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.

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.

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.

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 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.

The effect of thyroid dysfunction and treatment on adropin, asprosin and preptin levels in rats.

OBJECTIVES: Thyroid hormones have important roles in normal development and energy regulating mechanisms as well as signaling mechanisms that affect energy consumption through central and peripheral pathways. The aim of this study was to determine the effects of thyroid dysfunction on adropin, asprosin and preptin levels in rat. METHODS: The study was performed on the 38 male Wistar-albino rats. Experiment groups were designed as follows. 1-Control, 2-Hypothyroidism; To induce hypothyroidism PTU was applied by intraperitoneal as 10 mg/kg/day for 2 weeks. 3-Hypothyroidism + Thyroxine; Previously animals were made with hypothyroidism by 1 week PTU application and then 1 week l-thyroxine was given by intraperitoneal as 1.5 mg/kg/day. 4-Hyperthyroidism; Rats were made with hyperthyroidism by 3 weeks l-thyroxine (0.3 mg/kg/day). 5-Hyperthyroidism + PTU; Animals were made hyperthyroisim by l-thyroxine as groups 4, then 1 week PTU was applied to treatment of hiperthyrodism. At the end of supplementation animals were sacrificed and blood samples were collected for FT3, FT4, adropin, asprosin, preptin analysis. RESULTS: FT3 ve FT4 levels were reduced significantly in hypothyroidism while increased in hyperthyroidism (p<0.001). Hipothyrodism led to reduces adropin, asprosin and preptin levels. And also hyperthyroidism reduced adropin and preptin levels (p<0.001). CONCLUSIONS: The results of study show that experimental hypothyroidism and hyperthyroidism lead to significantly change to adropin, asprosin and preptin levels. However, correction of thyroid function caused to normals levels in asprosin and preptin.

Aquaporins and Roles in Brain Health and Brain Injury.

In the literature screening, aquaporins were found in the cerebral structures including the pia mater, choroid plexus, ependyma, piriform cortex, hippocampus, dorsal thalamus, supraoptic and suprachiasmatic nuclei, white matter and subcortical organ. Among these, the most common are AQP1, AQP4, and AQP9. The roles of aquaporins have been demonstrated in several diseases such as cerebral edema, various central nervous system tumors, Alzheimer's Disease and epilepsy. In this review, the relationship between brain/brain-injury and aquaporin, has been reviewed.

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.