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.

Melatonin protects retinal tissue damage in streptozotocin-induced aged rats.

OBJECTIVES: The aim of this study was to investigate how melatonin administration affects retinal oxidative damage and retinal SIRT1 gene activation in diabetic elderly female rat model. METHODS: 16-months-old female rats were used in the study. A total of 24 rats were divided into 4 groups in equal numbers: Group 1. Control, Group 2. Control + Melatonin, Group 3. Diabetes, Group 4. Diabetes + Melatonin. In group 3 and 4 rats, diabetes was induced by intraperitoneal (IP) injection of streptozotocin. Groups 2 and 4 were given ip melatonin for 4 weeks. SIRT-1 gene expression was determined by PCR method and GSH and MDA levels by ELISA in retinal tissue samples taken from animals sacrificed under general anesthesia. RESULTS: In our study, the highest retinal SIRT1 expression values were obtained in the diabetes + melatonin (G4) group. The retinal SIRT1 expression values of the diabetes group (G3) were lower than group 4 and higher than the general control (G1) and control + melatonin (G2) groups. Again in our study, the highest retinal MDA values were obtained in the diabetes group (G3). The highest retinal GSH values were obtained in the Diabetes + melatonin group (G4). CONCLUSION: The results of our study showed that melatonin supplementation has a protective effect on retinal tissue in a diabetic elderly female rat model. This protective effect of melatonin supplementation occurs by increasing both retinal antioxidant activity and retinal SIRT1 gene expression.

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 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.

Melatonin has a protective effect against lipid peroxidation in the bone tissue of diabetic rats subjected to acute swimming exercise.

Aim The present study aimed to examine the effects of melatonin supplementation on lipid peroxidation in the bone tissue of diabetic rats subjected to acute swimming exercise. Methods The study was conducted on 80 Sprague-Dawley type adult male rats which were equally allocated to eight groups: group 1, general control; group 2, melatonin-supplemented control; group 3, melatonin-supplemented diabetic control; group 4, swimming control; group 5, melatonin-supplemented swimming; group 6, melatonin-supplemented diabetic swimming; group 7, diabetic swimming; group 8, diabetic control. In order to induce diabetes, the animals were subcutaneously injected with 40 mg/kg streptozotocin (STZ). The animals were supplemented with 3 mg/kg/day melatonin intraperitoneally (IP) for 4 weeks. At the end of the study, the animals were decapitated to collect bone tissue samples which were examined to find out the malondialdehyde (MDA) (nmol/g/protein) and glutathione (GSH) (mg/dL/g protein) levels. Results The highest MDA values in the bone tissue were found in groups 7 and 8. MDA levels in the bone tissue in groups 3 and 6 were lower than the levels in groups 7 and 8, but higher than those in all other groups. Groups 3, 5 and 6 had the highest bone tissue GSH values. On the other hand, the lowest GSH level was established in groups 7 and 8. Conclusion The results of the present study indicated that the cell damage caused by acute swimming exercise and diabetes in the bone tissue could be prevented by melatonin supplementation.

The effect of zinc and melatonin supplementation on immunity parameters in breast cancer induced by DMBA in rats.

OBJECTIVE: The aim of the study was to determine the effects of zinc and melatonin supplements on the immunity parameters of female rats with breast cancer induced by DMBA. METHODS: Group 1; Control, Group 2; 7,12-dimethylbenz[a]anthracene (DMBA), Group 3; DMBA + zinc, Group 4; DMBA + melatonin, Group 5; DMBA + zinc + melatonin. The rats' breast cancer was induced by DMBA 80 mg/kg. Groups 3-5 received daily 5 mg/kg doses of zinc, melatonin, and zinc + melatonin, respectively. Lymphocyte rates, T-lymphocyte subgroups, B-lymphocyte and natural killer cells (NK), and natural killer T (NKT) were evaluated. RESULTS: The most significant increase in lymphocyte, T-lymphocyte, and CD4 lymphocyte rates was found in Group 5. The highest NKT cell rates were found in Group 3. CONCLUSIONS: Findings show that zinc and melatonin supplements have led to an increase in the immunity parameters of rats with breast cancer.