate in the presence of 0.1 mM histidine, which is equal to the concentration in the plasma, suggesting no transfer of cadmium from plasma proteins to histidine. These results suggest that the avid binding of cadmium to plasma proteins is related to brain impermeability to this metal.     

Effects of histidine on tissue zinc distribution in rats

Histidine has been reported to affect body zinc status by increasing urinary zinc excretion. The effects of experimental histidinemia on distribution of⁶⁵Zn in anesthetized rats were studied. Infusion ofl-histidine at a rate sufficient to raise plasma concentrations to approximately 2mm for 6h starting 48 h after a single intraperitoneal⁶⁵Zn injection did not alter⁶⁵Zn activities in a variety of tissues when compared with anesthetized uninfused animals. However, plasma⁶⁵Zn and erythrocyte⁶⁵Zn were decreased, and liver⁶⁵Zn was increased. If⁶⁵Zn was injected intravenously during histidine infusion, net accumulation of zinc by some tissues was increased, but uptake by others was reduced relative to uninfused animals. In all cases, however, uptake expressed relative to plasma⁶⁵Zn levels was increased when allowance was made for the more rapid fall in plasma⁶⁵Zn during histidine infusion. Similar infusions ofd-histidine produced quantitatively similar effects. Since enzymatic mechanisms and amino acid carriers would be expected to show stereoselectivity, such processes are unlikely to be involved in the zinc distribution changes described. The possibility of zinc transport by a hitherto unidentified carrier is discussed. These experiments confirm that histidinemia can affect zinc status, but any associated changes in urinary zinc excretion do not seem adequate to account for the tissue changes found.     

A histidine supplement and regulation of the zinc status in Swiss random mice

The effects of histidine on the zinc status are controversial. In mice, we studied the effects of a moderate histidine supplement on the regulation of the zinc status using subcutaneously administered⁶⁵Zn. In animals fed a zinc-adequate diet, histidine supplement did not cause changes in the zinc status (zinc concentrations,⁶⁵Zn tissue distribution, and tissue specific activities). Neither effects on the regulation of the zinc status (⁶⁵Zn retention, excretion and biological half-life) could be demonstrated. However, the combination of a low zinc diet and moderate histidine supplementation caused changes in the regulation of the zinc status (lower⁶⁵Zn retention, associated with increased fecal excretion and a shorter biological half-life), aggravating the dietary deficiency (lower bone zinc, a shift in the⁶⁵Zn tissue distribution). Reviewing the literature, it seems that only a molar histidine/zinc ration of 2,000 or higher will cause zinc deficiency.     

Polyatomics in zinc isotope ratio analysis of plasma samples by inductively coupled plasma-mass spectrometry and applicability of nonextracted samples for zinc kinetics

Inductively coupled plasma-mass spectrometry (ICP-MS) is a powerful tool for both quantitative multielement analyses of inorganic elements and measurement of isotope ratios (IRs). The main disadvantage of this technique is the existence of polyatomic isobaric interferences at some key masses. Zinc has been investigated for such potential interferences in serum or plasma. The Zn isotopes,⁶⁶Zn and⁶⁸Zn, have no apparent interferences, but³²S¹⁶O₂ and³²S₂ are isobaric with⁶⁴Zn. The possible effects of S and other major components of blood plasma—Na, K, Cl, P, Ca—on Zn IRs were investigated using a series of mineral solutions which simulated human plasma with respect to these elements. The mixture of all mineral elements interfered only with⁶⁴Zn (6.66 ng/mL) and⁷⁰Zn (8.51 ng/mL). Interferences to⁶⁶Zn,⁶⁷Zn, and⁶⁸Zn were minimal containing 0.90, 0.94, and 0.39 ng/mL, respectively. The copresence of Na or S shifted³⁵Cl¹⁶O₂ (atomic mass 67 coming from Cl solution) to³⁵Cl₂ which reduced the contribution to⁶⁷Zn. The hypothesis that Zn IRs obtained from plasma at various intervals after the intravenous administration of enriched⁶⁷Zn to humans would reflect those obtained after extraction of Zn was therefore tested. To compare the two pretreatment methods, “extraction” versus “nonextraction,” specimens were collected from 10 human subjects at intervals of 5 min to 24 h postinjection, and in 4 subjects from 5 min to 9 d postinjection. Two separate aliquots of plasma from each time-point were dried and digested with hydrogen peroxide, and the residue dissolved in nitric acid. One specimen was subjected to zinc extraction using ammonium diethyldithiocarbamate chelate followed by back extraction into nitric acid. The matching aliquot received no further pretreatment. The normalized IRs obtained from⁶⁷Zn/⁶⁶Zn and⁶⁷Zn/⁶⁸Zn in both the “extracted” and “nonextracted” samples agreed well(r ² = 0.976 andr ² = 0.985, respectively) compared to those from other ratios (r ² = 0.838 for⁶⁷Zn/⁶⁴Zn andr ² = 0.747 for⁶⁷Zn/⁷⁰Zn). Considering the minimum possibility of isobaric interferences in plasma samples,⁶⁷Zn/⁶⁸Zn obtained from “nonextracted” samples is sufficient for routine Zn kinetic analysis by ICP-MS.     

Reaction of labelled65ZnCl2,65ZnEDTA and65ZnDTPA with different clay-systems and some alluvial Egyptian soils

Summary The clay fraction separated from an alluvial Egyptian soil and montmorillonite clay mineral were equilibrated with CaCl₂ or NaCl solution then treated with humic acid isolated from composted clover straw to obtain different clay systems: Ca-clay, Ca-clay-HA, Na-clay, Na-clay-HA, Ca-mont and Ca-mont-HA. These clays as well as seven soil samples were reacted with different amounts of labelled⁶⁵ZnCl₂,⁶⁵ZnEDTA and⁶⁵ZnDTPA. The effectiveness of these Zn-sources for maintaining soluble Zn²⁺ ions in the equilibrium solution was the greatest for ZnDTPA and the lowest for ZnCl₂. Ca-clay provided greater Zn sorption capacity than Na-clay, and complexing the clay with humic acid depressed its capacity for Zn sorption. At the pH of the clay-systems (pH=6.5), the possibilities of Zn(OH)₂ formation were reduced especially in the presence of Zn-chelates. Reactions of⁶⁵ZnE DTA and⁶⁵ZnDTPA with the seven soils produced higher levels of soluble Zn²⁺ ions in the equilibrium solution rather than⁶⁵ZnCl₂ meanwhile ZnDTPA was more effective than ZnEDTA. The calculated Zn(OH)₂ ion product in the solution of ZnCl₂-soil systems indicated the precipitation of Zn as Zn(OH)₂. However, this was not valid in the Zn-chelates-soil systems. The results also revealed the role of soil carbonate, organic matter and soil texture as soil variables affecting Zn sorption by natural soils.     

Physiological and morphological traits associated with zinc efficiency in Exacum

Interspecific hybrids of Exacum exhibit variation in the expression of zinc efficiency. This research investigated the genetic basis for this variation and evaluated a series of physiological and morphological traits for their association with zinc efficiency. Chi-square analyses of self-pollinated progeny from both zinc-efficient and zinc-inefficient parents indicate a significant genetic component. One hundred percent of the progeny from the inefficient parent were classified as inefficient, while the progeny from the efficient parent segregated 32% inefficient to 68% efficient. Six plants from each phenotypic class (efficient and inefficient) of the efficient parent were utilized in analyses of plant traits. Statistically significant associations were identified between the zinc-efficient phenotype and mol Zn uptake mg^-1 root, root-to-shoot ratio, specific root length, mol Zn uptake cm^-2 root surface area, and Zn uptake cm^-1 root length. No association was identified between zinc-efficient phenotype and root diameter, transpiration rate, or H⁺ production. Zinc uptake cm^-1 root length had the greatest association with the zinc-efficiency phenotype and was able to discriminate the two phenotypic classes. We suggest that Zn uptake cm^-1 root length is the most significant factor explaining the variation between the zinc-efficient and zinc-inefficient phenotypes in Exacum.     

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 (δ-ALAD) and Na⁺ K⁺ ATPase and uptake of ⁶⁵Zn in blood. The study revealed an increase in the levels of hemoglobin, % hematocrit, activities of δ-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.     

The uptake of zinc by erythrocytes under near-physiological conditions

The in vitro uptake of zinc by erythrocytes was measured under near-physiological conditions, using⁶⁵Zn as a radioactive tracer. Because of the presence of serum albumin—a strong zinc ligand—a low concentration of medium free zinc was maintained. Under these conditions a high-affinity carrier for zinc transport over the cell membrane was identified. With human erythrocytes, a Michaelis constant (K _m ) of 0.2 nM with respect to free medium zinc was measured and aV _max of 4.5 nmoles Zn transported per h/g dry wt. TheK _m for medium Zn increases when the size of the internal erythrocytic Zn pool is augmented, whereasV _max remains virtually unchanged. A model to explain this phenomenon is proposed. It is suggested that this phenomenon could underlie observations, confirmed here, that the in vitro uptake of Zn by animal erythrocytes depends on the Zn status of the animal.     

Development of zinc deficiency in Zn labeled, fully grown rats as a model for adult individuals

The development of zinc deficiency in adults was studied in a metabolism experiment involving 31 adult, female rats labeled homogenously with 65Zn. The animals were fed restricted amounts (8 g/day) of a semisynthetic diet containing either 58 microgram Zn/g (control, n = 7) or 2 microgram Zn/g (Zn deficiency, n = 24). Control animals were sacrificed at day 0 (n = 3) and day 29 (n = 4). Zinc deficient animals were sacrificed at day 1, 2, 4, 7, 11, 16, 22, and 29 (3 animals per group). The development of zinc deficiency comprised 4 phases: (I) Fecal Zn excretion needed several days to adjust to the low level of Zn intake. The high initial Zn loss via feces was counterbalanced mainly by Zn mobilization from the skeleton. (II) During the 2nd week of deficiency Zn mobilization from tissue storage changed transiently to soft tissues (mainly muscle and fat tissue). (III) After the 2nd week the skeleton resumed to mobilize Zn. (IV) At the end of the study the skeleton Zn storage was exhausted and alkaline phosphatase activity indicated severe Zn deficiency. Urinary Zn excretion was too small to contribute quantitatively to changes in Zn metabolism during any phase of Zn deficiency. In conclusion, adults may compensate a deficient Zn supply by mobilizing tissue Zn for several weeks: The skeleton revealed to be the major short-term as well as long-term source of whole body tissue Zn that can be mobilized.     

Measuring Brain Uptake and Incorporation into Brain Phosphatidylinositol of Plasma myo-[2H6]Inositol in Unanesthetized Rats: An Approach to Estimate In vivo Brain Phosphatidylinositol Turnover

The in vivo rate of turnover of phosphatidylinositol (PtdIns) in brain is not known. In brain, certain receptor-mediated signal transduction involves metabolism of PtdIns and a method to measure its turnover in awake animals is useful in studying the effect of lithium and other therapeutic agents. In a method described here, rats were infused subcutaneously with myo-[²H₆]inositol (Ins*) using an osmotic pump and, at 1 and 8 weeks, concentrations of free myo-inositol (Ins) and Ins* in plasma and brain were measured by GC-MS (chemical ionization). Also, PtdIns and PtdIns* together in brain were isolated, and Ins and Ins* from their headgroups were released enzymatically and specific activity of incorporated inositol was measured. The specific activity of inositol reached a steady state in plasma within 1 week of infusion, but not in brain even at 8 weeks. However, in brain, the specific activity of phosphatidylinositol was same as that of inositol at both time-points, suggestive of fast turnover of PtdIns. The animal experiment and the analytical methodology described here should be useful for measuring the rate of turnover of brain PtdIns in pathological and drug treatment conditions.     

The effect of zinc deficiency on the body composition of rats

Body composition and the levels of some plasma metabolites were measured in zinc deficient and control rats with the aim of assessing the nature of the metabolic defects resulting from zinc deficiency. Two experiments, lasting 15 and 20 d, were carried out using 52 immature rats. Zinc deficient animals were fed a diet of 1–2 mg Zn/kg. Pair fed andad libitum control rats received the same diet with 100 ppm zinc added to the drinking water. Feed intake and growth rate were measured, and the carcasses were analyzed for protein, fat, and ash. In each experiment, a group of rats were killed on d 1 to provide pretreatment values and to allow for estimates of net deposition of carcass components. Lactate, urea, and zinc were assayed in plasma, as well as zinc concentration in carcasses and liver. The main effect of zinc deficiency was to reduce feed intake and efficiency of feed conversion, resulting in a reduced proportion of carcass wat because of the reduced feed efficiency, zinc deficiencyper se resulted in an increase in the proportion of fat in the carcass. Plasma lactate concentration was unchanged, but urea concentration increased in both pair fed and zinc deficient rats relative toad libitum fed control animals. The results indicate that a defect in protein synthesis and an increase in energy expenditure, perhaps resulting from increased protein turnover, underlies the reduced growth and efficiency of feed conversion of zinc deficiency.     

Equivalent uptake of organic and inorganic zinc by monkey kidney fibroblasts, human intestinal epithelial cells, or perfused mouse intestine

Zinc (Zn) is recognized as an essential nutrient, and is added as a supplement to animal and human diets. There are claims that zinc methionine (ZnMet) forms a stable complex that is preferentially transported into tissues, and this has contributed to uncertainty about conflicting reports on the bioavailability of various Zn compounds. This study evaluated the cellular and intestinal uptake of inorganic and organic forms of Zn. Steady-state uptake of⁶⁵Zn by human intestine epithelial cells, and monkey kidney fibroblasts was not significantly different with zinc chloride (ZnCl₂), ZnMet, or zinc propionate (ZnProp) (P > 0.05). Uptake of⁶⁵Zn from zinc chelated with EDTA was significantly lower (P < 0.01). In live mice,⁶⁵Zn uptake by perfused intestine and deposition in intestine and liver showed no significant difference between ZnCl₂ and ZnMet. Equimolar [⁶⁵Zn]methionine and zinc[³⁵S]methionine were prepared according to a patented method that yields “ complexed” Zn. Cellular uptake of the radiolabeled methionine was <0.1% of the radiolabeled Zn from these complexes, indicating separate uptake of the Zn and methionine. Gel filtration did not distinguish between⁶⁵Zn in ZnCl₂, ZnProp, or reagent ZnMet, though feed-grade ZnMet containing >10% protein did give a higher-mol-wt form of⁶⁵Zn. Results of this study show equivalent uptake of Zn from inorganic and organic compounds, and support recent feed trials on Zn bioavailability.     

Postnatal accumulation of zinc by the rat hippocampus

Timm's staining material has been detected in the rat hippocampus as early as day 1 postnatally. However, staining was diffuse and widespread and light granulation was observed only in the mossy fiber layer. By day 6 postnatally most diffuse staining had disappeared and the characteristic pattern of granulation had intensified in the mossy fiber layer. Pronounced staining of the mossy fibers became apparent from day 6. Electron microscopic autoradiography indicated that⁶⁵Zn injected intraperitoneally into suckling pups became localized largely in the axons and axon terminals of the mossy fiber layer in the CA3 and CA4 regions of the Horn of Ammon. In vitro studies with hippocampal slices have demonstrated that zinc is accumulated by an active transport system, but the kinetic characteristics of this uptake do not appear to alter with age. Zinc located intracellularly in the hippocampus appears to be associated mainly with large molecular weight ligands, with more than 75% of newly acquired zinc being bound to substances having molecular weights greater than 70,000 Daltons.     

Uptake of radiolabeled copper from portal blood containing fructose or glucose

The present investigation was designed to study the uptake of⁶⁷Cu when administered directly, into the portal vein, along with either functose or glucose, by the liver and extrahepatic tissues. Following weaning, male Sprague-Dawley rats were fed for 3 wk either commercial laboratory ration (chow) or semipurified diets deficient in Cu (0.6 ppm) or supplemented with Cu (6.0 ppm) and containing 62% carbohydrate as either fructuse or cornstarch. After an overnight fast, a single dose of rat plasma (0.1 mL) containing fructose or glucose extrinsically labeled with⁶⁷Cu was injected directly into their portal vein. Although not always statistically significant, rats fed chow retained more radioactivity in the liver and several extrahepatic tissues when⁶⁷Cu was administered with fructose than with glucose. Regardless of Cu status, rats fed diets containing fructose retained more radioactivity in extrahepatic tissues than rats fed starch. There was an increased uptake of⁶⁷Cu by the liver, blood, muscle, and fat pad when fructose as compared to glucose was injected in combination with the isotope. These data strongly suggest that Cu requirements or utilization are greater when fructose is the main dietary carbohydrate. The results may also in part explain the reason for the increased severity of Cu deficiency in rats fed fructose.     

Normolipidemic Effect of Antioxidants in Low Cholesterol-Modified Poultry Egg<Superscript>Ψ</Superscript> on Zn-induced Dyslipidemia and Liver Pathology in Wistar Rats

A low cholesterol (CH)-modified poultry egg (ME^Ψ) containing more vitamin E, lenolenic acid, and minerals Cu and Mg but low total lipid (TL) and Zn contents than the conventional egg evaluated to reduce the severity of dyslipidemia induced by excessive Zn in the diet. The experimental data was recorded on male rats fed on normolipidemic (NL) semi-synthetic basal diet containing 20 mg Zn/kg diet in control group I, Zn supplemented dyslipidemic diet-A (Zn-DL-A) and B (Zn-DL-B) containing 40 and 80 mg Zn/kg diet in groups II and III, and ME^Ψ-mixed Test diet-A (Zn-DL-A + 4 ME^Ψ) and Test diet-B (Zn-DL-B + 4 ME^Ψ) in groups IIEM and IIIEM, respectively, for 180 and 90 days. Data recorded on liver and blood lipid profiles showed reduction in the concentration of TL, CH, triglycerides, and glycogen (GG) in liver consequently leading to their rise in blood serum including rise in VLDL-c and LDL-c but fall in HDL-c in groups II and III rats that reversed after ME^Ψ treatment resulting in rise of their levels in the liver and fall in the blood of groups IIEM and IIIEM rats, respectively. Mineral status in the liver showed a rise in Zn but fall in Cu and Mg levels in groups II and III that was reversed after ME^Ψ treatment resulting in fall in Zn and rise in Cu and Mg concentration in the liver of groups IIEM and IIIEM rats. Hepatopathogical studies showed reduction in the dilatation of long citernal profile of endoplasmic reticulum and increase in GG and TL granules in the cytoplasm of hepatocytes of groups IIEM and IIIEM after ME^Ψ treatment than those of groups II and III rats. It was concluded that the inclusion of ME^Ψ would be helpful in reducing dyslipidemia by correcting the ionic imbalance generated by excessive Zn intake in rats or by drugs, even in chronic diseased conditions without aggravating risk factors for heart diseases in humans that need further studies.