Effect Of Dietary Zinc Deficiency Research Articles

Effect of dietary zinc deficiency on acetylcholinesterase activity in the male Wistar rat brain subregions

Effect of dietary zinc deficiency on acetylcholinesterase activity in the male Wistar rat brain subregions

Effects of Dietary Zinc Deficiency on Skin Breaking Strength and Fatty Acid Composition in Broiler Chickens and Pekin Ducks.

This study is aimed at investigating the effect of dietary zinc deficiency (ZnD) on skin breaking strength and skin chemical and fatty acid composition in broiler chickens and Pekin ducks. A total of 200 1-day-old male broiler chickens and 200 1-day-old male ducklings were used in a 2 × 2 factorial design and randomly allocated to 4 treatments with 10 replicated cages of 10 birds per cage. Diets containing zinc at 84.77mg/kg and 20.42mg/kg were regarded as the control diet and zinc-deficient diet, respectively. The results showed the following: (1) dietary ZnD decreased (P < 0.05) the breast skin weight (day 21), breast skin index (day 21), skin fat content (day 7), and skin Zn content (days 7, 14, and 21) of ducks, but only increased (P < 0.05) the skin fat content of broiler chickens at 7days of age; ducks had a higher (P < 0.05) breast skin weight, breast skin index, and skin breaking strength as well as a lower skin fat content (days 7 and 14) than those in broiler chickens. (2) Dietary ZnD decreased the content of myristic acid (day 21) and increased the content of oleic acid (day 7) content in the skin of ducks and increased the palmitic acid (day 7) content in the skin of broiler chickens (P < 0.05) and increased the MUFA (day 7) content in the skin and the atherogenic index (day 21) in ducks. The contents of myristic acid (day 21), stearic acid (day 21), and oleic acid (days 7, 14, and 21) in the skin of broiler chickens were lower (P < 0.05) than those in ducks of the same age. In conclusion, using skin weight, skin index and skin MUFA content as criteria, the results indicated that meat ducks were more sensitive to dietary ZnD than broiler chickens. Using skin fat content as criterion, the results indicated that broiler chickens were more sensitive to dietary ZnD than meat ducks.

Effects of dietary zinc deficiency on esophageal squamous cell proliferation and the mechanisms involved.

BACKGROUNDDietary zinc deficiency has been shown to be associated with the development of esophageal cancer in humans, but the exact mechanism of action is not knownAIMTo observe the effects of dietary zinc deficiency on esophageal squamous cell proliferation. METHODSThirty C57BL/6 mice were randomly divided into three groups: A zinc-sufficient (ZS) group, zinc-deficient (ZD) group, and zinc-replenished (ZR) group. For weeks 1–10, zinc levels in the mice diets were 30.66–30.89 mg/kg in the ZS group and 0.66–0.89 mg/kg in the ZD and ZR groups. During weeks 10–12, the ZR group was switched to the ZS diet; the other two groups had no changes in their diets. Changes in body weight, serum, and esophageal tissue zinc concentrations were assessed as well as differences in the expression of proliferating cell nuclear antigen (PCNA), mitogen-activated protein kinase p38 (p38MAPK), nuclear factor kappa B (NF-κB) p105, NF-κB p65, and cyclooxygenase (COX)-2 proteins in the esophageal mucosa.RESULTSThe body weight and zinc concentration in the serum and esophageal mucosa were significantly lower in the ZD and ZR groups than in the ZS group (P < 0.05). In ZD mice, there was a marked proliferation of basal cells in the esophageal mucosa, resulting in a disturbance in the arrangement of basal cells in layers 2–4, a thickening of the squamous layer, and a significant increase in the expression of the above-mentioned five proteins involved in proliferation and inflammation in the esophageal mucosa. Two weeks after switching to the ZS diet, the serum zinc concentration in the ZR group increased, and the expression of PCNA, NF-κB p105, and COX-2 decreased, but the concentration of zinc in the esophageal mucosa and the structure of the esophageal mucosa did not display any significant changesCONCLUSIONThe ZD diet decreased the growth rate and promoted the proliferation of esophageal squamous cells in mice. The mechanism of proliferation was related to the induced overexpression of COX-2, P38, PCNA, and NF-κB (p105 and p65), and the ZR diet reduced the expression of PCNA, NF-κB p105, and COX-2, thereby reversing this process.​

The Role of Zinc Status on Spatial Memory, Hippocampal Synaptic Plasticity, and Insulin Signaling in icv-STZ-Induced Sporadic Alzheimer's-Like Disease in Rats.

Alzheimer's disease (AD), especially its sporadic form (sAD), is of multifactorial nature. Brain insulin resistance and disrupted zinc homeostasis are two key aspects of AD that remain to be elucidated. Here, we investigated the effects of dietary zinc deficiency and supplementation on memory, hippocampal synaptic plasticity, and insulin signaling in intracerebroventricular streptozotocin (icv-STZ)-induced sAD in rats. The memory performance was evaluated by Morris water maze. The expression of hippocampal protein and mRNA levels of targets related to synaptic plasticity and insulin pathway was assessed by Western blot and real-time quantitative PCR. We found memory deficits in icv-STZ rats, which were fully recovered by zinc supplementation. Western blot analysis revealed that icv-STZ treatment significantly reduced hippocampal PSD95 and p-GSK3β, and zinc supplementation restored the normal protein levels. mRNA levels of BDNF, PSD95, SIRT1, GLUT4, insulin receptor, and ZnT3 were found to be reduced by icv-STZ and reestablished by zinc supplementation. Our data suggest that zinc supplementation improves cognitive deficits and rescues the decline in key molecular targets of synaptic plasticity and insulin signaling in hippocampus caused by icv-STZ induced sAD in rats.

Effect of Dietary Zinc Deficiency on Proliferation of Esophageal Squamous Cells in Mice and Related Mechanism

Effect of Dietary Zinc Deficiency on Proliferation of Esophageal Squamous Cells in Mice and Related Mechanism

Morphological changes in spleen after dietary zinc deficiency and supplementation in Wistar rats.

Study was conducted to determine the effect of dietary zinc deficiency and supplementation on the spleen morphology. Pre-pubertal Wistar rats (40-50 g) were divided into two groups with 6 sub-groups each viz. zinc control (ZC, 100 μg/g zinc diet), pair fed (PF, 100 μg/g zinc diet), zinc deficient (ZD, <1 μg/g zinc diet, zinc supplementation control (ZCS), zinc supplementation pair-fed (PFS) and zinc supplementation deficient (ZDS, 100 μg/g zinc control diet). Experiments were set for 2- and 4-weeks followed by 4 weeks of zinc supplementation. In the present study body weight and BMI decreased significantly along with incidence of splenomegaly as typified by the increased splenic index in deficient groups compared with that of respective control groups. Histopathological changes such as disorganization of red pulp, several infiltered lymphocytes, vacuolization, loss of cellularity, karyolysis, dissolution of matrix, indistinct differentiation between red and white pulp were evident in spleen of 2ZD and 4ZD group animals. Degeneration was more severe after 4 weeks of zinc deficiency as giant cells formation and hypertrophy were also evident. The findings revealed that zinc deficiency causes growth retardation and splenomegaly. Degenerative and atrophic changes in rat spleen suggest reduced cellular defense potential which will have a direct effect on immunity. Zinc supplementation may prove to be beneficial as there were varying degrees of cellular recovery after cessation of zinc deficiency.

Dietary zinc deficiency induces oxidative stress and promotes tumor necrosis factor-α- and interleukin-1β-induced RANKL expression in rat bone.

We investigated the effects of dietary zinc deficiency on oxidative stress and bone metabolism. Four-week-old male Wistar rats were randomly assigned to one of three groups for 4 weeks: a zinc-adequate group (30 ppm); a zinc-deficient group (1 ppm); and a pair-fed group (30 ppm) that was pair-fed to the zinc-deficient group. The iron content and the thiobarbituric acid reactive substance level in bone were higher in the zinc-deficient group than in the zinc-adequate and pair-fed groups. The mRNA expression level of osteoblastogenesis-related genes such as bone morphogenetic protein 2 and runt-related transcription factor 2 was lower in the zinc-deficient group than in the zinc-adequate and pair-fed groups. In contrast, the mRNA expression levels of tumor necrosis factor-α, interleukin-1β and osteoclastogenesis-related genes such as receptor activator of nuclear factor-κB ligand and nuclear factor of activated T cells cytoplasmic 1 were higher in the zinc-deficient group than in the zinc-adequate and pair-fed groups.These findings suggested that dietary zinc deficiency reduced osteoblastogenesis via a decrease in the expression of bone morphogenetic protein 2 and increased osteoclastogenesis via enhancement of the expression of receptor for activator of nuclear factor-κB ligand induced by oxidative stress-stimulated tumor necrosis factor-α and interleukin-1β.

Dietary zinc deficiency effects dorso-lateral and ventral prostate of Wistar rats: histological, biochemical and trace element study.

Zinc deficiency has become a global problem affecting the developed and developing countries due to inhibitors in the diet which prevents its absorption or due to a very low concentration of bioavailable zinc in the diet. Being present in high concentration in the prostate and having diverse biological function, we investigated the effects of dietary zinc deficiency for 2 and 4 weeks on dorso-lateral and ventral prostate. Sixty prepubertal rats were divided into three groups: zinc control (ZC), pair fed (PF) and zinc deficient (ZD) and fed on 100 μg/g (zinc control and pair fed groups) and 1 μg/g (zinc deficient) diet. Zinc deficiency was associated with degenerative changes in dorso-lateral and ventral prostate as made evident by karyolysis, karyorhexis, cytoplasmolysis, loss of cellularisation, decreased intraluminar secretion and degeneration of fibromuscular stroma. In response, protein carbonyl, nitric oxide, acid phosphatase, 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase increased, exhibiting variable level of significance. Total protein and total zinc concentration in dorso-lateral and ventral prostate as well as in serum decreased (P < 0.001). Decrease (P < 0.001) was recorded in serum FSH and testosterone after 2 and 4 weeks of zinc deficiency. The changes were more prominent after 4 weeks of synthetic zinc deficient diet. The results indicate that zinc deficiency during prepubertal period affects the prostate structure, total protein concentration, enhanced protein carbonyl concentration, nitric oxide as well as acid phosphatase activities and impaired hydroxysteroid dehydrogenase activities. Evidently these changes could be attributed to dysfunction of dorso-lateral and ventral prostate after dietary zinc deficiency as well as impairment of metabolic and secretory activity, reduced gonadotropin levels by hypothalamus -hypophysial system which is indicative of a critical role of zinc in maintaining the prostate integrity.

Effect of dietary zinc deficiency on ischemic vulnerability of the brain

Deficiency of zinc, which modulates glutamate release, might increase ischemic vulnerability of the brain. We examined effects of dietary zinc deficiency for 2 weeks on ischemic vulnerability in several brain regions using dynamic positron autoradiography technique and [18F]2-fluoro-2-deoxy-d-glucose with rat brain slices. In the normal diet group, the cerebral glucose metabolic rate (CMRglc) was not significantly different from that of the ischemia-unloaded control even after the loading of ischemia for 45min. However, in the zinc-deficient diet group, CMRglc was significantly lower than that of the ischemia-unloaded control after loading of ischemia for 45min. With treatment of MK-801 (NMDA receptor antagonist) from the start of ischemia loading, CMRglc was not significantly different from that of the ischemia-unloaded control. These findings, obtained for all analyzed brain regions, suggest that dietary zinc deficiency increased ischemic vulnerability in the brain, and that glutamate might contribute to this effect through activation of the NMDA receptor.

Effects of Cigarette Smoke and Ethanol Intake on Mouse Oesophageal Mucosa Changes Induced by Dietary Zinc Deficiency and Deoxycholic Acid Supplementation

The noxious effects of dietary zinc deficiency (ZD) and deoxycholic bile acid (DCA) supplementation in the oesophagus were investigated. The additional influence of cigarette smoke and ethanol intake on the changes in the oesophageal mucosa induced by dietary ZD plus DCA was also assessed. Male C57BL/6 mice were allocated into four groups: Group 1 was fed control diet and groups 2-4 were fed ZD plus DCA diet. After 5 weeks, groups 3 and 4 were exposed to 10% ethanol intake or cigarette smoke for 15 weeks, respectively. All animals were euthanized at the end of week 20, and the oesophagus, lung, liver and colon were collected and analysed by conventional morphology. Cell proliferation was assessed in the oesophageal mucosa by Ki-67 immunohistochemistry and cyclooxygenase 2 (COX-2) protein by Western blotting. Dietary ZD plus DCA treatment induced mild hyperkeratosis and hyperplasia, increased cell proliferation index and COX-2 protein expression in the oesophagus, and intranuclear inclusion, karyocytomegaly and microvesicular fatty change in the liver. Cigarette smoke increased COX-2 protein expression in oesophageal mucosa and irregular enlargement of alveolus and alveolar ductal air spaces, while ethanol enhanced liver damage induced by ZD plus DCA diet. These findings indicate that dietary ZD plus DCA treatment during 20 weeks induces a pattern of chemical oesophageal injury but not Barrett's-like lesions.

Effect of dietary zinc deficiency on testes of Wistar rats: Morphometric and cell quantification studies

The present study investigates the effect of dietary zinc deficiency on testes of Wistar rats. Pre-pubertal rats (40–50 g) were divided into three groups of 10 each viz. zinc control (ZC) and pair fed (PF) [100 ppm zinc diet] and zinc deficient (ZD) [1 ppm zinc diet]. Experiments were set for 2- and 4-weeks. Pre-pubertal rats fed zinc deficient diet for 2- and 4-weeks exhibited significant ( P < 0.05) decrease in diet consumption when compared with their respective control groups. Parallel to the reduced diet consumption, a significant ( P < 0.05) decrease in body and testicular weight of ZD animals was also observed. These observations indicate that the zinc deficiency reduces diet consumption and growth of the animals. Histological studies revealed degeneration in testes of ZD rats as evident by decreased seminiferous tubular diameter and Leydig cell nuclear diameter. Decreased Leydig cell nuclear diameter is responsible for disruption of the biochemical function of Leydig cell. Testicular atrophy (viz. wavy tunica propria, karyolysis, pyknosis, karyorhexis, apoptotic bodies, multinucleated giant cells, few sperms in the lumen, atrophied Leydig cells and accumulation of oedematous fluid in the interstitium) accompanied by significant loss of germ/somatic cells (viz. Type A and Type B spermatogonia, leptotene, zygotene, pachytene spermatocytes, Golgi, cap and acrosome spermatids, Sertoli and Leydig cell) was evident in ZD groups. The degeneration was severe after 4-weeks of zinc deficiency. These observations provide evidence that the functional and morphological changes in testes are probably due to zinc deficiency. Further, the increased oedematous fluid in the interstitial region is due to the cellular death. Impairment of spermatogenesis can be attributed to the direct action of zinc on testes or indirectly from Leydig cell degeneration indicating that zinc is a critical component for maintenance of both mitotic and meiotic stages of spermatogenesis.

Renal metallothionein responds rapidly and site specifically to zinc repletion in growing rats

Metallothionein (MT) is important for heavy metals and free radical protection in the kidney. MT is responsive to zinc and primarily localized within the renal cortex. However, site-specific renal responses to dietary zinc repletion are understudied. The objective of this study was to examine the effects of dietary zinc deficiency and repletion on renal MT concentration and immunolocalization in rats. Weanling male Sprague Dawley rats were randomly assigned to either a zinc-deficient, zinc control, or pair-fed to zinc-deficient group. Half of the zinc-deficient and pair-fed rats were repleted with the control diet ad libitum for an additional 24h. Renal tissue samples were assessed for total zinc, MT concentrations and MT immunostaining. Dietary zinc deficiency reduced renal zinc and MT concentrations, and attenuated intensity and localization of MT. Dietary zinc repletion for 24h restored renal zinc and MT concentrations, the latter primarily in the proximal convoluted tubules of the cortex. Concentrations of renal MT, but not zinc, were elevated by diet restriction and MT (microg/mg protein) and partially normalized by 24h diet repletion. In conclusion, renal MT modification due to zinc deficiency or diet restriction can be rapidly normalized in a site-specific manner with normal dietary zinc intake. The results support a role for MT in kidney homeostasis, in particular at the level of the proximal tubules in the cortex. The speed of MT repletion may have clinical implications for dietary zinc in the treatment of acute and chronic renal pathology due to toxins and free radicals.

Zinc-deficient rats have more limited bone recovery during repletion than diet-restricted rats.

The objective of this study was to investigate the effects of dietary zinc deficiency and diet restriction on bone development in growing rats, and to determine whether any adverse effects could be reversed by dietary repletion. Weanling rats were fed either a zinc-deficient diet ad libitum (ZD; <1 mg zinc/kg) or nutritionally complete diet (30 mg zinc/kg) either ad libitum (CTL) or pair-fed to the intake of the ZD group (DR; diet-restricted) for 3 weeks (deficiency phase) and then all groups were fed the zinc-adequate diet ad libitum for 3, 7, or 23 days (repletion phase). Excised femurs were analyzed for bone mineral density (BMD) using dual-energy x-ray absorptiometry, and plasma was analyzed for markers of bone formation (osteocalcin) and resorption (Ratlaps). After the deficiency phase, ZD had lower body weight and reduced femur BMD, zinc, and phosphorus concentrations compared with DR; and these parameters were lower in DR compared with CTL. Femur calcium concentrations were unchanged among the groups. Reduced plasma osteocalcin in ZD and elevated plasma Ratlaps in DR suggested that zinc deficiency limits bone formation while diet restriction accelerates bone resorption activity. After 23 days of repletion, femur size, BMD, and zinc concentrations remained lower in ZD compared with DR and CTL. Body weight and femur phosphorus concentrations remained lower in both ZD and DR compared with CTL after repletion. There were no differences in plasma osteocalcin concentrations after the repletion phase, but the plasma Ratlaps concentrations remained elevated in DR compared with CTL. In summary, both ZD and DR lead to osteopenia during rapid growth, but the mechanisms appear to be due to reduced modeling in ZD and higher turnover in DR. Zinc deficiency was associated with a greater impairment in bone development than diet restriction, and both deficiencies limited bone recovery during repletion in growing rats.

Expression of P2X6, a purinergic receptor subunit, is affected by dietary zinc deficiency in rat hippocampus.

The purpose of these experiments was to determine whether dietary zinc depletion affected protein expression in the hippocampus. Eleven weanling Sprague-Dawley male rats (21 d) were fed the AIN-93G diet containing 1.5 ppm zinc and supplemented with 30 ppm of zinc in the drinking water. After 1 wk, the rats were randomly divided into three groups: control (n=3), pair fed (n=3), and zinc restricted (n=5). All groups consumed the same diet. The zinc-restricted group consumed water containing no zinc. The rats were sacrificed 3 wk later. Chelatable zinc levels in the hippocampus, as measured by N-(6-methoxy-8-quinolyl)-para-toluenesulfonamide (TSQ) staining, were significantly reduced in the zinc-restricted group. Analysis of hippocampal protein expression by two-dimensional electrophoresis (2DE) revealed increased expression of the P2X6 purinergic receptor in the zinc-restricted rats, as determined by MALDI mass spectrometry (MS) and database analysis. The data provided evidence for the dual effects of dietary zinc deficiency on the hippocampus, reducing ionic zinc levels and stimulating protein expression. The role the P2X6 receptor plays in the physiological response of the hippocampus to zinc depletion remains to be determined.

Dietary Zinc Deficiency and Protein-Energy Malnutrition Decrease in Vitro Murine T Lymphocyte Cell Cycle Progression

Abstract The objective of this study was to investigate the effects of dietary zinc deficiency and protein-energy malnutrition (PEM), alone and in combination, on murine splenic T-lymphocyte subpopulations and cell cycle progression using flow cytometry. Four month old C56BL/6 female mice were fed Zn-deficient (ZnDF), low protein (LP), combined Zn-deficient and low protein (ZnDF&LP), energy-restricted (ER) or control (CTRL) diet for 4 weeks. The CD4+/CD8+ ratio of T lymphocytes was not altered by the deficient diets, however, the total percentage of CD4+ plus CD8+ cells within the CD3+ population was less in all deficient groups compared to the CTRL group. When spleen cells were stimulated with concanavalin A (ConA) in the presence of 2-mercaptoethanol, the ZnDF&LP, ZnDF and LP groups had significantly fewer cells in both early and late S phase and significantly more cells in the G0 or resting state than the CTRL group. The ER group had significantly fewer cells in total S phase than the CTRL group. These...

Influence of dietary zinc deficiency during development on hepatic CYP2C11, CYP2C12, CYP3A2, CYP3A9, and CYP3A18 expression in postpubertal male rats

The present study investigated the effect of dietary zinc deficiency during the developmental period on hepatic cytochrome P450 (CYP) expression in postpubertal male rats. Twenty-one-day-old weanling male Wistar rats were randomly assigned to one of the following dietary groups: zinc-adequate (31 mg zinc/kg diet); marginal zinc-deficient (3 mg zinc/kg diet); severe zinc-deficient (1 mg zinc/kg diet); or pair-fed control for either the marginal or severe zinc-deficient group. All rats were killed at 63 days of age. Compared with the corresponding pair-fed controls, marginal zinc deficiency decreased CYP2C11-mediated testosterone 2α- and 16α-hydroxylase activities by 43 and 42%, respectively, whereas severe zinc deficiency reduced each of these activities by approximately 60%. The decrease in CYP2C11 activity was accompanied by a reduction in CYP2C11 protein and mRNA levels, as assessed by immunoblot and reverse transcription-polymerase chain reaction (RT-PCR) assays, respectively. Additional RT-PCR analysis indicated that severe zinc deficiency decreased CYP3A2 and CYP3A18 mRNA levels by 49 and 43%, respectively, whereas it increased CYP2C12 (253%) and CYP3A9 (238%) mRNA expression. Plasma testosterone concentration was decreased by 67% in the marginal zinc-deficient group when compared with the corresponding pair-fed control group. By comparison, it was below the limit of quantification (0.2 ng/mL) in the severe zinc-deficient rats. Overall, these results indicate that dietary zinc deficiency during the developmental period feminized the hepatic gene expression of the sexually dimorphic CYP2C11, CYP3A2, CYP3A18, CYP2C12, and CYP3A9 in postpubertal male rats.

Effect of dietary zinc deficiency on hematological and biochemical parameters and concentrations of zinc, copper, and iron in growing rats

Zinc has a wide spectrum of biological activities and its deficiency has been related to various dysfunctions and alterations of normal cell metabolism. The effects of adequate Zn level (38 mg/kg diet, control) and two low levels that create Zn deficiencies (19 mg/kg diet, 1/2 of control and 3.8 mg/kg diet, 1/10 of control) were investigated in growing male and female rats for 10 weeks. This allowed for evaluation of the effects these Zn levels may have on body weight gain, specific organ weights, blood parameters, and serum concentrations of Zn, Cu and Fe. Rats fed Zn-deficient diets gained less ( P<0.05) than the control groups. There was increase ( P<0.05) in liver and spleen weights, and a decrease ( P<0.05) in testes weight. However, brain, kidney, heart, and lung weights were not affected ( P<0.05). Hematological parameters that were decreased ( P<0.05) by Zn deficiency included hemoglobin (Hb), total erythrocyte count (TEC) and packed cell volume (PCV) with the magnitude being dose-dependent. Serum concentrations of total protein, globulin, glucose, and high density lipoprotein (HDL) also decreased ( P<0.05) in a dose-dependent manner. Zn deficiency increased ( P<0.05) total leukocyte count (TLC) and concentrations of serum albumin, total lipids, cholesterol, triglycerides and low density lipoprotein (LDL) in a dose-dependent manner. Serum concentrations of urea and creatinine were, however, not affected ( P<0.05) by zinc deficiency. Zn-deficient rats had lower serum concentrations of Zn, Cu and Fe. These results showed that Zn deficiency has negative effects on growth rate, specific organ weights, hematological parameters, and serum levels of Zn, Cu and Fe, especially in rats fed the lowest Zn level.

Reduced Growth and Skeletal Changes in Zinc-Deficient Growing Rats Are Due to Impaired Growth Plate Activity and Inanition

We investigated the effects of dietary zinc deficiency on skeletal metabolism in an animal model. Thirty 21-d-old male Sprague-Dawley rats were fed for 28 d either a zinc-deficient (ZD) diet (1 mg zinc/kg) or a normal diet ad libitum (AL, 50 mg zinc/kg) or in the same quantity as the ZD (pair-fed, PF). Only in the ZD group were general physical signs of zinc deficiency observed. Compared with the AL and PF rats, ZD rats showed significantly lower mean values in ponderal growth rate, femur weight and length, circulating levels of insulin-like growth factor-I, bone mechanical properties and concentration of zinc and, on histomorphometry, a decrease in the thicknesses of the overall growth plate and hypertrophic cartilage. In contrast, although bone volume was significantly lower in the ZD and PF rats than in the AL rats, no difference was observed between the ZD and PF rats. Osteoclast surface/bone surface and osteoclast number/bone surface ratios were significantly greater in PF rats than in the other two groups and not different in ZD and AL rats. Collectively, these data indicate that zinc deficiency has profound effects on the skeletal system of growing rats. In particular, the effects of zinc deficiency on bone growth and mass are the result of the reduced activity of the growth plate, likely mediated by impairment in the insulin-like growth factor-I system. We did not demonstrate an effect on bone mass via increased bone resorption.

Effects of dietary zinc deficiency on homocysteine and folate metabolism in rats

In rats, zinc deficiency has been reported to result in elevated hepatic methionine synthase activity and alterations in folate metabolism. We investigated the effect of zinc deficiency on plasma homocysteine concentrations and the distribution of hepatic folates. Weanling male rats were fed ad libitum a zinc-sufficient control diet (382.0 nmol zinc/g diet), a low-zinc diet (7.5 nmol zinc/g diet), or a control diet pair-fed to the intake of the zinc-deficient rats. After 6 weeks, the body weights of the zinc-deficient and pair-fed control groups were lower than those of controls, and plasma zinc concentrations were lowest in the zinc-deficient group. Plasma homocysteine concentrations in the zinc-deficient group (2.3 ± 0.2 μmol/L) were significantly lower than those in the ad libitum-fed and pair-fed control groups (6.7 ± 0.5 and 3.2 ± 0.4 μmol/L, respectively). Hepatic methionine synthase activity in the zinc-deficient group was higher than in the other two groups. Low mean percentage of 5-methyltetrahydrofolate in total hepatic folates and low plasma folate concentration were observed in the zinc-deficient group compared with the ad libitum-fed and pair-fed control groups. The reduced plasma homocysteine and folate concentrations and reduced percentage of hepatic 5-methyltetrahydrofolate are probably secondary to the increased activity of hepatic methionine synthase in zinc deficiency.

Effect of dietary zinc deficiency on brain metallothionein-I and -III mRNA levels during stress and inflammation

Zinc is an essential heavy metal for the normal function of the central nervous system (CNS), but the knowledge of its metabolism and functions is scarce. In this report we have studied the effect of a zinc deficient diet on the regulation of brain metallothioneins (MTs). In situ hybridization analysis revealed that brain MT-I induction by restraint stress was significantly blunted in some but not all brain areas in the mice fed the zinc deficient diet compared to normally fed mice. In contrast, brain MT-I induction by the administration of bacterial lipopolysaccharide (LPS) was not significantly lower in the mice fed the zinc deficient diet. In contrast to MT-I, MT-III mRNA levels were minimally affected by either stress or LPS. Yet, significant decreasing effects of the zinc deficient diet were observed in areas such as the neocortex, CA1–CA3 neuronal layer and dentate gyrus of the hippocampus, and the Purkinje neuronal layer of the cerebellum. These results demonstrate that dietary zinc deficiency impairs the response of brain MTs during both stress and LPS-elicited inflammatory response in a highly specific manner.