The effect of homocysteine on the expression of CD36, PPARγ, and C/EBPα in adipose tissue of normal and obese mice.

The purpose of this study was to investigate the effect of homocysteine (Hcy) on CD36, PPARγ, and C/EBPα gene and protein expression in adipose tissue obtained from normal and high-calorie diet obesity models. CD36, PPARγ, and C/EBPα gene expression and protein levels in adipose tissue specimens were determined using the RT-PCR and ELISA methods, respectively. Significantly increased CD36 gene expression was observed in adipose tissue from obese mice, while Hcy significantly reduced CD36 gene expression in adipose tissue from normal and obese mice. PPARγ and C/EBPα gene expression levels decreased significantly in all groups compared to the normal group. In addition, levels of both PPARγ and C/EBPα gene expression were lower with Hcy supplementation compared to their own controls. In conclusion, Hcy's reduction of CD36 gene expression in adipose tissue may be one probable factor in hyperhomocysteinemia representing an independent risk factor for cardiovascular diseases.

Effect of a high sucrose and high fat diet in BDNF (+/-) mice on oxidative stress markers in adipose tissues.

The purpose of this study was to investigate the effects of a high fat and a high sucrosediet in wild type and BDNF (+/-) mice on oxidative stress in epididymal and subcutaneousadipose tissues by measuring different markers of oxidative stress and antioxidant enzymes. Wild type (WT) and BDNF (+/-) male mice were divided into six groups receiving fed control diet (CD), high sucrose diet (HSD), or high fat diet (HFD) for four months. Levels of 3-nitrotyrosine (3-NT) increased in the HFD-fed BDNF (+/-) mice, while 4-hydroxynonenal (4-HNE) levels increased in the CD and HFD-fed BDNF (+/-) groups. Malondialdehyde (MDA) levels decreased in subcutaneous tissue compared to epididymal adipose tissue, independently of diet type. Superoxide dismutase (SOD) activity was reduced by HFD (p < 0.05), butglutathione peroxidase (GSH-Px) activity was increased by HSD in epididymal adipose tissuein BDNF (+/-) mice (p < 0.05). GSH-Px activities was increased by CD and HFD in subcutaneous adipose tissue of BDNF (+/-) (p < 0.05). SOD2 and GSH-Px3 expressions were only decreased by HSD in epididymal and subcutaneous adipose tissues of BDNF (+/-) mice (p < 0.05). In conclusion, reduced BDNF may increase OS in epididymal adipose tissue, but not in subcutaneous adipose tissue following HSD and HFD.

Vitamin D protects against hippocampal apoptosis related with seizures induced by kainic acid and pentylenetetrazol in rats.

OBJECTIVES: The hippocampus is susceptible to damage in patients with epilepsy and in animals with seizures caused by excitotoxic agents. The effect of vitamin D on hippocampal apoptosis related with seizures has not been reported. However, epileptic patients have an increased risk of hypovitaminosis D which is most likely due to the effects of antiepileptic drugs. Therefore, in this study, it was aimed to evaluate the effects of vitamin D on hippocampal apoptosis related with seizures by using pentylenetetrazol (PTZ) and kainic acid (KA) in rats. METHODS: Male Sprague Dawley rats, aged 5.5 weeks, were randomly divided into six groups: control, vitamin D, PTZ, KA, PTZ + vitamin D and KA + vitamin D groups. The groups that received vitamin D were given 500 IU/kg of vitamin D daily for two weeks in addition to a standard diet. At the end of this period, PTZ and KA were applied to trigger seizures in the rats in the seizure groups. 24 h after the administration of PTZ and KA, the rats were decapitated. In the hippocampal region, apoptosis was assessed by TUNEL and brain-derived neurotrophic factor (BDNF), Bax, caspase-3 and c-fos activation were evaluated by immunohistochemical method. RESULTS: BDNF level increased while c-fos, Bax and caspase-3 levels decreased (p < 0.0001, in all) in the hippocampal neurons of the groups that were pre-treated with vitamin D before the administration of PTZ and KA, in comparison with the PTZ and KA groups. Vitamin D significantly decreased the number of apoptotic cells in these rats in comparison with the PTZ and KA groups (p < 0.0001). CONCLUSION: This study indicates that vitamin D has neuroprotective effects on hippocampal apoptosis induced by PTZ and KA in rats. With this study it is suggested that keeping vitamin D levels within normal limits may be beneficial for patients with epilepsy, especially children.

The Effects of Hesperidin and Quercetin on Serum Tumor Necrosis Factor-Alpha and Interleukin-6 Levels in Streptozotocin-induced Diabetes Model.

BACKGROUND: Diabetes mellitus (DM) is a metabolic disorder that occurs as a result of absolute or relative insufficiency of insulin release and/or insulin effect due to impairment of carbohydrate, fat and protein metabolism, and it is characterized by hyperglycemia and leads to various complications. OBJECTIVE: In this study, it was aimed to investigate the effects of hesperidin (HP) and quercetin, which are natural flavonoids, on serum malondialdehyde (MDA), glutathione (GSH), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) levels in rats with streptozotocin (STZ)-induced diabetes. MATERIALS AND METHODS: The experimental animals were divided into four groups, each group comprising ten rats designated as follows: Group 1 served as control rats (C); Group 2 served as diabetic rats (DM); Group 3 served as diabetic rats administered HP (DM + HP) (100 mg/kg b. w.); and Group 4 served as diabetic rats administered quercetin (DM + Q) (100 mg/kg b. w.). RESULTS: Serum MDA and GSH levels were significantly higher in STZ-induced DM group than control group (P < 0.05). In DM + HP and DM + Q groups, MDA levels were significantly decreased compared to DM groups (P < 0.05), but there was no significant difference GSH levels between DM, DM + HP, and DM + Q groups (P > 0.05). TNF-α levels in STZ-induced DM group were significantly decreased compared to control group (P < 0.05), and groups of DM + HP and DM + Q had higher serum TNF-α levels than STZ-induced DM group (P < 0.05). In STZ-induced DM group, serum IL-6 levels were decreased compared to control group (P < 0.05). CONCLUSION: As a result, in this study, we determined that HP and quercetin may play an effective role in regulating insulin metabolism metabolism in diabetes. However, considering the incompatibility of various results in the literature as well as our own results, we think that the actual role of cytokines in the pathogenesis of diabetes is one of the issues that need to be clarified in further studies. SUMMARY: Hesperidin (HP) and quercetin reduced the insulin, total cholesterol, triglyceride, low-density lipoprotein cholesterol, and malondialdehyde (MDA) serum levels and raised the glutathione (GSH) levels compared to diabetes mellitus (DM) groupSZT-induced DM increased the MDA serum levels and decreased the GSH levels compared to control groupHP and quercetin-treated rats showed higher interleukin-6 and tumor necrosis factor alpha cytokine levels than DM groupHP and quercetin may play an effective role in regulating insulin metabolism in diabetes. Abbreviations used: DM: Diabetes mellitus, MDA: Malondialdehyde, GSH: Glutathione; IL-6: Interleukin-6, TNF-α: Tumor necrosis factor alpha, HP: Hesperidin, Q; Quercetin, STZ: Streptozotocin, TC: Total cholesterol, TG: Triglyceride, HDL-C: High density lipoprotein cholesterol, LDL-C: Low density lipoprotein cholesterol, VLDL-C: Very-low-density lipoprotein cholesterol.

A morphological and biochemical evaluation of the effects of quercetin on experimental sciatic nerve damage in rats.

The present study evaluated the neuroprotective and antioxidant effects of quercetin in a rat model of sciatic nerve crush injury using histopathological, morphometric and biochemical methods. A total of 48 male Sprague Dawley rats, aged 10-12 weeks old were randomly divided into eight groups, consisting of two sham groups (S-7, S-28), three quercetin-treated groups (Q-7, Q-28; 200 mg/kg/7 days), trauma (T-7, T-28; 1 min sciatic nerve crush injury) and three trauma+quercetin groups (T+Q-7, T+Q-28; trauma+quercetin 200 mg/kg/7 days). Rats were sacrificed on day 7 or 28. Oxidant-antioxidant biochemical parameters in nerve tissues from all groups were analyzed using histopathological staining with toluidine blue and Masson's trichrome. DNA fragmentations were identified using terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling in cells from each tissue sample. Degeneration of the axons and myelin sheath, the breakdown of the concentric lamellar structure of the myelin sheath and axonal swelling were observed in groups T-7 and T-28. Myelin sheath thicknesses, nerve fiber diameters and the number of myelinated nerve fibers decreased, while the apoptotic index (AI) increased in the T-7 and T-28 groups. However, it was observed that nerve regeneration began in the T+Q-7 and T+Q-28 groups compared with the sham groups, together with the healing of cellular damage and axonal structure and a decrease in the AI. Malondialdehyde and superoxide dismutase activity did not differ significantly between the T-7 and S-7 groups. However, catalase activity significantly decreased in the T-28 group when compared with the sham 7 day group. Tissue malondialdehyde levels significantly increased, while serum catalase activity increased in the T+Q-7 group compared with the T-7 group. These results suggest that quercetin has beneficial effects on nerve regeneration and may shorten the healing period in crush-type sciatic nerve injuries.

Brain-derived neurotropic factor (BDNF) heterozygous mice are more susceptible to synaptic protein loss in cerebral cortex during high fat diet.

In this study we aimed to investigate whether reduced BDNF levels aggravate the susceptibility of the brain to hazardous effects of high fat diet. For this purpose, we fed BDNF heterozygous mice and wild type littermates with normal and high fat diet for 16 weeks. Concentrations of two synaptic proteins (SNAP-25 and PSD-95) and oxidative stress parameters (MDA, SOD, CAT) were evaluated in the cortex after diet period. Interestingly, body weights of BDNF heterozygous groups fed with control diet were higher than their littermates and heterozygous mice fed with HFD were the heaviest in all experimental groups. MDA levels were significantly elevated in both HFD groups (wild type and BDNF(+/-)). Synaptic markers PSD-95 and SNAP-25 markedly decreased in BDNF(+/-) group fed with HFD compared to other groups. In conclusion, we suggest that endogenous BDNF has an important and possibly protective role in diet-induced changes in the cortex.

[The Relationship of Interleukin-18 and Interleukin-6 Levels with Cognitive Functions in Bipolar Disorder]. / Bipolar Bozuklukta Interlökin-18 ve Interlökin-6 Sitokin Seviyelerinin Bilissel Islevler ile Iliskisi.

OBJECTIVE: Impairment in immune functions is proposed as a key factor in the cognitive decline in bipolar disorder (BD) however there is scarcity of research on the impact of inflammation on cognitive functions. Our aim is to compare IL-18 and IL-6 levels in BD patients and controls and to study the relationship between IL-18 and IL-6 levels and cognitive impairment METHOD: Thirty-six euthymic BD-I patients and 38 age, sex and educational level matched healthy controls were enrolled in the study. All participants were evaluated with neurocognitive tests. The plasma IL-6 and IL-18 levels of both groups were measured with ELISA kits. RESULTS: There was no statistically significant difference between IL-6 and IL-18 levels of patient and healthy control groups. In the patient group, IL-18 level was positively correlated with completed categories score wheras there was a negative correlation with perseverative response and perseverative errors. Moreover IL-18 level was positively correlated with immediate recall, delayed recall and learning scores while there was a negative correlation with stroop interference scores. No correlation was found between IL-6 level and neuropsychological test scores in the patient group. CONCLUSION: This is the first study that investigates the relation of IL-18 with cognitive functions. Possible detrimental or protective effects of IL-18 in BD is not yet clear, however the positive association of IL-18 level and neuropsychological test scores might indicate a neuroprotective role of IL-18 in the euthymic period of BD which is the closest state to physiological condition.

The effect of hesperidin and quercetin on oxidative stress, NF-κB and SIRT1 levels in a STZ-induced experimental diabetes model.

OBJECTIVE: The aim of this study is to investigate the roles of SIRT1 and NF-κB in the pathogenesis of diabetes mellitus in rats with STZ-induced diabetes and determine the effects of hesperidin and quercetin on oxidative stress and on the levels of SIRT1 and NF-κB. MATERIALS AND METHODS: The experimental animals were divided into four groups, each group comprising ten rats designated as follows: group 1 served as control rats (C); group 2 served as diabetic rats (DM); group 3 served as diabetic rats administered hesperidin (DM+HSP) (100mg/kg b.w.) in aqueous suspension orally for 15 days; and group 4 served as diabetic rats administered quercetin (DM+Q) (100mg/kg b.w.) in aqueous suspension orally for 15 days. RESULTS: In diabetic group, liver and kidney SIRT1, SOD and CAT activities were significantly lower than control group (p<0.05). Hesperidin and quercetin caused significant increase in the SIRT1, SOD and CAT activities of both DM+HP and DM+Q groups kidney tissues compared to DM group (p<0.05). Liver SOD activies were not found to differ significantly between DM, DM+Q and DM+HP groups (p>0.05). In DM+HP group, liver CAT activities were significantly higher than DM (p<0.05), but there was no significant difference in liver CAT activities between DM and DM+Q (p>0.05). In diabetic group, liver and kidney NF-κB and MDA levels were increased compared to control group (p<0.05), and groups of DM+HP and DM+Q had lower NF-κB and MDA levels than diabetic group (p<0.05). CONCLUSION: As a conclusion, based on the results we obtained from this study and the literature data discussed above, we determined in STZ-induced diabetic rats that, increased glucose levels and liver and kidney damage markers decreased significantly after administration of hesperedin and quercetin, and that oxidative stress and NF-κB levels increased while SIRT1 levels decreased in the diabetic group.

The effects of edaravone in ketamine-induced model of mania in rats.

Bipolar disorder is a chronic disease characterized by recurring episodes of mania and depression that can lead to disability. This study investigates the protective effects of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a drug with well-known antioxidant properties, in a model of mania induced by ketamine in rats. Locomotor activity was assessed in the open-field test. Superoxide dismutase (SOD), catalase (CAT) and thiobarbituric acid reactive substances (TBARS) levels were measured in order to evaluate oxidative damage in the rat hippocampus and prefrontal cortex. Increased locomotor activity (hyperlocomotion) was observed at the open-field test with ketamine treatment (25 mg/kg, i.p., 8 days). Edaravone (18 mg/kg) treatment did not prevent hyperlocomotion in the mania model induced with ketamine in rats, but lithium chloride (47.5 mg/kg, i.p., positive control) did prevent hyperlocomotion. Edaravone and lithium chloride treatments were found to reduce the increase in SOD and CAT activity following ketamine administration in a non-significant manner but caused no change in TBARS levels.

Determination of skin wound age by using cytokines as potential markers.

Interleukin-1 beta (IL-1ß), IL-6, tumour necrosis factor-alpha (TNF-α) and epidermal growth factor (EGF) play important roles in the wound healing process. In the present study, human wound specimens (n = 50) were collected from cases of death due to injuries from firearms, penetrating trauma by sharp objects and blunt trauma with a known time of injury and death identified by forensic autopsy. Full-thickness tissue specimens were obtained from injured skin sites, and equally sized intact tissues obtained from the same person were used as controls. Protein determination was performed using ELISA according to the Bradford method for each specimen, and results were provided for individual proteins. IL-1ß levels did not reach statistical significance in any of the wound groups and were not markedly higher than those in the control group. However, IL-6 showed a biphasic pattern and reached statistical significance in the group with wounds less than 30 min old and in the group with wounds more than 18 h old. IL-6 was consistently higher in all wound groups than in the control group. TNF-α showed a statistically significant increase within the first 30 min and remained at a high level in all groups except for those with wounds 2-4 h old. On the other hand, EGF was high in all groups excluding those with wounds 2-4 h old and more than 18 h old, but statistical significance was not reached. Our results suggest that IL-6 and TNF-α in particular may be used as early-phase markers. We believe that IL-1ß and EGF should be more extensively evaluated in further studies.

Assessment of oxidative stress parameters of brain-derived neurotrophic factor heterozygous mice in acute stress model.

OBJECTIVES: Exposing to stress may be associated with increased production of reactive oxygen species (ROS). Therefore, high level of oxidative stress may eventually give rise to accumulation of oxidative damage and development of numerous neurodegenerative diseases. It has been presented that brain-derived neurotrophic factor (BDNF) supports neurons against various neurodegenerative conditions. Lately, there has been growing evidence that changes in the cerebral neurotrophic support and especially in the BDNF expression and its engagement with ROS might be important in various disorders and neurodegenerative diseases. Hence, we aimed to investigate protective effects of BDNF against stress-induced oxidative damage. MATERIALS AND METHODS: Five- to six-month-old male wild-type and BDNF knock-down mice were used in this study. Activities of catalase (CAT) and superoxide dismutase (SOD) enzymes, and the amount of malondialdehyde (MDA) were assessed in the cerebral homogenates of studied groups in response to acute restraint stress. RESULTS: Exposing to acute physiological stress led to significant elevation in the markers of oxidative stress in the cerebral cortexes of experimental groups. CONCLUSION: As BDNF-deficient mice were observed to be more susceptible to stress-induced oxidative damage, it can be suggested that there is a direct interplay between oxidative stress indicators and BDNF levels in the brain.

Investigation of the expression of irisin and some cachectic factors in mice with experimentally induced gastric cancer.

BACKGROUND: The purpose of this study was to determine whether irisin is secreted by gastric tumor cells experimentally induced in mice, and also if it has any effect on cancer cachexia. DESIGN AND METHODS: 12 out of 60 BALB/c mice were used as a control group, while N-nitroso-N-methylurea (MNU) was administered orally to the remaining 48. After 150 days, the surviving mice were sacrificed by decapitation, blood and stomach, skeletal muscle, brown and white adipose tissue specimens were collected. Following histopathological evaluation of the stomach tissues, it was decided to create four groups, one control group and three consisting of mice administered MNU, no cancer, pre-cancer and cancer. Gene expression analyses of fibronectin type III domain containing protein 5 (FNDC5) and some cachexia-related proteins were performed in tissue samples, while levels of irisin, and various inflammatory and tumor markers together with cachectic factors were determined in serum samples. RESULTS: The levels of inflammatory, tumor markers and cachectic factors in serum samples were significantly higher in the cancer group compared with the control group. No expression of FNDC5 or zinc-α-2 glycoprotein, a cachectic factor, was observed in gastric tissues from the control and MNU groups, whereas significantly increased FNDC5 expression was determined in the both white and brown adipose tissues from the cancer group. CONCLUSION: Increased FNDC5 expression in white and brown adipose tissues may have a cachectic effect in mice with induced cancer. However, it is not possible to explain the mechanism of the relationship between irisin and gastric cancer development on the basis of the results of this study.

Investigation of N-acetylcysteine on contralateral testis tissue injury by experimental testicular torsion: long-term effect.

BACKGROUND: The aim of the study was to investigate long-term effects of N-acetylcysteine (NAC) on contralateral testes by experimental testicular torsion using histopathologic and biochemical parameters. METHODS: Eighteen rats were randomized and divided into 3 groups. In group 1, the control group (C), laparotomy was performed and the left and right testes were excised 2 months later. In group 2, the torsion and detorsion group (T), the torsion was performed by rotating the left testis 720° to clockwise direction, and then 4 hours later, detorsion was performed; 2 months later, contralateral testes were removed. In group 3, the NAC adding torsion and detorsion group (T+NAC), the torsion was performed by rotating the left testis 720° to clockwise direction, and then 4 hours later, detorsion was performed. N-acetylcysteine was given intraperitoneally 30 minutes before detorsion and following 5 days after detorsion. RESULTS: GPx activities were increased in the T and T+NAC groups compared with the control (P = .008 and P = .016, respectively). Seminiferous tubule diameter thickness is decreased in the torsion group compared with the control group and decreased in the T+NAC group compared with the torsion group (P < .05). CONCLUSION: In the long term as implied from the histopathologic findings, NAC has beneficial effects against contralateral testis tissue injury induced by testicular torsion.