Oral Zinc Administration Research Articles

Effect of Zinc Supplementation on Duration of Acute Watery Diarrhoea in Children aged Six Months to Five Years

Background: Diarrheal disease is one of the leading causes of morbidity and mortality among young children under five years of age in developing countries. The longer duration of diarrhea increases the chance of morbidity and mortality. Zinc supplementation decreases the duration of diarrhea. It is a straightforward, acceptable, low-cost, and effective treatment that could easily be affordable in our country.
 Objective: This study aimed to determine the effect of zinc supplementation on the duration of acute watery diarrhea. Materials and Methods: A total of 106 subjects were included in this study over six months, from December 2014 to May 2015. Detailed information was obtained from each patient. A total of 106 patients were taken. Among them, 53 patients (group A) were given zinc with Oral Rehydration Salts (ORS), and 53 patients (Group B) were given ORS only. However, three patients in each group were lost during follow-up. Data were analyzed by using a standard statistical method (SPSS version 16.0).
 Results: The duration of diarrhea was three days in 56% of patients in the zinc-supplemented group, but it was only 20% in the control group. The frequency of stool gradually decreased over five days. It was more marked in zinc supplemented group. The p-value was 0.001. Vomiting occurred in 30% of patients in zinc supplemented group, and in the control group, it was only 20%. The p-value was 0.5. So we conclude that oral zinc administration in acute watery diarrhea (AWD) decreases the duration and causes early recovery and may be considered in the management of AWD.
 Conclusion: Oral zinc administration in acute watery diarrhea decreases the duration and frequency of diarrhea in children aged six months to five years by changing the natural course of acute diarrheal disease.
 TAJ 2022; 36: No-1: 107-112

Effects of Daily Zinc Alone or in Combination with Other Nutrient Supplements on the Risk of Malaria Parasitaemia: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Zinc supplementation has been explored as a potential intervention to reduce the risk of malaria parasitaemia in randomised controlled trials (RCTs). However, inconsistent evidence has been obtained regarding the efficacy of zinc supplementation in the context of malaria prevention. This systematic review was implemented to survey the existing literature to determine the effects of the daily oral administration of zinc, either alone or in combination with other nutrient supplements, on the risk of malaria parasitaemia. The systematic review was prospectively registered in the PROSPERO database CRD42023424345 and followed PRISMA protocols. A comprehensive search was conducted across multiple databases, including Embase, MEDLINE, Ovid, PubMed, Scopus, ProQuest, and Google Scholar, from their inception until 6 May 2023. The risk of bias in RCTs was assessed using the Cochrane Risk of Bias Tool 2 (RoB 2). The effect sizes, represented as risk ratios (RRs) with 95% confidence intervals (CIs), were standardised by transforming them into log RRs and then pooling them using a fixed-effects or random-effects model depending on the heterogeneity across studies. Comparisons were made between individuals who received zinc alone or zinc in combination with other micronutrient supplements and those who did not receive zinc. A total of 1339 articles were identified through the database searches, and after the screening and selection process, 10 studies were included in the final synthesis. The meta-analysis revealed that zinc supplementation alone did not significantly affect the risk of malaria parasitaemia compared with placebo (p = 0.30, log RR = 0.05, 95% CI: -0.05-0.15, I2 = 0.00%, with 566 malaria cases in the zinc intake group and 521 malaria cases in the placebo group). However, the analysis demonstrated a borderline significant effect of zinc supplementation in combination with other micronutrients on the risk of malaria parasitaemia compared with placebo (p = 0.05, log RR = 1.31, 95% CI: 0.03-2.59, I2 = 99.22%, with 8904 malaria cases in the zinc intake group and 522 malaria cases in the placebo group). The findings of this systematic review indicate that zinc supplementation, either alone or combined with the supplementation of other micronutrients such as vitamin A, iron, or multiple nutrients, does not significantly alter the risk of malaria parasitaemia. Further research with larger sample sizes is warranted to explore the potential effects of multi-nutrient supplementation and to identify more specific micronutrients and additional factors associated with the risk of malaria, rather than just zinc alone, among individuals in different malaria-endemic areas.

Short-term zinc supplementation of zinc-deficient seniors counteracts CREMα - mediated IL-2 suppression

BackgroundAging is accompanied by a dramatic decline in the interleukin (IL)-2 production capacity of human immune cells, thus making seniors more susceptible to a variety of age-related diseases. A common cause of impaired cytokine production in advanced age is a deficiency of the essential micronutrient zinc. Nevertheless, the molecular mechanisms underlying a zinc deficiency-induced decrease in IL-2 production have not yet been satisfactorily elucidated. Recent animal and in vitro data suggested that the transcription factor cAMP-responsive element modulator (CREM) alpha plays a critical role in T cells´ disturbed IL-2 production in suboptimal zinc conditions. However, its role in the human aging process and the possibility of influencing this detrimental process by short-term zinc supplementation have not yet been evaluated.ResultsComparing peripheral lymphocytes of 23 young and 31 elderly subjects with either high, intermediate, or deficient zinc status, we observed zinc-dependent regulation of the IL-2 production mediated by the transcription factor CREM alpha. For the first time in humans, we report a mutual relationship between low zinc levels, high CREM alpha expression, subsequent impaired IL-2 production, and vice versa. Remarkably, an average of only 6 days of in vivo zinc supplementation to zinc-deficient seniors was sufficient to rapidly improve zinc status, reverse CREM alpha overexpression, and counteract subsequent low IL-2 production rates.ConclusionsOur ex vivo and in vivo data identify zinc deficiency-mediated CREM alpha overexpression as a key cellular mechanism underlying impaired IL-2 production in the elderly and point toward the use of zinc as a rapidly immune-enhancing add-on nutraceutical in geriatric therapy.Graphical abstractDuring the aging process, there is a progressive decrease in zinc status, which in turn leads to overexpression of the transcription factor CREMmathrm{alpha } in peripheral lymphocytes. CREMα is a negative regulator of the IL-2 gene, the overexpression of which dramatically limits adequate IL-2 production. This deleterious mechanism can be counteracted by short-term oral zinc administration, which can adjust IL-2 production in old, zinc-deficient individuals to a level similar to that of young adults.

Oral adverse events due to zinc deficiency after pancreaticoduodenectomy requiring continuous intravenous zinc supplementation: a case report and literature review

BackgroundZinc is mainly absorbed in the duodenum and proximal jejunum, which are removed during pancreaticoduodenectomy (PD). Little is known about the adverse oral events and skin disorders caused by zinc deficiency after PD. Herein, we reviewed studies on the development of zinc deficiency after PD and reported about a patient with zinc deficiency after PD who required home intravenous zinc replacement.Case presentationA 73-year-old woman with glossitis, taste disorder, and acrodermatitis enteropathica-like eruption on her fingers presented to the Division of Dentistry and Oral Surgery 69 days after PD. Her serum zinc level markedly decreased to 30 μg/dL. Oral zinc administration was inadequate to treat hypozincemia after PD; therefore, multi-trace elements were injected intravenously during readmission. Her serum zinc levels recovered, and her lesions gradually improved. Furthermore, a central venous port was implanted to maintain normal serum zinc levels, and she continued self-injecting zinc at home.ConclusionsZinc deficiency after PD rarely occurs. The clinical oncologist community, including dentists responsible for the oral care of cancer patients, should be aware of the oral adverse events, such as dysgeusia, glossitis, and oral pain, associated with zinc deficiency after cancer surgery and that induced by chemotherapy or head and neck radiation therapy.

S1354 Modification of the Tight Junctional Barrier in Human Duodenal Mucosal by Oral Zinc Administration in a Patient-Based Study: RNA-Seq and Western Immunoblot Analyses

Introduction: Mucosal barrier function is targeted in a wide variety of GI disease. Celiac disease, IBD, GI malignancies, sepsis and a wide variety of GI microbial infectious diseases all compromise the GI barrier. The tight junctional (TJ) complex is pivotal in this regard. The ability to safely modify the TJ complex and reduce its leakiness could be prophylactically and/or therapeutically useful. Methods: Patients 18-80 years of age presenting for endoscopic medical surveillance of gastroesophageal disorders but free of current small bowel disease were recruited for study. Patients were instructed to administer orally either a zinc-gluconate medication (12 patients) (26 mg elemental zinc) or a sodium gluconate placebo (11 patients), BID, for 14 days immediately prior to their EGD. During their EGD, standard duodenal bulb biopsies were taken for Western immunoblot analysis and for mRNA analysis. Biopsies were immediately flash frozen on dry ice in the procedures room and stored at -195oC for subsequent extraction. For protein studies, biopsies were homogenized in lysis buffer, sonicated and then analyzed by PAGE and Western immunoblot using a variety of antibodies to TJ proteins. Analysis of the biopsy transcriptome was performed by high-throughput RNA-seq. Results: Transcriptome analysis of over 20,000 genes revealed upregulation of many known zinc-regulated genes such as metallothioneins A, B, F, G, H, L, and M. The TJ barrier gene, occludin (OCLN), was also upregulated. Enrichment analysis using GSEA showed zinc upregulating several gene ontology (GO) biological processes as well as cellular components and pathways (Reactome). These included Zinc Ion Homeostasis (GO), Response to Zinc Ion (GO), Cell Junction Organization (Reactome), Cell-Cell Junction Assembly (GO), and Tight Junction (GO). Western immunoblot analyses showed statistically significant upregulation (two-tailed t-test) of the TJ proteins, claudin-2 and tricellulin, in mucosal biopsies of the zinc-treated group. Claudins -3 and -5 showed significant upregulations, and claudin-7, a significant down regulation, in a one-tailed t-test. Claudins -1, -4 and -18 showed no trend regarding a zinc-induced change. Conclusion: This is the first evidence of intended modification of TJ complexes in humans in situ. The results follow on a large body of published literature showing zinc-induced TJ changes and improved barrier function in a variety of human epithelial cell culture and animal models.

​Expression Profiling of Cytokine-related Genes in the Small Intestine of Healthy Pre and Post-weaned Piglets Administered Orally with Probiotic and Zinc

Background: The present study was designed to evaluate alterations in the immunological status of the small intestine after dietary inclusion of probiotic and zinc in pre and post-weaned piglets. Methods: For the present study, 18 healthy Large White Yorkshire (LWY) piglets, irrespective of sex, were divided into three different age groups [pre-weaning (20 days old, n = 3), weaning (30 days old, n = 3) and post-weaning (60 days old, n = 3)]. The piglets were weaned at 28 days of age. They were divided into control group (C) fed with basal diet and treatment group (T) fed with combined probiotic and zinc oral supplement along with the basal diet. A probiotic mixture consisted of Lactobacillus acidophilus, Lactobacillus rhamnosus and Bifidobacterium longum (1.25x109cfu/d for 10 days) along with zinc supplement (ZnO @ 2000 ppm/d for 10 days) administered orally to the treatment group of piglets. Result: The relative expression of TNF-α, IL-1β and IL-6 genes was significantly higher (P less than 0.05) in the treatment group of piglets as compared to the control group. However, the expression of IL-8, IL-12p40 and IL-18 genes were significantly lower (P less than 0.05) after oral administration of probiotic and zinc to the piglets.

Zinc supplementation prevents the development of thymic involution induced by tumor growth in mice

Aim. The aim of this study was to investigate the influence of zinc supplementation on the development of thymic involution during the growth of transplantable tumor in mice. Materials and methods. Inbred C3HA mice after subcutaneous syngeneic hepatoma 22a inoculation received zinc sulfate with drinking water. After 3 weeks of tumor growth animals were killed, and evaluated for zinc content in serum blood samples, thymus status and parameters of tumor growth. Results. At the 21 day of tumor 22a growth weight and cellular content of the thymus were decreased by 3 times and endogenous zinc content in samples of blood serum was decreased by 1,9 times. Oral zinc sulfate supplementation at concentration of 22 mkg/ml in drinking water during 3 weeks, started from the first day after tumor inoculation, increased thymus weight and cellularity as well as serum zinc content. At the same time, it did not influence tumor size and survival rate of mice with hepatoma 22a. As a possible mechanism of zinc action, we studied the influence of zinc supplementation on the activity of two anti-oxidative defense enzymes: Cu,Zn-superoxide dismutase and catalase in the thymus. Zinc supplementation had no influence on these parameters, both remained at a higher level in tumor-bearing mice. Conclusion. Oral zinc supplementation in hepatoma 22a bearing mice induced retards the development of thymic involution with no influence on the tumor growth per se. The study allows to suggest that oral zinc administration may be considered as a prospective strategy for thymus reconstitution in oncology patients.

Orexigenic action of oral zinc: metabolomic analysis in the rat hypothalamus.

We previously reported an orexigenic action of oral zinc administration in male Sprague-Dawley (SD) rats during an early stage of feeding with a zinc-deficient diet, without decreased zinc concentrations in tissues. The overall conclusion was that orally but not intraperitoneally administered zinc stimulates food intake in short-term zinc-deficient-diet fed rats. We here investigate the mechanism of the orexigenic action of zinc using GC-MS/MS-targeted metabolomic analysis in the rat hypothalamus. Four-week-old, male SD/Slc rats were used, and after 2days of feeding with a zinc-deficient diet, 3mg of ZnSO4 in 5mL saline solution were administered to each rat either orally or intraperitoneally. Three hours after administration, the rats were sacrificed and the hypothalamus were excised and analyzed. We found that the oral administration group showed increased concentrations of 3-aminopropanoic acid (β-alanine), hypotaurine, dopamine, and biotin. In light of metabolomic analysis of these results, we indicate directions for further research.

Prevalence of Zinc Deficiency and Effect of Zinc Supplementation on Prevention of Acute Respiratory Infections: A Non Randomized Open Label Study

Background: Routine zinc supplementation is a potential intervention for the prevention of acute lower respiratory infections in developing countries. However discrepant findings from recent randomized trials remain unexplained. Methods: Single centre, single arm, prospective non-randomized, open label interventional study, of effect of zinc supplementation in zinc deficient children aged 6 months to 5 years. 465 healthy children aged 6 months to 5 years were enrolled in the study. The primary outcome was the prevalence of serum zinc deficiency. Children having zinc deficiency were recruited for the study of effect of oral administration of zinc 20 mg for 2 weeks. The secondary outcomes were incidence and duration of acute upper respiratory and acute lower respiratory infections per child-year and side effects after giving zinc therapy. Results: There was significant difference in mid arm circumference in between zinc deficient and non-zinc deficient groups (p < 0.001). Also the number of episodes of acute upper respiratory infections (AURI) and mean duration of AURI and acute lower respiratory infections (ALRI) was significantly different in the two groups (p < 0.001). There was no significant difference in ALRI episodes in two groups. After zinc supplementation in zinc deficient children, there was significant decrease in the number of episodes and mean duration of AURI (p < 0.001) and ALRI (p < 0.001) in six months after supplementation as compared to preceding six months before supplementation. Conclusion: This study sheds light on the efficacy of short course prophylactic zinc supplementation in reducing the burden of ARI among zinc deficient children. Future studies should assess the effectiveness of delivering prophylactic zinc supplementation at scale, comparing the feasibility and cost benefit of short course and continuous regimens. Clinical Trial Number: As it was a Non Randomized observational single arm study, study was not registered. Only RCT needs to be registered. Funding Statement: This study was funded by All India Institute of Medical Sciences (AIIMS), Manuscript Jodhpur, India, as a part of Intramural project conducted in the department of Pediatrics, AIIMS Jodhpur. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: The study was approved by Institutional Ethics committee of All India Institute of Medical Sciences, Jodhpur, India. The study was conducted in accordance with ICH-GCP and other applicable regulatory guidelines.

Potential role of zinc in the visceromegaly regression and recovery of hematological parameters during treatment of visceral leishmaniasis in children from an endemic area.

ABSTRACTLeishmaniasis is a disease complex with various clinical symptoms caused by different species of parasites of the genus Leishmania. The visceral form of the disease, characterized by severe symptoms is fatal, if not treated. The high toxicity of current antileishmanial drugs and the need for long-term treatment make the therapy complicated, especially in a large number of infected children. Hence, the search for new therapies must be intensified. Oral administration of the trace element zinc has been considered in alternative treatments against different clinical forms of leishmaniasis. This study revealed that the administration of zinc in children with visceral leishmaniasis, during treatment with amphotericin B or glucantime, accelerates the regression of the spleen enlargement without interfering with the recovery of hematological parameters.

Clarification of the Mechanism Involved in Orexigenic Action by Oral Zinc Ingestion

We investigated the role of zinc in regulation of food intake using male SD rats during early-stage of zinc deficiency (the 3rd day of the feeding) without decreased zinc concentrations in tissues (hypothalamus and liver). As a result, we found that orally but not intraperitoneal administered zinc stimulates food intake in the short-term zinc-deficient rats. The mRNA expressions of hypothalamic peptides, such as orexin (OX) and neuropeptide Y (NPY), were increased after oral administration of zinc to increase food intake. Pretreatment with an antagonist for the NPY Y1 receptor or the orexin OX1 receptor blocked orexigenic activity by zinc administration. The stimulation of food intake by oral administration of zinc was also abolished by vagotomy. Taken together, our results indicate that zinc stimulates food intake in short-term zinc-deficient rats through the afferent vagus nerve followed by activating the hypothalamic peptide associated with food intake regulation. This study showed the first evidence that gastrointestinal zinc signal is indispensable for the food appetite induction in the experimentally anorexigenic rat. However, since it has not yet been clarified the mechanism involved in zinc sensing by the epithelial membrane of the gastrointestinal tract, further detailed investigations are necessary.

Experimental Research Showing the Reduction of Naloxone-Place Aversion by Oral Zinc Administration in Rats.

Previous studies showed the attenuation of both morphine-dependence and morphine-place preference by zinc. Conditioned place preference and aversion are experimental models frequently used to test the reward-stimulating, respectively the aversive effects induced by different stimuli or substances. Addictive substances usually induce place preference (exhibit reward-stimulating properties), while their antagonists determine place-avoidance (aversion). The present study aimed to assess the effect determined by zinc sulphate oral administration (2 and 4mg/kg/day, 14days, prior to habituation) on the place aversion induced by two naloxone doses (1.5 and 2.5mg/kg/administration). The results show a robust, dose-dependent reduction of the aversion determined by both naloxone doses (the aversion induced by 1.5mg/kg naloxone was reduced with 15%-the lower zinc dose and with 24%-the higher zinc dose; the aversion induced by 2.5mg/kg naloxone was reduced with 16%-the lower zinc dose and with 29%-the higher zinc dose). This represents a new proof of the interactions between zinc and opioidergic system and a further argument for dietary zinc supplementation in patients on opioids for cancer-related chronic pain.

The beneficial effects of zinc on diabetes-induced kidney damage in murine rodent model of type 1 diabetes mellitus

Diabetes mellitus is a chronic multi-factorial metabolic disorder resulting from impaired glucose homeostasis. Zinc is a key co-factor for the correct functioning of anti-oxidant enzymes. Zinc deficiency therefore, impairs their synthesis, leading to increased oxidative stress within cells. Zinc deficiency occurs commonly in diabetic patients. The aim of this study is to investigate the effects of varying concentrations of zinc on diabetic nephropathy (DN) and the underlying mechanisms involved. FVB male mice aged 8 weeks were injected intraperitoneally with multiple low-dose streptozotocin at a concentration of 50mg/kg body weight daily for 5 days. Diabetic and age-matched control mice were treated with special diets supplemented with zinc at varying concentrations (0.85mg/kg, 30mg/kg, 150mg/kg) for 3 months. The mice were fed with zinc diets to mimic the process of oral administration of zinc in human. Zinc deficiency to some extent aggravated the damage of diabetic kidney. Feeding with normal (30mg/kg zinc/kg diet) and especially high (150mg/kg zinc/kg diet) concentration zinc could protect the kidney against diabetes-induced damage. The beneficial effects of zinc on DN are achieved most likely due to the upregulation of Nrf2 and its downstream factors NQO1, SOD1, SOD2. Zinc upregulated the expression of Akt phosphorylation and GSK-3β phosphorylation, resulting in a reduction in Fyn nuclear translocation and export of Nrf2 to the cytosol. Thus, regular monitoring and maintaining of adequate levels of zinc are recommended in diabetic individuals in order to delay the development of DN.

Coadministration of puerarin (low dose) and zinc attenuates bone loss and suppresses bone marrow adiposity in ovariectomized rats

AimsPuerarin is a phytoestrogen that shows osteogenic effects. Meanwhile, zinc stimulates bone formation and inhibits bone resorption. The study aims to investigate the effects of coadministration of puerarin (low dose) and zinc on bone formation in ovariectomized rats. Materials and methodsCo-administration or use alone of puerarin (low dose) and/or zinc were gavaged in OVX rats. The estrogen-like effects were detected by the uterus weight, the histologic observation and the IGF-1 protein expression. The osteogenic effects were determined by bone histomorphometric and mechanical parameters, osteogenic and adipogenic blood markers, and so on. Key findingsThe results showed that oral administration of puerarin (low dose) plus zinc didn't significantly increase uterus weight. The glandular epithelial of endometrium had no proliferation and no protein expression of IGF-1. Moreover, co-administration attenuated bone loss and biomechanical decrease more than single use of puerarin or zinc (p<0.05). Next, combined administration of puerarin and zinc promoted the serological level of osteocalcin, bone marrow stromal cell (BMSC) proliferation, and the expression of alkaline phosphatase (ALP), and suppressed the serological level of adiponectin and adiposity in bone marrow (BM). SignificanceIn conclusion, co-administrated puerarin (low dose) and zinc can partially reverse OVX-induced bone loss and suppress the adiposity of BM in rats, which shed light on the potential use of puerarin and zinc in the treatment of osteoporosis.

Effects of oral zinc administration on long-term ipsilateral and contralateral testes damage after experimental testis ischaemia-reperfusion.

The purpose of this study was to examine potential long-term post-torsion changes that can occur in the histopathology, biochemistry and spermatogenesis of both torsioned and nontorsioned opposite testes. The study also determines the effect of zinc (Zn) administration on the testicular torsion/detorsion (T/D) damage on both testes. Forty-eight male rats, divided equally into eight groups: (SHAM), (SHAM+,Zn+), (T/D+, Zn- 1month), (T/D+,Zn- 2months), (T/D+,Zn- 3months), (T/D+,Zn+ 1months), (T/D+,Zn+ 2months), (T/D+,Zn+ 3months), have been used. Drug administration was carried out by adding 100μg (0.016ml/rat) Zn per rat to drinking water in related groups. Testicular damage decreased superoxide dismutase (SOD) and glutathione (GSH) and increased malondialdehyde (MDA) in the testis tissues of rats, while Zn administration increased SOD and GSH and decreased MDA in the testis tissues in comparison with the SHAM group. The beneficial effect of zinc sulphate was more evident on the nonrotated testis than the rotated testis. In the histopathological study, a significant decrease in torsion and detorsion injuries was observed in the treatment groups compared to the torsion and detorsion groups. We found a protective effect of zinc sulphate on oxidative stress as a result of T/D injuries in rats, especially for the nonrotated testis; results were supported histopathologically.

Oral treatment with a zinc complex of acetylsalicylic acid prevents diabetic cardiomyopathy in a rat model of type-2 diabetes: activation of the Akt pathway.

BackgroundType-2 diabetics have an increased risk of cardiomyopathy, and heart failure is a major cause of death among these patients. Growing evidence indicates that proinflammatory cytokines may induce the development of insulin resistance, and that anti-inflammatory medications may reverse this process. We investigated the effects of the oral administration of zinc and acetylsalicylic acid, in the form of bis(aspirinato)zinc(II)-complex Zn(ASA)2, on different aspects of cardiac damage in Zucker diabetic fatty (ZDF) rats, an experimental model of type-2 diabetic cardiomyopathy.MethodsNondiabetic control (ZL) and ZDF rats were treated orally with vehicle or Zn(ASA)2 for 24 days. At the age of 29–30 weeks, the electrical activities, left-ventricular functional parameters and left-ventricular wall thicknesses were assessed. Nitrotyrosine immunohistochemistry, TUNEL-assay, and hematoxylin-eosin staining were performed. The protein expression of the insulin-receptor and PI3K/AKT pathway were quantified by Western blot.ResultsZn(ASA)2-treatment significantly decreased plasma glucose concentration in ZDF rats (39.0 ± 3.6 vs 49.4 ± 2.8 mM, P < 0.05) while serum insulin-levels were similar among the groups. Data from cardiac catheterization showed that Zn(ASA)2 normalized the increased left-ventricular diastolic stiffness (end-diastolic pressure–volume relationship: 0.064 ± 0.008 vs 0.084 ± 0.014 mmHg/µl; end-diastolic pressure: 6.5 ± 0.6 vs 7.9 ± 0.7 mmHg, P < 0.05). Furthermore, ECG-recordings revealed a restoration of prolonged QT-intervals (63 ± 3 vs 83 ± 4 ms, P < 0.05) with Zn(ASA)2. Left-ventricular wall thickness, assessed by echocardiography, did not differ among the groups. However histological examination revealed an increase in the cardiomyocytes’ transverse cross-section area in ZDF compared to the ZL rats, which was significantly decreased after Zn(ASA)2-treatment. Additionally, a significant fibrotic remodeling was observed in the diabetic rats compared to ZL rats, and Zn(ASA)2-administered ZDF rats showed a similar collagen content as ZL animals. In diabetic hearts Zn(ASA)2 significantly decreased DNA-fragmentation, and nitro-oxidative stress, and up-regulated myocardial phosphorylated-AKT/AKT protein expression. Zn(ASA)2 reduced cardiomyocyte death in a cellular model of oxidative stress. Zn(ASA)2 had no effects on altered myocardial CD36, GLUT-4, and PI3K protein expression.ConclusionsWe demonstrated that treatment of type-2 diabetic rats with Zn(ASA)2 reduced plasma glucose-levels and prevented diabetic cardiomyopathy. The increased myocardial AKT activation could, in part, help to explain the cardioprotective effects of Zn(ASA)2. The oral administration of Zn(ASA)2 may have therapeutic potential, aiming to prevent/treat cardiac complications in type-2 diabetic patients.

Zinc directly stimulates cholecystokinin secretion from enteroendocrine cells and reduces gastric emptying in rats

Zinc, an essential mineral element, regulates various physiological functions such as immune responses and hormone secretion. Cholecystokinin (CCK), a gut hormone, has a role in protective immunity through the regulation of gastrointestinal motility, appetite, and inflammatory response. Here, we examined the effect of zinc on CCK secretion in STC-1 cells, an enteroendocrine cell line derived from murine duodenum, and in rats. Extracellular zinc triggered CCK secretion accompanied with increased intracellular Ca2+ and Zn2+ mobilization in STC-1 cells. Zinc-induced CCK secretion was abolished in the absence of intracellular Zn2+ or extracellular calcium. Upon inhibition of transient receptor potential ankyrin 1 (TRPA1), extracellular zinc failed to increase intracellular Ca2+ and subsequent CCK secretion. In rats, oral zinc administration decreased gastric emptying through the activation of CCK signaling. These results suggest that zinc is a novel stimulant for CCK secretion through the activation of TRPA1 related to intracellular Zn2+ and Ca2+ mobilization.

Abstract 13376: Oral Treatment With a Zinc Complex of Acetylsalicylic Acid Prevents Diabetic Cardiomyopathy in a Rat Model of Type 2 Diabetes

Introduction: Type 2 diabetic patients are at an increased risk of cardiomyopathy and heart failure is a major cause of death amongst these patients. Growing evidence indicates that proinflammatory cytokines can cause sustained development of insulin resistance and anti-inflammatory medications may reverse this process. Hypothesis: We investigated the effects of an oral administration of zinc and acetylsalicylic acid in the form of bis(aspirinato)zinc(II) complex Zn(ASA)2 on different aspects of cardiac damage in the Zucker diabetic rat (ZDF), an experimental model of type 2 diabetic cardiomyopathy. Methods: The nondiabetic control and the diabetic ZDF rats were pretreated orally with vehicle or Zn(ASA)2 for 24 days. At the age of 30-32 weeks, both the electrical activity and the left ventricular (LV) structural/functional parameters were assessed via electrocardiogram and pressure volume (PV) conductance catheter system. Results: The Zn(ASA)2 treatment significantly decreased the blood glucose concentration (39.6±3.1 vs 50.4±2.6 mM), normalized the impaired LV contractility index (Emax 3.7±0.4 vs 1.9±0.6 mmHg/μl), the passive LV stiffness (end diastolic PV relationship: 0.064±0.008 vs 0.084±0.014 mmHg/μl), and the diastolic dysfunction (LV end diastolic pressure: 6.5±0.6 vs 7.9±0.7 mmHg). Furthermore, the ECG revealed a restoration of the prolonged corrected QT intervals (63±3 vs 83±4 ms, p&lt;0.05) by Zn(ASA)2. A histological examination revealed an increase in the cardiomyocytes transverse cross section area in diabetic rats compared to the controls, which was significantly decreased after Zn(ASA)2. Furthermore, a significant increase in fibrotic formation was observed in the diabetic rats compared to controls, and Zn(ASA)2 administration showed similar collagen content in the ZDF+Zn(ASA)2 rats and in the nondiabetics. A significant increase in the density of TUNEL positive cell nuclei in the diabetic hearts, indicating DNA fragmentation, was significantly decreased by Zn(ASA)2. Additionally, in the diabetic heart, Zn(ASA)2 significantly decreased nitrotyrosine formation. Conclusions: The oral administration of Zn(ASA)2 may have therapeutic potential with the aim of preventing cardiac complications in type 2 diabetic patients.

Effect of Zinc Supplementation on GH, IGF1, IGFBP3, OCN, and ALP in Non-Zinc-Deficient Children

Objective: Because most publications on growth and development deal with children with zinc deficiency, we decided to study the effects of this micronutrient on the secretion of growth hormone (GH), insulin-like growth factor 1 (IGF1), insulin-like growth factor binding protein 3 (IGFBP3), osteocalcin (OCN), and alkaline phosphatase (ALP) in healthy and eutrophic children. This study is original because the methodology was unique.Methods: Forty schoolchildren participated in the study, 17 females and 23 males, aged 8 and 9 years. The study was carried out during a 3-month period. It was characterized as a triple-blind randomized controlled trial. The children were divided in a control group (20 schoolchildren using 10% sorbitol) and experimental group (20 schoolchildren using zinc). All were submitted to oral zinc supplementation (10 mg Zn/day) and venous zinc administration (0.06537 mg Zn/kg of body weight). Blood samples were collected at 0, 60, 120, 180, and 210 min. All schoolchildren were also submitted to anthropometric, clinical, and dietetic assessments as well as biochemistry analyses.Results: Oral zinc supplementation in the experimental group (1) stimulated an increase in the consumption of protein and fat (p = 0.0007, p < 0.0001, p < 0.0001, respectively), (2) increased basal serum zinc (p < 0.0001), (3) increased plasma ALP (p = 0.0270), and (4) showed a positive correlation for IGF1, IGFBP3, and OCN, comparing before and after oral zinc supplementation (p = 0.0011, p < 0.0001, p < 0.0446, respectively). During zinc administration, plasma IGF1 and IGFBP3 increased significantly in the experimental group (p = 0.0468, p < 0.0001, respectively). Plasma GH increased in the experimental group but without statistical difference comparing before and after oral zinc supplementation.Conclusions: Zinc supplementation stimulated an increase in the consumption of some macronutrients and basal serum zinc and improved plasma alkaline phosphatase levels. Zinc administration increased hormones of the GH-IGF1 system.

PP036-SUN: Effect of Oral Zinc Administration on Clinical Improvement of Severe Head Trauma Patients in ICU: A Pilot Study

PP036-SUN: Effect of Oral Zinc Administration on Clinical Improvement of Severe Head Trauma Patients in ICU: A Pilot Study