Zinc Supplementation Improves ZIP14 (SLC39A14) Levels in Cerebral Cortex Suppressed by icv-STZ Injection.

Introduction: Metabolic dysfunctions are critical in the pathology of Alzheimer's disease. Impaired zinc homeostasis, in particular, is a significant issue in this disease that has yet to be explained. Gene expression of ZIP14 in brain tissue has been previously reported. But to date, only one study has reported reduced ZIP14 levels in aged brain tissue. We investigated how dietary zinc deprivation and supplementation impact ZIP14 levels in the cerebral cortex in rats with sporadic Alzheimer's disease (sAH) produced by intracerebroventricular streptozotocin (icv-STZ). Impaired zinc homeostasis, in particular, is a significant issue with this condition that has yet to be elucidated. Methods: Animals were divided into 5 groups in equal numbers (n=8): Sham 1 group: icv received artificial cerebrospinal fluid (aCSF); Sham 2 group: retrieved icv aCSF and intraperitoneal (ip) saline, STZ group: received 3 mg/kg icv-STZ; STZ-Zn-Deficient group: received 3 mg/kg icv-STZ and fed a zinc-deprived diet; STZ-Zn-Supplemented: It received 3 mg/kg icv-STZ and ip zinc sulfate (5 mg/kg/day ZIP 14 levels (ng/L) in cortex tissue samples taken from animals sacrificed under general anesthesia were determined by ELISA at the final stage of the experimental applications. Results: Decreased ZIP14 levels in the sporadic Alzheimer's group were severely by zinc deficiency. Zinc supplementation treated the reduction in ZIP14 levels. Conclusion: The results of the current study show that ZIP14 levels in cerebral cortex tissue, which are suppressed in the experimental rat Alzheimer model and are even more critically reduced in zinc deficiency, can be restored by zinc supplementation.

Marginal Maternal Zinc Deficiency Produces Liver Damage and Altered Zinc Transporter Expression in Offspring Male Rats.

The aim of this study was to investigate how zinc deficiency and supplementation affect liver markers including autotaxin, kallistatin, endocan, and zinc carrier proteins ZIP14 and ZnT9 in rats exposed to maternal zinc deficiency. Additionally, the study aimed to assess liver tissue damage through histological examination. A total of forty male pups were included in the research, with thirty originating from mothers who were given a zinc-deficient diet (Groups 1, 2, and 3), and the remaining ten born to mothers fed a standard diet (Group 4). Subsequently, Group 1 was subjected to a zinc-deficient diet, Group 2 received a standard diet, Group 3 received zinc supplementation, and Group 4 served as the control group without any supplementation. Upon completion of the experimental phases of the study, all animals were sacrificed under general anesthesia, and samples of liver tissue were obtained. The levels of autotaxin, kallistatin, endocan, ZIP 14, and ZnT9 in these liver tissue samples were determined using the ELISA technique. In addition, histological examination was performed to evaluate tissue damage in the liver samples. In the group experiencing zinc deficiency, both endocan and autotaxin levels increased compared to the control group. With zinc supplementation, the levels of endocan and autotaxin returned to the values observed in the control group. Similarly, the suppressed levels of kallistatin, ZIP14, and ZnT9 observed in the zinc deficiency group were reversed with zinc supplementation. Likewise, the reduced levels of kallistatin, ZIP14, and ZnT9 seen in the zinc deficiency group were rectified with zinc supplementation. Moreover, the application of zinc partially ameliorated the heightened liver tissue damage triggered by zinc deficiency. This study is the pioneering one to demonstrate that liver tissue dysfunction induced by a marginal zinc-deficient diet in rats with marginal maternal zinc deficiency can be alleviated through zinc supplementation.

The relationship between beta cell activation and SLC30A8/ZnT8 levels of the endocrine pancreas and maternal zinc deficiency in rats.

OBJECTIVES: Zinc, which is found in high concentrations in the ß-cells of the pancreas, is also a critical component for the endocrine functions of the pancreas. SLC30A8/ZnT8 is the carrier protein responsible for the transport of zinc from the cytoplasm to the insulin granules. The aim of this study was to investigate how dietary zinc status affects pancreatic beta cell activation and ZnT8 levels in infant male rats born to zinc-deficient mothers. METHODS: The study was performed on male pups born to mothers fed a zinc-deficient diet. A total of 40 male rats were divided into 4 equal groups. Group 1: In addition to maternal zinc deficiency, this group was fed a zinc-deficient diet. Group 2: In addition to maternal zinc deficiency, this group was fed a standard diet. Group 3: In addition to maternal zinc deficiency, this group was fed a standard diet and received additional zinc supplementation. Group 4: Control group. Pancreas ZnT8 levels were determined by ELISA method and insulin-positive cell ratios in ß-cells by immunohistochemistry. RESULTS: The highest pancreatic ZnT8 levels and anti-insulin positive cell ratios in the current study were obtained in Group 3 and Group 4. In our study, the lowest pancreatic ZnT8 levels were obtained in Group 1 and Group 2, and the lowest pancreatic anti-insulin positive cell ratios were obtained in Group 1. CONCLUSION: The results of the present study; in rats fed a zinc-deficient diet after maternal zinc deficiency has been established shows that ZnT8 levels and anti-insulin positive cell ratios in pancreatic tissue, which is significantly suppressed, reach control values with intraperitoneal zinc supplementation.

Zinc Ameliorates Nogo-A Receptor and Osteocalcin Gene Expression in Memory-Sensitive Rat Hippocampus Impaired by Intracerebroventricular Injection of Streptozotocin.

Metabolic dysfunction is a critical step in the etiopathogenesis of Alzheimer's disease. In this progressive neurological disorder, impaired zinc homeostasis has a key role that needs to be clarified. The aim of this study was to investigate the effect of zinc deficiency and administration on hippocampal Nogo-A receptor and osteocalcin gene expression in rats injected with intracerebroventricular streptozotocin (icv-STZ). Forty male Wistar rats were divided into 5 groups in equal numbers: Sham 1 group received icv artificial cerebrospinal fluid (aCSF); Sham 2 group received icv a CSF and i.p. saline; STZ group received 3 mg/kg icv STZ; STZ-Zn-deficient group received 3 mg/kg icv STZ and fed a zinc-deprived diet; STZ-Zn-supplemented group received 3 mg/kg icv STZ and i.p. zinc sulfate (5 mg/kg/day). Hippocampus tissue samples were taken following the cervical dislocation of the animals under general anesthesia. Nogo-A receptor and osteocalcin gene expression levels were determined by real-time-PCR method. Zinc supplementation attenuated the increase in hippocampal Nogo-A receptor gene expression, which was significantly increased in zinc deficiency. Again, zinc supplementation upregulated the intrinsic protective mechanisms of the brain by activating osteocalcin-expressing cells in the brain. The results of the study show that zinc has critical effects on Nogo-A receptor gene expression and hippocampal osteocalcin gene expression levels in the memory-sensitive rat hippocampus that is impaired by icv-STZ injection. These results are the first to examine the effect of zinc deficiency and supplementation on hippocampal Nogo-A receptor and osteocalcin gene expression in icv-STZ injection in rats.

The effects of resveratrol and melatonin on biochemical and molecular parameters in diabetic old female rat hearts.

The roles of melatonin and resveratrol-enhanced activation of SIRT1 (silent information regulator 1), GLUT4 (glucose transporter type 4), and PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) in mediating the protective effects on the heart in aged female rats with streptozotocin-induced diabetes were investigated. 16-month-old 48 Wistar female rats were separated into 8 groups with equal numbers. Group 1: Control, Group 2: Resveratrol Control, Group 3: Melatonin Control, Group 4: Resveratrol and Melatonin Control, Group 5: Diabetes, Group 6: Diabetes Resveratrol, Group 7: Diabetes Melatonin, Group 8: Diabetes Resveratrol and Melatonin. A single dose of 40 mg/kg intraperitoneal streptozotocin was injected into the rats of Groups 5, 6, 7, and 8 to induce experimental diabetes. Blood glucose levels were measured from the tail veins of the animals six days after the injections, using a diagnostic glucose kit. Rats with a blood glucose levels ≥300 mg/dl were considered diabetic. 5 mg/kg/day of resveratrol (intraperitoneal) and melatonin (subcutaneous) were administered for four weeks. At the end of the applications, SIRT1, GLUT4, PGC-1α gene expression as well as MDA and GSH levels in the heart tissues were determined by the PCR method from heart tissue samples taken under general anesthesia. The findings of our study show that suppressed antioxidant activity and decreased GLUT4, SIRT1, and PGC-1α gene expression in heart tissue can be reversed by the combination of resveratrol, melatonin, and resveratrol + melatonin in a diabetic aged female rat model. Resveratrol and melatonin supplementation may have a protective effect on cardiac functions in the diabetic aged female rat model.

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-GSK3ß, 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 pinealectomy and melatonin supplementation on metallothionein, ZnT2, ZIP2, ZIP4 and zinc levels in rat small intestine.

We investigated the relations among levels of metallothionein (MT); zinc (Zn) transport proteins, ZnT2, ZIP2 (ZRT and IRT-like proteins); and ZIP4, which enable Zn absorption in the small intestine of rats. We also investigated tissue Zn levels in the small intestine. We used four groups of adult male rats: group 1, control; group 2, pinealectomy (Px); group 3, Px + melatonin (MEL); group 4, MEL only. Animals in groups 3 and 4 were administered 5 mg/kg/day MEL for four weeks. At the end of the study, all animals were sacrificed and samples of duodenum, jejunum and ileum were harvested to analyze ZnT2, ZIP2, ZIP4 and MT levels using immunohistochemistry, and tissue Zn levels were measured by atomic absorption spectrophotometry. The lowest ZnT2 levels in the duodenum, jejunum and ileum, and the lowest ZIP2 levels in the duodenum and ileum were found in group 2. The lowest ZIP4 levels were found in the duodenum and jejunum, and the lowest MT levels in the duodenum and ileum were found in group 2. The highest MT values in the ileum were found in group 4. We found that ZnT2, ZIP2, ZIP4 and MT levels were reduced in the ileum compared to controls following Px, but levels approached control values after MEL administration. By its effects on ZnT2, ZIP2, ZIP4 and MT levels, MEL participates in the absorption of Zn in the rat small intestine.

Hearing stimulation of the pediatric patient with congenital aural atresia: surgical and audiological evaluation of 38 patients.

The aim of this work is to stress the importance of and discuss the timing and options for the treatment of congenital aural atresia (CAA), including non-surgical alternative treatment modalities and amplification, and to report the audiological and surgical results of a series of patients. Thirty-eight children with CAA were evaluated with regard to hearing and anatomical anomalies accompanying CAA: the state of the ossicles and the facial nerve, postoperative complications and audiological results. The ages of the patients ranged between 4 and 18 years, with a mean of 10 years. All underwent surgical treatment; 32 had unilateral atresia, while 6 had bilateral atresia. The mean follow-up duration was 7 months. The facial canal was dehiscent in 36.8% of cases. In 70.2% cases, the malleus and incus were present as an ossicular mass, fixed and attached to the atretic bone. The stapes was normal in 97.3% of the patients; in 2.7% the suprastructure was deformed. The success rate, defined as an air-bone gap of 20 dB or less, was 63.1% in this series of patients. If atresia is bilateral, very early hearing stimulation to prevent the maldevelopment of children's speech and cognitive skills is of the utmost importance. In unilateral cases, surgery may be postponed until early adulthood, when the patient is able to make his/her own decision and cooperate in the treatment and postoperative aspects.

[Endonasal phototherapy in the treatment of allergic rhinitis]. / Alerjik rinit tedavisinde endonazal fototerapi.

OBJECTIVES: In this study, we assessed the effect of endonasal phototherapy on quality of life, nasal obstruction and the other symptoms in allergic rhinitis with visual analog scale (VAS), sinonasal outcome test-20 (SNOT-20), and acoustic rhinometry. PATIENTS AND METHODS: Twenty-four patients (6 males, 18 females; mean age 41.3±13.0 years; range 20 to 60 years) suffering allergic rhinitis refractory to anti allergic drugs for at least two years were enrolled in the study. Each patient underwent a total of six sessions of endonasal phototherapy with Rhinolight (Rhinolight Ltd, Szeged, Hungary) performed three times a week for two weeks. During course of the investigation, additional therapy was not applied to any of the patients. Before and one month after treatment, patients completed visual analog scale and SNOT-20 forms and nasal obstruction was evaluated with acoustic rhinometry. RESULTS: After the treatment, the mean VAS score and the mean total SNOT-20 score were found lower than the results before the therapy (p=0.0001, p=0.0001). A significant decrease was found in the scores of sneezing, nasal discharge, postnasal drainage, coughing after treatment (p=0.0001). During objective evaluation of nasal obstruction with acoustic rhinometry, no statistically significant difference was found between pre- and post-treatment findings. CONCLUSION: Endonasal phototherapy is an effective modality in the treatment of symptomatology in allergic rhinitis patients refractory to antiallergic drugs. It is detected that endonasal phototherapy has positive effects on the quality of life. However, no effect on nasal obstruction was found with acoustic rhinometry which is an objective method.

Evaluation of the effect of dexamethasone in experimentally induced endolymphatic hydrops in guinea pigs.

PURPOSE: The aim of this study was to investigate the audiological and histopathologic effects of dexamethasone in the treatment of experimentally induced endolymphatic hydrops. MATERIALS AND METHODS: Thirty mature, male guinea pigs weighing 400 +/- 50 g were operated on to induce experimental endolymphatic hydrops in their right ear. Left ear served as control. Subjects were separated into control and dexamethasone groups, with the latter receiving dexamethasone 5 mg/(kg d) intraperitoneally for 10 days. Electrocochleography and auditory brainstem response were applied to all subjects at preoperation, on the second postoperative day and also on the 15th postoperative day in animals that lived for a long time. The histopathologic examination of the inner ear in all animals was done at the end of the study. RESULTS: The summating potential and the ratio of the summating potential to the action potential measured on the second postoperative day were found to be increased in both groups, but more significantly in the control one. When the left and right ears were compared, significant difference was found in the control group; however, no significant difference was found between the ears in the dexamethasone group. Histopathologic examination revealed varying degrees of hydrops in the control group, but showed only normal findings or minor changes in the dexamethasone group. CONCLUSIONS: Dexamethasone can prevent the audiological and histopathologic findings of experimentally induced endolymphatic hydrops. However, these results must be supported by clinical and experimental studies designed with a large number of subjects.