Improvement of neuronal and cognitive functions following treatment with 3',4' dihydroxyflavonol in experimental focal cerebral ischemia-reperfusion injury in rats.

INTRODUCTION: Ischemia/reperfusion is a pathological condition by the restoration of perfusion and oxygenation following a period of restricted blood flow to an organ. To address existing uncertainty in the literature regarding the effects of 3', 4'-dihydroxy flavonol (DiOHF) on cerebral ischemia/reperfusion injury, our study aims to investigate the impact of DiOHF on neurological parameters, apoptosis (Caspase-3), aquaporin 4 (AQP4), and interleukin-10 (IL-10) levels in an experimental rat model of brain ischemia-reperfusion injury. MATERIALS/METHODS: A total of 28 Wistar-albino male rats were used in this study. Experimental groups were formed as 1-Control, 2-Sham, 3-Ischemia-reperfusion, 4-Ischemia-reperfusion + DiOHF (10 mg/kg). The animals were anaesthetized, and the carotid arteries were ligated (ischemia) for 30 min, followed by reperfusion for 30 min. Following reperfusion, DiOHF was administered intraperitoneally to the animals at a dose of 10 mg/kg for 1 week. During the one-week period neurological scores and new object recognition tests were performed. Then, caspase 3 and AQP4 levels were determined by PCR method and IL-10 by ELISA method in hippocampus tissue samples taken from animals sacrificed under anaesthesia. RESULTS: Brain ischemia reperfusion significantly increased both caspase 3 and AQP4 values in the hippocampus tissue, while decreasing IL-10 levels. However, 1-week DiOHF supplementation significantly suppressed increased caspase 3 and AQP4 levels and increased IL-10 values. While I/R also increased neurological score values, it suppressed the ability to recognize new objects, and the administered treatment effectively ameliorated the adverse effects observed, resulting in a positive outcome. CONCLUSIONS: The results of the study show that brain ischemia caused by bilateral carotid occlusion in rats and subsequent reperfusion causes tissue damage, but 1-week DiOHF application has a healing effect on both hippocampus tissue and neurological parameters.

Effect of 2-Week Naringin Supplementation on Neurogenesis and BDNF Levels in Ischemia-Reperfusion Model of Rats.

BACKGROUND: Ischemic stroke is the leading cause of mortality and disability worldwide with more than half of survivors living with serious neurological sequelae; thus, it has recently attracted a lot of attention in the field of medical study. PURPOSE: The aim of this study was to determine the effect of naringin supplementation on neurogenesis and brain-derived neurotrophic factor (BDNF) levels in the brain in experimental brain ischemia-reperfusion. STUDY DESIGN: The research was carried out on 40 male Wistar-type rats (10-12 weeks old) obtained from the Experimental Animals Research and Application Center of Selçuk University. Experimental groups were as follows: (1) Control group, (2) Sham group, (3) Brain ischemia-reperfusion group, (4) Brain ischemia-reperfusion + vehicle group (administered for 14 days), and (5) Brain ischemia-reperfusion + Naringin group (100 mg/kg/day administered for 14 days). METHODS: In the ischemia-reperfusion groups, global ischemia was performed in the brain by ligation of the right and left carotid arteries for 30 min. Naringin was administered to experimental animals by intragastric route for 14 days following reperfusion. The training phase of the rotarod test was started 4 days before ischemia-reperfusion, and the test phase together with neurological scoring was performed the day before and 1, 7, and 14 days after the operation. At the end of the experiment, animals were sacrificed, and then hippocampus and frontal cortex tissues were taken from the brain. Double cortin marker (DCX), neuronal nuclear antigen marker (NeuN), and BDNF were evaluated in hippocampus and frontal cortex tissues by Real-Time qPCR analysis and immunohistochemistry methods. RESULTS: While ischemia-reperfusion increased the neurological score values, DCX, NeuN, and BDNF levels decreased significantly after ischemia in the hippocampus and frontal cortex tissues. However, naringin supplementation restored the deterioration to a certain extent. CONCLUSION: The results of the study show that 2 weeks of naringin supplementation may have protective effects on impaired neurogenesis and BDNF levels after brain ischemia and reperfusion in rats.

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 impact of flavonoids and BDNF on neurogenic process in various physiological/pathological conditions including ischemic insults: a narrative review.

OBJECTIVE: Ischemic stroke is the leading cause of mortality and disability worldwide with more than half of survivors living with serious neurological sequelae thus, it has recently attracted considerable attention in the field of medical research. Neurogenesis is the process of formation of new neurons in the brain, including the human brain, from neural stem/progenitor cells [NS/PCs] which reside in neurogenic niches that contain the necessary substances for NS/PC proliferation, differentiation, migration, and maturation into functioning neurons which can integrate into a pre-existing neural network.Neurogenesis can be modulated by many exogenous and endogenous factors, pathological conditions. Both brain-derived neurotrophic factor, and flavonoids can modulate the neurogenic process in physiological conditions and after various pathological conditions including ischemic insults. AIMS: This review aims to discuss neurogenesis after ischemic insults and to determine the role of flavonoids and BDNF on neurogenesis under physiological and pathological conditions with a concentration on ischemic insults to the brain in particular. METHOD: Relevant articles assessing the impact of flavonoids and BDNF on neurogenic processes in various physiological/pathological conditions including ischemic insults within the timeline of 1965 until 2023 were searched using the PubMed database. CONCLUSIONS: The selected studies have shown that ischemic insults to the brain induce NS/PC proliferation, differentiation, migration, and maturation into functioning neurons integrating into a pre-existing neural network. Flavonoids and BDNF can modulate neurogenesis in the brain in various physiological/pathological conditions including ischemic insults. In conclusion, flavonoids and BDNF may be involved in post-ischemic brain repair processes through enhancing endogenous neurogenesis.

Naringenin Prevents Renal Injury in Experimental Hyperuricemia Through Suppressing Xanthine Oxidase, Inflammation, Apoptotic Pathway, DNA Damage, and Activating Antioxidant System.

Background/Purpose: This research was performed to determine the effect of naringenin (NAR) in experimental hyperuricemia (HU) induced by potassium oxonate (PO) on uric acid levels and xanthine oxidase (XO), inflammation, apoptotic pathway, DNA damage, and antioxidant system in kidney tissue. Study Design: Wistar Albino rats were categorized into four groups: (1) Control group, (2) PO group, (3) [PO+NAR] (2 weeks) group, and (4) PO (2 weeks)+NAR (2 weeks) group. Methods: The first group was not administered any drug. In group 2, PO was administered intraperitoneally 250 mg/kg/day for 2 weeks. In the third group, 100 mg/kg/day NAR was given intraperitoneally 1 hr after PO injection for 2 weeks. In the fourth group, PO was injected for the first 2 weeks, followed by NAR injection for the second 2 weeks. Serum uric acid levels, XO, nuclear factor-kappa B, tumor necrosis factor-alpha, interleukin-17, cytochrome c, 8-Hydroxydeoxyguanosine (8-OHdG), glutathione peroxidase (GPx), and caspase-3 levels in kidney were determined. Results: HU increased the levels of inflammatory and apoptotic parameters, XO, and 8-OHdG levels in kidney. Administration of NAR caused a decrease in these values and an increase in GPx levels. Conclusions: The results of the study show that NAR treatment reduces serum uric acid levels, and apoptosis, inflammation, and DNA damage; increases antioxidant activity in kidney in experimental HU.

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.

Irisin and Energy Metabolism and the Role of Irisin on Metabolic Syndrome.

Irisin is a thermogenic hormone that leads to causes energy expenditure by increasing brown adipose tissue (BAT). This protein hormone that enables the conversion of white adipose tissue (WAT) to BAT is the irisin protein. This causes energy expenditure during conversion. WAT stores triglycerides and fatty acids and contains very few mitochondria. They also involve in the development of insulin resistance (IR). WAT, which contains a very small amount of mitochondria, contributes to the formation of IR by storing triglycerides and fatty acids. WAT functions as endocrine tissue in the body, synthesizing various molecules such as leptin, ghrelin, NUCB2/nesfatin-1, and irisin along with fat storage. BAT is quite effective in energy expenditure, unlike WAT. The number of mitochondria and lipid droplets composed of multicellular cells in BAT is much higher when compared to WAT. BAT contains a protein called uncoupling protein-1 (UCP1) in the mitochondrial membranes. This protein pumps protons from the intermembrane space toward the mitochondrial matrix. When UCP1 is activated, heat dissipation occurs while ATP synthesis does not occur, because UCP1 is a division protein. At the same time, BAT regulates body temperature in infants. Its effectiveness in adults became clear after the discovery of irisin. The molecular mechanism of exercise, which increases calorie expenditure, became clear with the discovery of irisin. Thus, the isolation of irisin led to the clarification of metabolic events and fat metabolism. In this review, literature information will be given on the effect of irisin hormone on energy metabolism and metabolic syndrome (MetS).

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.

Effects of putrescine on oxidative stress, spermidine/spermine-N(1)-acetyltransferase, inflammation and energy levels in liver and serum in rats with brain ischemia-reperfusion.

We aimed to examine the effects of brain ischemia-reperfusion (IR) especially on serum parameters or liver enzymes, free radicals, cytokines, oxidatively damaged DNA, spermidine/spermine N-1-acetyltransferase (SSAT). The effects of addition of putrescine on IR will be evaluated in terms of inflammation and oxidant-antioxidant balance in liver.The study was conducted on 46 male Albino Wistar rats weighing 200-250 g. The rats were grouped into: 1-Sham group (n = 6). 2-IR group (n = 8): The carotid arteries were ligated for 30-min and reperfusion was achieved for 30-min under general anesthesia. 3-Ischemia + putrescine + reperfusion group (IPR) (n = 8): Unlike the IR group, a single dose of 250 µmol kg-1 putrescine was given by gavage at the beginning of reperfusion. In putrescine treatment groups in addition to the procedures performed in the IR group a total of 4 doses of 250 µmol kg-1 putrescine were given at 12-h intervals, with the first dose immediately after 30-min reperfusion (4-IR+putrescine group (IR+P1) (n = 8)); 3 h after the 30-min reperfusion (5-IR+putrescine group (IR+P2) (n = 8)); 6 h after the 30-min reperfusion (6-IR+putrescine group (IR+P3) (n = 8)). ALT, AST, ATP, NO, SSAT, 8-OHdG levels were analyzed in the serum, and liver samples. NF-κB and IL-6 levels were analyzed in the liver samples.Brain IR causes inflammatory, oxidative and DNA damage in the liver, and putrescine supplementation through gavage reduces liver damage by showing anti-inflammatory and antioxidant effects.

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.

Role of exogenous putrescine in the status of energy, DNA damage, inflammation, and spermidine/spermine-n(1)- acetyltransferase in brain ischemia-reperfusion in rats.

Objectives: This study aims to investigate the role of putrescine against brain ischemia-reperfusion (IR) injured rats administered with 250 µmol/kg exogenous putrescine and highlight the IR-associated mechanisms in energy metabolism and inflammatory pathway. Materials and Methods: The rats were divided into six groups: 1-Sham group; 2-IR group, 30 min of ischemia and 30 min of reperfusion was performed with bilateral carotid occlusion (BCAO); 3-IPR group, a single oral dose of putrescine was administered at the start of the 30-minute reperfusion; while in the other treatment groups, 4 doses of putrescine were given within 12-hour intervals. After 30 min of reperfusion, the first dose was administered immediately in the IR-PI (group 4), after 3 hr in IR-PII (group 5), and after 6 hr in IR-PIII (group 6). Interleukin-6 (IL-6), Nuclear factor NF-kappa-B (NF-kB), Adenosine triphosphate (ATP), total Nitric oxide (NO), 8-hydroxyguanosine (8-OHdG), Spermidine/Spermin N-acetyltransferase (SSAT) levels were analyzed in brain tissues. Results: IR reduced brain ATP levels; however, putrescine treatment reversed this state. Brain NO and 8-OHdG levels, and NF-kB and IL-6 levels increased significantly in the IR group and these elevations were decreased in putrescine administered groups. SSAT levels were higher in the IR-PII group. The lowest levels were observed in the IR-PIII group. Conclusion: The exogenous putrescine supplementation after cerebral IR creates neuroprotective effects independent of the time of administration; according to conditions such as formation of radicals in the brain, the spread of the inflammation and the need for consumption of energy are considered as a whole.

Naringenin Prevents Inflammation, Apoptosis, and DNA Damage in Potassium Oxonate-Induced Hyperuricemia in Rat Liver Tissue: Roles of Cytochrome C, NF-κB, Caspase-3, and 8-Hydroxydeoxyguanosine.

Background: Hyperuricemia (HU) is a metabolic disease characterized by high uric acid levels in the blood. HU is a risk factor for diabetes, cardiovascular complications, metabolic syndrome, and chronic kidney disease. Purpose: The present study was performed to determine the effect of experimental HU on xanthine oxidase (XO), tumor necrosis factor-alpha (TNF-α), nuclear factor-kappa B (NF-κB), interleukin-17 (IL-17), cytochrome C, glutathione peroxidase (GPx), caspase-3, and 8-hydroxydeoxyguanosine (8-OHdG) levels in liver tissues of rats. Study Design: Thirty-five, male, Wistar albino-type rats were used for this study. Experimental groups were formed as follows: Group 1: control group; Group 2: potassium oxonate (PO) group; group 3: PO+NAR (naringenin; 2 weeks) group; and Group 4: PO (2 weeks)+NAR (2 weeks) group (total of 4 weeks). Methods: The first group was not given anything other than normal rat food and drinking water. In the second group, a 250 mg/kg intraperitoneal dose of PO was administered for 2 weeks. In the third group, 250 mg/kg intraperitoneal PO (application for 2 weeks) and 100 mg/kg NAR intraperitoneally 1 hr after each application were administered. In the fourth group, intraperitoneal PO administration was applied for 2 weeks, followed by intraperitoneal administration of NAR for 2 weeks (4 weeks in total). At the end of the experimental period, XO, TNF-α, NF-κB, IL-17, cytochrome C, GPx, caspase-3, and 8-OHdG levels were determined in liver tissues. Results: HU increased XO, TNF-α, NF-κB, IL-17, cytochrome C, caspase-3, and 8-OHdG levels in liver tissues. However, both 2 and 4 weeks of NAR supplementation decreased these values, and also NAR supplementation led to an increase in GPx levels in tissues. Conclusions: The results of the study show that increased inflammation, apoptosis, and DNA damage in experimental HU can be prevented by administration of NAR due to inhibition of cytochrome C, NF-κB, caspase-3, and 8-OHdG.

Chronic Running Exercise Regulates Cytotoxic Cell Functions and Zinc Transporter SLC39A10/ZIP10 Levels in Diabetic Rats.

The aim of this study is to investigate how chronic running exercise affects ZIP10 levels in thymus and spleen tissue as well as immune parameters in diabetic rats. A total of 40 adult male Wistar rats were divided into 4 equal groups: group 1, control; group 2, exercise control; group 3, diabetes; group 4, diabetes + exercise. Diabetes was induced by injecting intraperitoneal streptozotocin (STZ) at a dose of 40 mg/kg twice with 24-h intervals to the animals in groups 3 and 4. The animals in group 2 and group 4 underwent exercise for 45 min on the rat treadmill for 4 weeks at 20 m/min. Twenty-four hours after the last running exercise, the animals were sacrificed under general anesthesia. Immunological parameters were determined by flow cytometric method; tissue ZIP 10 levels were determined by ELISA method. The diabetic group had the lowest natural killer (NK) and natural killer T (NKT) cells percentages. Chronic exercise partially improved NK and NKT cell percentages in diabetic rats. The diabetic group had the lowest ZIP10 levels in spleen and thymus tissue. ZIP10 values in spleen and thymus tissue of diabetes exercise group were significantly higher than diabetes group. The results of our study show that the impaired cytotoxic cell functions in diabetes are partially corrected with 4 weeks of chronic exercise, and that the suppressed ZIP 10 levels in diabetic rats are reversed by 4 weeks of chronic exercise.

3',4'-Dihydroxyflavonol (DiOHF) prevents DNA damage, lipid peroxidation and inflammation in ovarian ischaemia-reperfusion injury of rats.

This study aimed to determine the effect of 3',4'-Dihydroxyflavonol (DiOHF) on lipid peroxidation, DNA damage and inflammation in ovarian ischaemia (I)-reperfusion (R) injury. This study was performed on 44 Wistar-albino female rats. Groups were designed as Control; Sham; I/R (the left ovary was ligated for 2 h and then reperfused for 2 h); I/R + DiOHF (after 2 h ischaemia and 2 h reperfusion, 30 mg/kg of DiOHF was given intraperitoneally and reperfusion was allowed for 2 h more); I + DiOHF + R (after 2 h I, 30 mg/kg of DiOHF was given at the beginning of 2 h reperfusion); DiOHF + I/R (2 h after DiOHF administration, the left ovary was ligated for 2 h and then reperfused for 2 h). Blood and ovarian tissue samples were analysed for GSH, MDA, 8-OHdG, SOD, and IL-6. Ovarian tissue was examined histopathologically. Ovarian I/R has led to inflammation and oxidative damage. However, DiOHF activated the antioxidant system and prevented DNA damage induced by I/R in ovarian tissue. Vascularisation, oedema, and inflammation also occurred in ovarian tissue in I/R group. The results of this study indicated that I/R led to disturbance of the oxidant/antioxidant system balance and increased DNA damage; however, DiOHF supplementation prevented DNA damage, lipid peroxidation and inflammation by increasing the antioxidant system in ovarian I/R injury in rats. However, in potential I/R situations, DiOHF application appears to be beneficial in reducing inflammation, oxidant injury, and DNA damage, and in activating the antioxidant system. IMPACT STATEMENTWhat is already known on this subject? Ischaemia/reperfusion (I/R) injuries lead to damage in cells or tissues due to insufficient blood flow.What do the results of this study add? Increased DNA injury and inflammatory response (IL-6) and structural impairment were treated by administration of intraperitoneal (DiOHF) which strongly stimulated the antioxidant system, inhibited antioxidant activities, prevented DNA damage and inflammation process.What are the implications of these findings for clinical practice and/or further research? This study's strength is that it is the first research demonstrates the prevention of DNA damage in ovarian I/R by DiOHF supplementation. This flavonoid (DiOHF) may be used for treatment in different ovarian ischaemia/reperfusion.

Learning, Neurogenesis and Effects of Flavonoids on Learning.

Learning and memory are two of our mind's most magical abilities. Different brain regions have roles to process and store different types of memories. The hippocampus is the part of the brain responsible for receiving information and storing it in the neocortex. One of the most impressive characteristics of the hippocampus is its capacity for neurogenesis which is a process, new neurons are produced and then transformed into mature neurons and integrated into neural circuits. The neurogenesis process in the hippocampus, an example of neuroplasticity in the adult brain, is believed to aid hippocampal-dependent learning and memory. New neurons are constantly produced in the hippocampus and integrated into the pre-existing neuronal network, this allows old memories already stored in the neocortex to be removed from the hippocampus and replaced with new ones. Factors affecting neurogenesis in the hippocampus may also affect hippocampal-dependent learning and memory. The flavonoids can exert particularly powerful actions in mammalian cognition and improve hippocampaldependent learning and memory by positively affecting hippocampal neurogenesis.

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.

The effects of thyroid dysfunction on DNA damage and apoptosis in liver and heart tissues of rats.

OBJECTIVES: Thyroid hormones affect many enzymes, organs, and systems. They also play a role in complex biological events including development and growth. The main objective of this study was to analyze the effects of thyroid dysfunction on DNA damage and apoptosis in liver and heart tissues as well as the treatment of these disorders. METHODS: Thirty-eight Wistar-albino male rats were randomly divided into five groups: 1. Control group (n=6): The rats were sacrificed without any application and liver and heart samples were collected. 2. Hypothyroidism group (n=8): Prophyltiouracil (PTU)-10 mg/kg/day was applied to induce hypothyroidism by intraperitoneal route for two weeks. 3. Hypothyroidism + Thyroxine group (n=8): After one week of PTU application (10 mg/kg/day), a high dose of l-thyroxine (1.5 mg/kg/day) was applied by intraperitoneal route for one week. 4. Hyperthyroidism group (n=8): l-thyroxine (0.3 mg/kg/day) was applied intraperitoneally to induce hyperthyroidism for two weeks. 5. Hyperthyroidism + PTU group (n=8): After one week of high dose l-thyroxine application, PTU (10 mg/kg/day) was applied for one week. RESULTS: Liver and heart tissues were collected to evaluate 8-hydroxy-2 deoxyguanosine (8-OHdG), caspase-8 and caspase-9 levels. Hypothyroidism caused DNA damage in the liver, while hyperthyroidism caused DNA damage in the heart tissue. Hyperthyroidism also led to a significant increase in levels of caspase-8 and caspase-9 in liver tissue. CONCLUSIONS: The results of the study show that DNA damage and caspase levels in the heart and liver are affected differently in experimental hypothyroidism and hyperthyroidism.

Increased apoptosis, tumor necrosis factor-α, and DNA damage attenuated by 3',4'-dihydroxyflavonol in rats with brain Ischemia-reperfusion.

OBJECTIVES: This research was aimed to find out the effects of 3',4'-dihydroxyflavonol (DiOHF) on apoptosis, DNA damage, and tumor necrosis factor-α (TNF-α) levels in the frontal cortex of rats with induced experimental brain ischemi reperfusion. MATERIALS AND METHODS: A total of 38 Wistar albino male rats were used. Groups were created as 1-Sham; 2-Ischemia-reperfusion (I/R); 3-I/R + DiOHF (10 mg/kg); 4-Ischemia + DiOHF + reperfusion; 5-DiOHF + I/R. I/R was performed by carotid artery ligation for 30 min in anesthesized animals. Following experimental applications, blood samples were taken from anesthetized rats to obtain erythrocyte and plasma. Later, the rats were killed by cervical dislocation, and frontal cortex samples were taken and stored at - 80oC for the analysis. RESULTS: In the ischemic frontal cortex tissue sections degenerate neuron numbers, Terminal deoxynucleotidyl transferase-dUTP nick end labeling (TUNEL) positive cell ratio and caspase-3 positive cell ratio increased. Malondialdehyde, TNF-α, and 8-OHdG levels were increased in both plasma and tissue in ischemia group, whereas tissue and erythrocyte glutathione levels were significantly suppressed. However, these values were significantly reversed by DiOHF treatment. CONCLUSION: The results of the study showed that I/R significantly increased apoptosis, TNF-α, and DNA damage in rats with brain I/R. However, 10 mg/kg intraperitoneal DiOHF treatment improved deterioted parameters.

Zinc is a strong stimulant of metallothionein synthesis in the ischaemic testis tissue.

This study was performed to determine the effect of zinc supplementation effects on metallothionein levels in testis ischaemia-reperfusion of rats. The experimental groups were designed as Control, Sham, Ischaemia-Reperfusion (I/R) and I/R + Zinc supplemented. Zinc supplemented as 5 mg/kg day for 3 weeks. Testis tissues were analysed for metallothionein by immunohistochemical staining procedures. Group comparison showed that the zinc-supplemented ischaemia-reperfusion group had a significantly higher level of cells strongly stained with metallothionein than all other groups. A general evaluation of the results suggests that zinc supplementation is a strong stimulant of metallothionein synthesis in the ischaemic testis tissue.