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. AIM: 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.

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.

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.

Molecular Mechanisms of Early and Late LTP.

LTP is the most intensively studied cellular model of the memory and generally divided at least two distinct phases as early and late. E-LTP requires activation of CaMKII that initiates biochemical events and trafficking of proteins, which eventually potentiate synaptic transmission, and is independent of de novo protein synthesis. In contrast, L-LTP requires gene expression and local protein synthesis regulated via TrkB receptor- and functional prions CPEB2-3-mediated translation. Maintenance of LTP for longer periods depends on constitutively active PKMζ. Throughout this review, current knowledge about early and late phases of LTP will be reviewed.

Effect of resveratrol administration on muscle glycogen levels in rats subjected to acute swimming exercise.

The present study aims to examine how resveratrol administration affects muscle glycogen levels in rats subjected to an acute swimming exercise bout. The study was conducted on adult male rats of Wistar-Albino. The 28 rats used in the study were equally divided among four groups: Group 1, Control Group: The group fed on a standard diet and not subjected to any procedure. Group 2, Control Swimming Group: The group fed on a standard diet and subjected to an acute swimming exercise bout for 30 minutes at the end of the study. Group 3, Resveratrol Group: The group fed on a standard diet and given (10 mg/kg) resveratrol in drinking water for four weeks. Group 4, Resveratrol + Swimming Group: The group fed on a standard diet, given (10 mg/kg) resveratrol in drinking water for four weeks and subjected to a 30-minute acute swimming exercise at the end of the study. At the end of the four weeks, the animals were decapitated, muscle glycogen levels using immunohistochemical method. The highest muscle glycogen levels were obtained in the resveratrol-administered Group 3 and the lowest levels in group 2 (swimming group) (p<0.05). The results of the study demonstrate that resveratrol support had a protective and/or regulatory effect on mucle glycogen in both exercised and not-exercised rats.

Resveratrol does not affect leptin while it has regulatory effects on liver glycogen levels in exercised and non-exercised rats.

Resveratrol (RES) is a well-known phytocompound and food component which has antioxidative and multifunctional bioactivities. The present study aims to examine how resveratrol administration affects plasma leptin and liver glycogen levels in rats subjected to an acute swimming exercise bout. The study was carried out on Wistar-Albino type adult male rats, each group include 7 rats. Group 1, Control Group. Group 2, Control Swimming Group: The group fed on a standard diet and subjected to an acute swimming exercise bout for 30 minutes at the end of the study. Group 3, Resveratrol Group: The group fed on a standard diet and given (10 mg/kg) resveratrol in drinking water for four weeks. Group 4, Resveratrol + Swimming Group: The group fed on a standard diet, given (10 mg/kg) resveratrol in drinking water for four weeks and subjected to a 30-minute acute swimming exercise at the end of the study. Plasma leptin levels using ELISA method (ng/l) and liver glycogen levels were determined by using histochemical method (number/0.1 mm2). Four weeks resveratrol administration to exercised and not-exercised rats did not cause a change in plasma leptin levels. Liver glycogen levels were 17.00 ± 3.16; 14.12 ± 2.98; 20.82 ± 1.97; 16.38 ± 1.27 (mean ± sd); respectively in groups 1, 2, 3, 4. Resveratrol administration to rats subjected to a bout of acute swimming exercise produced an effect that prevented the decrease in liver glycogen (p < 0.05). The study highlights that resveratrol supplementation may have regulatory effects on liver glycogen levels in exercised and non-exercised rats.

Review: The role of zinc in the endocrine system.

Zinc is essential in the regulation of a variety of physiological and biochemical events in the organism. It plays a critical role in maintaining the cell membrane integrity, protein-carbohydrate-lipid metabolism, immune system, wound injury and in the regulation of a number of other biological processes associated with normal growth and development. Physiological and biochemical levels of many hormones are affected by zinc metabolism. Therefore, growth impairment, hypogonadism, and some endocrine diseases are associated with the deficiency of zinc. These effects of zinc are considered versatile. Zinc increases the synthesis of the growth hormone and its number of receptors; thus, it is an important mediator in the binding of this hormone to its receptor. Found in a large quantity in the pancreas tissue, zinc has a part in the regulation of the effect of insulin. Zinc is involved to much more thyroid hormone metabolism such as hormone synthesis, receptor activity, conversion of T4 to T3, and production of carrier proteins. The low levels of zinc and high levels of leptin in obese individuals point to a critical relationship between zinc and leptin. Zinc is related to enzyme activity to melatonin synthesis. Melatonin has regulatory activity for zinc absorption from gastrointestinal system. Zinc particularly affects the conversion of testosterone to dihydrotestosterone, as 5α-reductase that is involved in this conversion is a zinc-dependent enzyme. In consideration of these relations, zinc is accepted to play critical roles in the endocrine system. The aim of the current review is to draw attention to the effects of zinc on the endocrine system.

Effect of 3'-4'-dihydroxyflavonol on lipid per oxidation in experimental renal ischemia-reperfusion in rats.

This study aimed to examine the affects of 3'-4'-dihydroxyflavonol (DiOHF) on lipid peroxidation in experimental renal ischemia-reperfusion. The research was conducted on Wistar-albino type male rat. The experimental groups were formed as 1.Control; 2.Sham; 3.Ischemia; 4.Ischemia+reperfusion; 5.DiOHF+Ischemia; 6.Ischemia+ DiOHF + reperfusion. The highest tissue glutathione levels were found in groups 5 and 6. Groups 1 and 2, which were control and sham groups respectively, had the lowest tissue GSH values. Ischemia group was found to have the highest tissue malondialdehyde (MDA) level. Tissue MDA levels in group 4 were lower than those in group 3, however, higher than the levels in all other groups. Erythrocyte GSH levels in groups 5 and 6 were higher than the levels in all other groups. Group 4 has highest plasma MDA values. Plasma MDA levels in group 3 were lower than the levels in Group 4, but higher than those in other groups. The results of the study indicate that intraperitoneal DiOHF administration inhibits lipid per oxidation that intensifies in the case of renal ischemia-reperfusion injury in rats.

The effects of zinc and melatonin on muscle ischaemi-reperfusion injury in rat.

Ischemia-reperfusion leads to damage in cell or tissue due to insufficient blood flow. The aim of present study was to determine the effect of zinc, melatonin and zinc + melatonin supplementations during 3 weeks on muscle tissue and plasma MDA and GSH levels. This study was performed on 38 male Wistar-Albino rats. Experiments groups were designed as sham-control, ischemia-reperfusion (I/R), zinc + I/R, melatonin + I/R and zinc + melatonin + I/R Ischemia-reperfusion was induced by left femoral artery occlusion (1 hour) and reopening (1 hour).  At the end of experiments tissue and blood samples were analysed for MDA and GSH. MDA levels were increased, GSH levels decreased in I/R groups. However, zinc and melatonin supplementation inhibited  MDA and increased GSH levels in I/R groups. The results of present study show that increased lipid peroxidation in muscle tissue by ischemia-reperfusion may be prevented by zinc and melatonin or zinc plus melatonin supplementation.

3',4'-Dihydroxyflavonol attenuates spatial learning and memory impairments in global cerebral ischemia.

OBJECTIVES: In the present study, effects of 3',4'-dihydroxyflavonol (DiOHF) on anxiety-like behavior, and learning and memory were investigated in a model of transient global cerebral ischemia and reperfusion. METHODS: The animals were assigned to sham-operated, ischemia, and two DiOHF-treated (10 mg/kg i.p.) groups. DiOHF was administered at 1 hour before and immediately after the ischemia. Male rats were subjected to bilateral common carotid artery occlusion to induce acute cerebral ischemia for 20 minutes, followed by reperfusion for 7 days. The openfield, elevated plus maze (EPM), and Morris water maze tests were used to evaluate the effects of DiOHF treatment on ischemia-induced locomotor activity, anxiety-like behavior, and spatial and recognition memory impairments, respectively. RESULTS: In the open field test, locomotor activity in the ischemic rats was not altered 6 days after the ischemia, nor was anxiety-like behavior, which was evaluated with the EPM (P > 0.05). In the water-maze test, cerebral ischemia significantly decreased the exploration time in the target quadrant, and the platform crossing counts were lower (P < 0.05) in the probe trial test; this memory impairment was significantly improved by DiOHF applied 1 hour before and immediately after ischemia (P < 0.05). DISCUSSION: All together, these findings suggest that DiOHF reverses spatial learning and memory deficits resulting from transient global ischemia but has no significant effect on anxiety-like behavior.

Leptin, NPY, Melatonin and Zinc Levels in Experimental Hypothyroidism and Hyperthyroidism: The Relation to Zinc.

Since zinc mediates the effects of many hormones or is found in the structure of numerous hormone receptors, zinc deficiency leads to various functional impairments in the hormone balance. And also thyroid hormones have important activity on metabolism and feeding. NPY and leptin are affective on food intake and regulation of appetite. The present study is conducted to determine how zinc supplementation and deficiency affect thyroid hormones (free and total T3 and T4), melatonin, leptin, and NPY levels in thyroid dysfunction in rats. The experiment groups in the study were formed as follows: Control (C); Hypothyroidism (PTU); Hypothyroidism+Zinc (PTU+Zn); Hypothyroidism+Zinc deficient; Hyperthyroidism (H); Hyperthyroidism+Zinc (H+Zn); and Hyperthyroidism+Zinc deficient. Thyroid hormone parameters (FT3, FT4, TT3, and TT4) were found to be reduced in hypothyroidism groups and elevated in the hyperthyroidism groups. Melatonin values increased in hyperthyroidism and decreased in hypothyroidism. Leptin and NPY levels both increased in hypo- and hyperthyroidism. Zinc levels, on the other hand, decreased in hypothyroidism and increased in hyperthyroidism. Zinc supplementation, particularly when thyroid function is impaired, has been demonstrated to markedly prevent these changes.

Effect of Zinc and Melatonin on Oxidative Stress and Serum Inhibin-B Levels in a Rat Testicular Torsion-Detorsion Model.

The present study was aimed to examine the effects of 3-week zinc and melatonin administration on testicular tissue injury and serum Inhibin-B levels caused by unilateral testicular torsion-detorsion in rats. The study was performed on 60 Wistar Albino-type adult male rats. The animals were allocated to 6 groups in equal numbers. 1. Control; 2. Sham; 3. Ischemia-reperfusion; 4. Zinc + ischemia-reperfusion; 5. Melatonin + ischemia-reperfusion; 6. Zinc + melatonin + ischemia-reperfusion. Zinc and melatonin were administered before ischemia-reperfusion at doses of 5 and 3 mg/kg respectively, by intraperitoneal route for a period of 3 weeks. Testicular torsion-detorsion procedures consisted of ischemia for 1 h and then reperfusion for another hour of the left testis. Blood and testicular tissue samples were collected to analyze erythrocyte and tissue GSH and plasma and tissue MDA, Inhibin-B levels. The highest erythrocyte and testis GSH values were found in zinc, melatonin, and zinc + melatonin groups (p < 0.001). Torsion-detorsion group has significantly lower erythrocyte GSH levels and higher plasma MDA values (p < 0.001). Serum inhibin-B and spermatogenic activity levels in the torsion-detorsion group were also significantly lower than those in the other groups (p < 0.001). However, zinc-, melatonin-, and melatonin + zinc-supplemented groups have higher inhibin-B and spermatogenetic activity (p < 0.001). The results of the study show that zinc, melatonin, and melatonin + zinc administration partially restores the increased oxidative stress, as well as the reduced inhibin-B and spermatogenic activity levels in testes ischemia-reperfusion in rats. Suppressed inhibin-B levels in the testicular tissue may be a marker of oxidative stress.

The Effect of Zinc Deficiency and Supplementation on Elements in the Kidney Tissue of Ovariectomized Rats: Histopathologic Changes.

The objective of the present study is to determine the effects of zinc deficiency in and zinc supplementation to ovariectomized rats on some elements in kidney tissue. The study included 40 Sprague-Dawley type adult female rats. The experimental animals were randomized into four groups with equal numbers as follows: Group 1: Control (10). Group 2: Ovariectomized control (10). Group 3: Ovariectomized + zinc supplemented (10). Group 4: Ovariectomized + zinc deficient (10). After the animals were decapitated at the end of the experiment, element levels were determined by Atomic Emission (ICP-AES) as mg/g/wet tissue for calcium, phosphate, zinc, aluminum, copper, iron, lithium, and manganese and µg/g/wet tissue for magnesium in the kidney tissue. Additionally, the tissue samples were subjected to a histopathologic assessment. An examination of the study results showed that ovariectomy significantly reduced calcium, phosphorus, and zinc levels, while zinc supplementation to the rats following ovariectomy restored the reduced element levels to normal (0.10 ± 0.03, 0.85 ± 0.16, 0.11 ± 0.03 vs 0.19 ± 0.06, 1.86 ± 0.18, 0.52 ± 0.05). Group 4, which was both ovariectomized and fed on a zinc-deficient diet, had significantly lower aluminum, copper, and lithium values. Calcification, inflammation, and sclerotic changes in group 4, the group which was fed on a zinc-deficient diet, were greater in comparison to other groups (p < 0.05). Results of the study suggest that ovariectomy + zinc deficiency leads to calcification, inflammation, and sclerotic changes in renal tissue and significantly reduces element levels, whereas zinc supplementation after ovariectomy restores the lowered element levels to normal.

The Effect of 3',4'-Dihydroxyflavonol on Lipid Peroxidation in Rats with Cerebral Ischemia Reperfusion Injury.

The aim of present study was to determine the effect of 3',4'-dihydroxyflavonol (DiOHF) on lipid peroxidation in experimental brain ischemia-reperfusion in rats. Present study was performed on the 34 male Wistar-albino rats, weigth 350-400 g. Experiment groups were designed as 1-Sham; 2-Ischemia-reperfusion; animal were anesthesized and carotid arteried were clemped for 20 min and reperfusion (7 days). 3-DiOHF + Ischemia-reperfusion; DiOHF was given to animals as 10 mg/kg by intraperitoneal. 4- Ischemia + DiOHF + Reperfusion; 5- Ischemia-reperfusion + DiOHF. Blood samples and serebral cortex were analysed for malondyaldehyde (MDA), NO (nitric oxide), xanthine oxidase (XO), glutathione (GSH) and glutathione peroxidase (GPx). Blood MDA levels were significantly higher ischemia-reperfusion groups (P < 0.005). However, DiOHF inhibited MDA. Ischemia-reperfusion led to increased XO and NO but DiOHF supplementation reduced NO and XO. DiOHF increased GSH and GPx levels compared to ischemia-reperfusion group. All together, our present study showed that intraperitoneal DiOHF supplementation has protective effect on brain ischaemia-reperfusion injury in rat.

Chronic (3-Weeks) Treatment of Estrogen (17ß-Estradiol) Enhances Working and Reference Memory in Ovariectomized Rats: Role of Acetylcholine.

Recently there has been a growing interest in the effects of estrogen on cognitive functions. In this study, we aimed to examine 17ß-estradiol treatment on working and reference memory in ovariectomized rats. We also examined the changes in the acetylcholine (ACh) levels in the brain areas associated with learning and memory. The study was performed on Sprague-Dawley type 3-month-old female rats. The rats were divided into four groups as control, ovariectomy (OVX), and OVX and estrogen treatment (10 µg/day i.p. 17ß-estradiol) groups for 3 (OVX + E3) and 21 days OVX + E21). The rats were trained on eight arm radial maze task with eight arms baited to assess spatial memory, in addition four arms baited to assess both working and reference memory performances. The electron microscope images of the ACh vesicles in the frontal cortex, temporal cortex and hippocampus areas of the brain which are important regions for learning and memory were screened. Results showed that long term 17ß-estradiol treatment has positive effects on both reference memory and working memory and that ACh vesicles increased in the examined brain areas, especially in hippocampus. Our results suggest that 3 weeks 17ß-estradiol treatment may have an ameliorative effect on the memory through the central cholinergic system.

Effect of vitamin A administration on free radicals and lactate levels in individuals exercised to exhaustion.

This study was performed to explore the effect of vitamin A administration on Free Radicals production and antioxidant system activity and lactate levels in individuals exercised to exhaustion The study registered 10 healthy sedentary males their mean age was 22,85±0,26 years. The subjects were orally administrated with 300 mg vitamin A (retinol) for 4 weeks and engaged in strenuous exercise (using the Bruce protocol) once a week. Blood samples were collected from the subjects at four different times, before and after the supplementation and before and after exercise to analyze Malondialdehyde (MDA), Nitric oxide (NO), Glutathione (GSH), Glutathione peroxidase (GSH-Px), Catalase (CAT), Superoxide dismutase (SOD) levels using colorimetric ELISA test kits and plasma lactate levels using an autoanalyzer. Exhaustion exercise leaded to an increase in both MDA, NO, and lactate, and GSH, GSH-Px, CAT and SOD levels compared to resting levels both before and after supplementation (p<0.05). Increased NO levels found in pre-supplementation exhaustion showed a significant decrease after the supplementation of vitamin A (p<0.05), but the other parameters were not changed after vitamin A administration. The results of our study demonstrate that the increase caused by 4-week strenuous exercise in the levels of the free radical NO was offset by vitamin A supplementation. It can be suggested that supplementation of vitamin A at physiological doses has a limited effect on lipid peroxidation caused by strenuous exercise.

Review - Selenium - Its metabolism and relation to exercise.

Selenium (Se), which is commonly found in nature, is one of the essential trace elements necessary for the normal development of human and animal organisms. Selenium was first defined in 1818 by the Swedish chemist Berzelius in sulfuric acid residues. At the end of 1960s, the role of selenium in human health began to attract attention and human diseases that resembled animal diseases responding to selenium was started to be investigated. Selenium, which is highly important for human health, is necessary for a variety of metabolic processes, including thyroid hormone metabolism, protection against oxidative stress and immunity functions. Selenium is a molecule that activates glutathione peroxidase, and thus, it is involved in the antioxidant mechanisms that prevent oxidant damage. Exhaustive physical exercise is known to cause oxidant damage, probably by promoting free radical production in many tissues, including muscle, liver, heart and lungs in animals. The increase in oxidative stress during exercise and recognition of selenium's stimulation of antioxidant activity inevitably suggest a relation between selenium and exercise. The present review aims to provide information on selenium metabolism and the relation between selenium and exercise.

The effect of zinc supplementation on the urinary excretion of elements in female athletes.

This study was carried out to find out how oral zinc supplementation to elite athletes affects the element changes in the urine. The study registered 10 female athletes who were on the women's volleyball team of Gazi University Sports Club and whose mean age, weight, and height were 14.2±0.42 years, 59.8±7.79kg and 173.6±6.15 cm. The study protocol was approved by the local ethics committee. The athletes who continued their daily routine training sessions (6 days/week) were supplemented with 220mg/day oral zinc sulfate for 4 weeks. In order to induce exhaustion, the subjects were put to a 20-meter shuttle run test before and after supplementation. A total, 7 times urine samples were collected follows as pre and post exercise before the start of the experiment and at the end (4 times), at the end of first, second and third week (3 times). Urinary levels of magnesium, phosphorus, and calcium (mg/dl), as well as zinc, copper, and selenium (µg/dl) were analyzed in the atomic emission device (ICP-MS). Arithmetic means and standard errors of the data were calculated. Kruskal Wallis test was used to determine differences between weeks. Values for which p<0,05 were considered significant. When compared to resting values, urinary excretion of copper and selenium decreased in exercise (p<0,05), but increased with zinc supplementation (p<0,05). Pre- and post-supplementation exercise resulted in reduced urinary zinc excretion (p<0,05). Zinc supplementation increased urinary zinc excretion in one-week intervals over the course of 4 weeks (p<0,05), and reduced selenium levels (p<0,05). When zinc is supplemented to athletes, the relation between the duration and dose of supplementation is important. The results of the study indicated that zinc does not have any negative effect on the urinary excretion of the concerned elements. It can thus be concluded that athletes may benefit from zinc support.

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.

Apoptosis of hippocampus and cerebellum induced with brain ischemia reperfusion prevented by 3',4'-dihydroxyflavonol (DiOHF).

The present study aimed to determine the effect of 3',4'-dihydroxyflavonol (DiOHF) on apoptosis in the cerebellum and hippocampus in rats with ischemia-reperfusion. A total of 38 Wistar albino male rats were used. Experimental groups were designed as Group 1-Sham; Group 2-Ischemia-reperfusion (IR), in which animals were anesthetized and carotid arteries ligated for 30 minutes (ischemia) and reperfused 30 minutes; Group 3- IR + DiOHF (10 mg/kg); Group 4- Ischemia + DiOHF (10 mg/kg) + reperfusion; Group 5-DiOHF + IR. DiOHF was supplemented as 10 mg/kg by intraperitoneal injection 30 minutes before IR. Following application, the animals were sacrificed under general anesthetic by cervical dislocation, and the cerebellum and hippocampus tissues were analyzed for apoptosis. IR significantly increased hippocampus and cerebellum apoptosis activity, confirmed by Hematoxylin-Eosin, TUNEL labeling, and Caspase-8 activity. However, these values were significantly suppressed by the administration of DiOHF, especially when used before the ischemia and reperfusion. The results of the study show that increased apoptosis in the cerebellum and hippocampus tissue was inhibited by intraperitoneal DiOHF supplementation.