Radiographic Investigation of Lumbar Vertebrae in Patients with Flexion and Extension Movement Disorder Syndrome.

Objectives: The kinesiopathology model is a new rehabilitation model classifying, evaluating, and treating patients with non-specific back pain. Sahrmann proposed this model based on movement disorder syndromes. The present cross-sectional study aimed to evaluate the radiograph of the linear and angular displacement of the lumbar spine in patients with lumbar flexion impairment syndrome (LFIS) and lumbar extension impairment syndrome (LEIS). Methods: In this study, 50 adults aged 18-46 years were enrolled, including 25 patients with LFIS and 25 with LEIS. The eligible participants were referred to the radiology department for radiography in the common position of neutral, full extension, and full flexion position while standing. The White and Panjabi's method was used to measure the linear and angular displacements. Moreover, pain intensity was assessed using the visual analogue scale, and functional disability was investigated using a modified Oswestry Disability Questionnaire. Results: The parameter of the linear displacement at the L3-L4 level was significantly different between the two groups (P=0.02). The mean duration of low back pain was longer in the LEIS, compared to the LFIS group (P=0.01). Conclusion: In patients with LEIS, compensatory responses occur that cause less linear displacement at the L3-L4 level, compared to the patients with LFIS. Therefore, it is important to design appropriate exercises to better control the linear displacement at the L3-L4 level during the full range of motion in patients with LFIS.

Combining clinical exams can better predict lumbar spine radiographic instability.

BACKGROUND/OBJECTIVES: Several clinical tests have been proposed to diagnose lumbar instability, but their accuracy is still in question. The primary purpose of this study was to evaluate the diagnostic accuracy of the clinical lumbar instability tests. The secondary goal was to design a model to detect lumbar instability. DESIGN: A prospective diagnostic cross-sectional study. METHOD: A sample of 202 patients with chronic low back pain were participated in the study. Five lumbar instability tests including Aberrant movement, Passive lumbar extension, Prone segmental instability, H and I and pheasant tests were compared to flexion/extension radiography as the gold standard for diagnosing lumbar instability using two by two tables. Multiple Logistic Regression analysis was applied to develop a model using demographic information as well as the patients' pain intensity, disability level, lumbar lordosis and the clinical tests. RESULTS: Among the five examined tests, Prone segmental instability, H and I and pheasant tests showed very small likelihood ratios and diagnostic odd's ratio. The largest values were for H and I test with the positive likelihood ratio of 1.28 (95% CI: 0.72 to 2.29) and diagnostic odd's ratio of 1.37 (95% CI: 0.66 to 2.83); the diagnostic accuracy measures were smaller for the other studied clinical tests. The model was developed using weight (t = 1.15, p = 0.03) and lumbar lordosis (t = 3.04, p = 0.00) (which showed a significant relationship with lumbar instability) and prone segmental instability test. The final model has the positive likelihood ratio of 2.07 (95% CI: 1.41 to 3.05) and diagnostic odd's ratio of 3.77 (95% CI: 2.03 to 7.01). CONCLUSION: Each individual test had very small to no power in discriminating patients with lumbar instability. The developed model just slightly improved the accuracy of radiological instability detection.

Zingiber officinale ameliorates Alzheimer's disease and Cognitive Impairments: Lessons from preclinical studies.

Alzheimer's disease (AD) is a neurodegenerative condition mostly communal in people of advanced years accompanying various dysfunctionalities especially cognitive impairments. A number of cellular damages, such as amyloid-beta aggregation, tau protein hyperphosphorylation, some neurotransmitter imbalances, apoptosis, oxidative stress, and inflammatory responses are responsible for AD incidence. As a reason for inadequate efficacy, side effects, and pharmacokinetic problems of conventional drugs used for AD, the discovery of novel therapeutic agents with multi-targeted potential is desirable. Protective properties of phytochemicals combat numerous diseases and their vast acceptance and demand in human beings encouraged scientists to assess their effective activities. Zingiber officinale, gingerol, shogaol, and borneol were evaluated against memory impairments. Online databases including; Web of Science, Scopus, Embase, Pubmed, ProQuest, ScienceDirect, and Cochrane Library were searched until 3th February 2020. In vitro, in vivo, and clinical studies are included after screening their eligibility. Mostly interventive mechanisms such as; oxidative stress, neuroinflammation, and apoptosis are described. Correlation between the pathogenesis of AD and signaling pathways is explicated. Results and scores of cognition measurements are clarified due to in vivo studies and clinical trials. Some traditional aspects of consuming ginger in AD are also mentioned in the present review. In accumulation ginger and its components possess great potency for improving and abrogating memory dysfunctions but conducting further studies to evaluate their pharmacological and pharmaceutical aspects is required.

Garlic (Allium sativum) improves anxiety- and depressive-related behaviors and brain oxidative stress in diabetic rats.

This study investigated the effects of garlic on anxiety- and depression-related behaviors and brain oxidative markers in streptozotocin (STZ)-induced diabetes in rats. Fifty-six male Wistar rats were randomly divided into seven experimental groups (n = 8/group): control, diabetic + saline, diabetic + garlic, diabetic + imipramine, and diabetic + diazepam groups. Animals received garlic homogenate (0.1, 0.25, and 0.5 g/kg) for 10 days. At the end of the treatments, anxiety- and depressive-related behaviors were evaluated by elevated plus maze (EPM) and forced swimming test (FST), respectively. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and malondialdehyde (MDA) levels were measured in the brain. Diabetic + garlic (0.5 g/kg) group showed lower anxiety- and- depressive-like behaviors as compared to the diabetic rats. Furthermore, garlic treatment (0.5 g/kg) attenuated MDA levels and enhanced SOD and GPx activities in the brain. Our findings indicate that garlic alleviates anxiety- and depression-related behaviors in the diabetic rats possibly by attenuation of brain oxidative stress.

Effects of topical erythropoietin on healing experimentally-induced avascular scleral damage in a rabbit model.

The present study was designed to investigate the effect of topical erythropoietin on the healing process of induced necrotizing scleritis and to evaluate the ocular side effects of this treatment modality in a rabbit model. Necrotizing scleritis was induced in 8 New Zealand albino rabbits. The animals were then randomly divided into one of two groups: a treated group administered a topical erythropoietin-containing cellulose-based gel every 8 h or a control group treated with a cellulose-based gel without erythropoietin every 8 h. The sizes of the lesions measured at different time points were compared between the groups. After three months, the rabbits' eyes were enucleated and histologically and immunohistochemically evaluated for angiogenesis and apoptosis. The lesions were completely vascularized in all eyes of the treated group and 50% of eyes of the control group. The mean interval from the induction of scleral necrosis to a complete improvement was 28 days in the treated group and 62.5 days in the control group (P = 0.04). Histological examination revealed that erythropoietin enhanced the improvement of necrotizing scleritis by stimulating angiogenesis and reducing apoptosis. Neovascularization of the cornea, iris, or retina was not observed in the treated group. We observed a significantly faster recovery to complete improvement of necrotizing scleritis in rabbit eyes treated with erythropoietin compared to those of the control group. Treated eyes had a higher rate of complete healing and had no ocular safety concerns. This therapeutic modality represents a promising treatment for scleral necrosis following various types of ocular surgery.

Effect of troxerutin on apelin-13, apelin receptors (APJ), and ovarian histological changes in the offspring of high-fat diet fed rats.

OBJECTIVES: Maternal high-fat diet (HFD) consumption has been linked to metabolic disorders and reproductive dysfunctions in offspring. Troxerutin (TRO) has anti-hyperlipidemic, anti-oxidant, and anti-inflammatory effects. This study examined the effects of TRO on apelin-13, its receptors mRNA and ovarian histological changes in the offspring of HFD fed rats. MATERIALS AND METHODS: Female Wistar rats were randomly divided into control diet (CD) or HFD groups and received these diets for eight weeks. After mating, dams were assigned into four subgroups: CD, CD + TRO, HFD, and HFD + TRO, and received their respective diets until the end of lactation. Troxerutin (150 mg/kg/day) was gavaged in the CD + TRO and HFD + TRO groups during pregnancy. On the postnatal day (PND) 21 all female offspring were separated and fed CD until PND 90. On PND 90 animals were sacrificed and ovarian tissue samples were collected for further evaluation. RESULTS: Results showed that HFD significantly decreased serum apelin-13 in the female offspring of the HFD dams, which was significantly reversed by TRO. Moreover, real-time polymerase chain reaction (PCR) analysis revealed that TRO treatment significantly decreased the ovarian mRNA expression of the apelin-13 receptor in the troxerutin-received offspring. Furthermore, histological examination revealed that TRO increased the number of atretic follicles in the ovaries of HFD+TRO offspring. CONCLUSION: Maternal high fat feeding compromises ovarian health including follicular growth and development in the adult offspring and troxerutin treatment improved negative effects of maternal HFD on the apelin-13 level and ovarian development of offspring.

The effect of adding ethanolic saffron petal extract (SPE) and vitamin E on growth performance, blood metabolites and antioxidant status in Baluchi male lambs.

OBJECTIVE: This study investigated the effects of the administration of ethanolic saffron petal extract (SPE) and vitamin E on growth performance, blood metabolites and antioxidant status in Baluchi lambs. METHODS: Thirty-two Baluchi male lambs (35.22±5.75 kg) were randomly divided into 4 groups. The 1st (control), 2nd (ISPE) and 3rd (Vit. E) groups were respectively injected subcutaneously with either physiological saline (5 ml), SPE (25 mg/kg BW) or DL-α-tocopheryl acetate (225 IU) once a week. An oral dose of SPE (500 mg/kg BW) was also administered to the 4th group (OSPE). Feed intake and body weight were measured for 42 days and blood samples were taken on days 1, 14, 28 and 42. The lambs were slaughtered and tissue samples were taken. RESULTS: Growth performance and many blood metabolites were not affected (p>0.05) by the treatments. Cholesterol of plasma in the ISPE and Vit. E groups was similar and less (p<0.01) than both the OSPE and control groups. Although there was no significant difference between the control and other groups for plasma triglyceride, the ISPE group showed lower (p<0.05) triglyceride than the OSPE and Vit. E groups. The highest (p<0.01) plasma glutathione peroxidase (GPx) was detected in the OSPE group, while the ISPE and Vit. E groups showed higher (p<0.01) superoxide dismutase (SOD) of plasma than the control. Malondialdehyde of plasma in the ISPE group was lower (p<0.05) than the OSPE. No differences (p>0.05) were observed among the groups for antioxidant status of both of the longissimus dorsi muscle and liver. However, the activity of GPx in the kidney and heart, as well as SOD activity in the kidney, were influenced (p≤0.01) by the treatments. CONCLUSION: Adding ethanolic SPE improved antioxidant status and lowered lipids oxidation in lambs. The SPE and vitamin E demonstrated similar effects on antioxidant status in lambs.

Gene Silencing of TGFßRII Can Inhibit Glioblastoma Cell Growth

Objective: Glioblastoma (GBM) is the most malignant and aggressive type of glioma, associated with a high rate of mortality. The transforming growth factor-ß receptor II (TGFß RII) is involved in glioma initiation and progression. On the other hand, TGFß RII silencing is critical to the inhibition of GBM. Therefore, we aimed to determine the effects of specific TGFß RII siRNA on the survival of U-373MG cells. Methods: TGFß RII siRNA was transfected, and qRT-PCR was performed to examine TGFß RII mRNA expression. Cell survival was determined using colorimetric MTT assay, and platelet-derived growth factor-BB (PDGF-BB) level was measured in the culture supernatant using ELISA assay. Result: Our findings indicated that specific siRNAs could dose-dependently suppress TGFß RII mRNA expression after 48 hours. In addition, treatment with TGFß RII siRNA significantly reduced tumor cell survival and decreased the amount of PDGF-BB protein in the cell culture supernatant. Conclusion: Our results suggest that TGFß RII silencing can be a promising complementary treatment for glioma.

Effects of Diet-Induced Obesity on Tracheal Responsiveness to Methacholine, Tracheal Visfatin Level, and Lung Histological Changes in Ovalbumin-Sensitized Female Wistar Rats.

Many studies have shown a close relationship between obesity and asthma severity. In the present study, the effects of diet-induced obesity were examined on airway responsiveness to methacholine in addition to visfatin level in female Wistar rats' tracheae after sensitization with ovalbumin. The rats were divided into four groups: control with normal diet (ND), ovalbumin (OVA)-sensitized with normal diet (S + ND), high-fat diet (HFD), and OVA-sensitized with a high-fat diet (S + HFD). The animals were fed for 8 weeks with standard pelts or high-fat diet and then sensitized and challenged with OVA or saline for another 4 weeks. At the end of the study, the tracheae were isolated and assessed for airway responsiveness and visfatin protein levels. Diet-induced obesity groups developed increased weight and obesity indices (p < 0.001). After sensitization with OVA and diet-induced obesity, there were marked leftward shifts in methacholine concentration-response curves in S + HFD group compared to other groups. Also, maximum response was the highest (p < 0.05 to p < 0.001), EC50 was the lowest (p < 0.05 to p < 0.001), and visfatin protein level was the highest (p < 0.05 to p < 0.01) in S + HFD. According to results, diet-induced obesity caused airway hyperresponsiveness to methacholine and enhanced visfatin protein levels in the tracheae of ovalbumin-sensitized female rats. Our results suggested that, in obese ovalbumin-sensitized conditions in female rats, the local production of adipocytokines, such as visfatin, may be increased, resulting in the deterioration of inflammation in lungs. This finding shows a possible mechanism for the altered phenotype in obesity-ovalbumin sensitization conditions in female rats.

Effects of Chronic Ghrelin Treatment on Hypoxia-Induced Brain Oxidative Stress and Inflammation in a Rat Normobaric Chronic Hypoxia Model.

Omrani, Hasan, Mohammad Reza Alipour, Fereshteh Farajdokht, Hadi Ebrahimi, Mehran Mesgari Abbasi, and Gisou Mohaddes. Effects of chronic ghrelin treatment on hypoxia-induced brain oxidative stress and inflammation in a rat normobaric chronic hypoxia model. High Alt Med Biol. 18:145-151, 2017. AIM: This study aimed to evaluate the probable antioxidant effects of ghrelin in the brain and serum and its effect on tumor necrosis factor-alpha (TNF-α) levels in the brain in a model of chronic systemic hypoxia in rats. METHODS: Systemic hypoxia was induced by a normobaric hypoxic chamber (O2 11%) for ten days. Adult male Wistar rats were divided into control (C), chronic ghrelin (80 µg/kg/10 days) (Ghr), chronic hypoxia (CH), and CH and ghrelin (80 µg/kg/ip/10 days) (CH + Gh) groups. The activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and malondialdehyde (MDA), total antioxidant capacity, and TNF-α levels were assessed in the serum and brain tissue. RESULTS: Our results showed that chronic ghrelin administration attenuated the CH-increased oxidative stress by decreasing MDA levels in the serum and brain tissue. Moreover, ghrelin enhanced the antioxidant defense against hypoxia-induced oxidative stress in the serum and brain tissue. Brain TNF-α levels in CH did not change significantly; however, ghrelin significantly (p < 0.001) decreased it. CONCLUSION: These results indicated that ghrelin promoted antioxidative and anti-inflammatory defense under chronic exposure to hypoxia. Therefore, ghrelin might be used as a potential therapy in normobaric hypoxia and oxidative stress induced by CH.

Influance of regular swimming on serum levels of CRP, IL-6, TNF-α in high-fat diet-induced type 2 diabetic rats.

Due to key role of inflammation in pathogenesis of type 2 diabetes mellitus (T2DM), aim of this study was evaluating the influance of regular swimming on serum levels of C-reactive protein (CRP), interlukin-6 (IL-6), tumor necrosis factor-α (TNF-α) in high-fat diet-induced diabetic rats. Fourty male Wistar rats were randomly divided into control, diabetic, exercise and diabetic-exercise groups (n = 10). Diabetes was induced by high-fat diet and streptozotocin (35 mg/kg, i.p.). In exercise groups, after induction of diabetes, animals were subjected to swimming (60 min/5 days a week) for 10 weeks. At the end of training, rats were anestatized and blood samples and pancreatic tissues were collected and used for evaluation of CRP, IL-6, TNF-α and pancreatic histopatholology. Our results showed significantly increase in lymphocytes, monocytes and decrease in neutrophils in diabetic rats (p < 0.01), which these parameters significantly reversed to control levels by induction of swimming (p < 0.01). In diabetic group, the levels of CRP, IL-6 and TNF-α increased (p < 0.01), and swimming decreased these factors significantly. Histopathological results of this study also showed that swimming can prevent damage induced by diabetes. The present study indicates that swim training is associated with improved inflammation and inflammatory mediators and pancreatic damage.

Effect of Alpha-Hederin, the active constituent of Nigella sativa, on miRNA-126, IL-13 mRNA levels and inflammation of lungs in ovalbumin-sensitized male rats.

OBJECTIVE: In previous studies the therapeutic effects of Nigella sativa have been demonstrated on asthmatic animals. In the present study, the preventive effect of single dose of alpha-hederin, its active constituent, has been evaluated on lung inflammation and some inflammatory mediators in lungs of ovalbumin sensitized rat in order to elicit its mechanism. MATERIALS AND METHODS: Forty rats were randomly grouped in 4 groups; control (C), sensitized (S), sensitized pretreated groups with thymoquinone (3 mg/kg i.p., S+TQ) and alpha-hederin (0.02 mg/kg i.p., S+AH). Levels of IL-13 mRNA and miRNA-126 in lung tissue and its pathological changes in each group were assessed. RESULTS: Elevated levels of miRNA-126, IL-13 mRNA and pathological changes were observed in the sensitized group compared to the control group (p<0.001 to p<0.05). All of these factors were significantly reduced in S+TQ and S+AH groups in comparison to S group (p<0.001 to p<0.05). Although alpha-hederin decreased the levels of miRNA-126, IL-13 mRNA and pathological changes in comparison with thymoquinone, the results were statistically not significant. CONCLUSION: The results suggested that alpha-hederin had preventive effect on sensitized rats like thymoquinone. It may intervene in miRNA-126 expression, which consequently could interfere with IL-13 secretion pathway leading to a reduction in inflammatory responses.

Effect of α-Hederin on IL-2 and IL-17 mRNA and miRNA-133a Levels in Lungs of Ovalbumin-Sensitized Male Rats.

α-hederin, a saponin that is a major constituent of English Ivy (Hedera helix) is effective in the treatment of asthma. In the present study, the effect of α-hederin on lung tissue pathology and the levels of the inflammatory mediators; IL-2 mRNA, IL-17 mRNA, and MicroRNAs (miRNA)-133a was evaluated in a rat ovalbumin (OVA)-sensitized model of asthma. Rats were divided randomly into control (C), OVA-sensitized (S), OVA-sensitized pretreated with the antioxidant, thymoquinone (3 mg/kg, S + TQ) or OVA-sensitized pretreated with α-hederin (0.02 mg/kg, S + AH) groups. Levels of IL-2 and IL-17 mRNA were higher in the OVA-sensitized group than controls while the level of miRNA-133a gene expression was lower. IL-2 mRNA and miRNA-133a gene expression in the S + TQ group was higher than in the control and OVA-sensitized groups while the level of IL-17 mRNA in the S + TQ group was lower than in the OVA-sensitized group. Pretreatment with α-hederin decreased IL-17 mRNA levels and increased miRNA-133a gene expression compared with OVA-sensitized animals. All pathological changes in pretreated groups were lower than the OVA-sensitized group. These results showed a beneficial effect of α-hederin in OVA-sensitized rats, suggesting that α-hederin affects the IL-2 and IL-17 secretion pathways, altering miRNA-133a expression.

Enduring effects of post-weaning rearing condition on depressive- and anxiety-like behaviors and motor activity in male rats.

Environmental manipulation at early critical periods could have long-lasting effects. In spite of the great interest in the biological effects of the environmental condition so far, its long-lasting effects are less documented. This study looks at the enduring effects of rearing condition on tasks that measure affective responses and exploratory behavior in male Wistar rats. The animals were reared from weaning to adulthood in an enriched environment, standard laboratory condition, or isolated condition. Then, all rats were housed in standard laboratory cages to provide a common environment, and successively exposed to different tests between 0 and 11 weeks post-manipulation. The open field test indicated a more efficient exploratory behavior in the enriched group, and an enhanced spontaneous motor activity in both standard and isolated groups. In addition, rats reared in standard condition showed heightened motor activity in forced swimming test and elevated plus maze. Forced swimming test showed an antidepressive-like effect in the enriched environment group by increased climbing behavior. In respect to the anxiety behavior, environmental enrichment improved threat detection ability. It is concluded that rearing condition from weaning to adulthood has important and long-lasting effects on depressive- and anxiety-like and exploratory behaviors as well as motor activity.

Ghrelin increases lymphocytes in chronic normobaric hypoxia.

PURPOSE: Hypoxia is a condition of decreased availability of oxygen. To adapt hypoxia, some changes in blood cells occur in the body. The aim of this study was to evaluate the effect of ghrelin on different types of blood cell in normobaric hypoxia situation. METHODS: Thirty-two animals were divided in 4 groups (n=8): control (C), ghrelin (G), hypoxia (H), and hypoxic animals that received ghrelin (H+G). Hypoxia (11%) was induced by an Environmental Chamber System GO2 Altitude. Animals in ghrelin groups received a subcutaneous injection of ghrelin (150 μg/kg/day) for 14 days. RESULTS: Our results show that ghrelin significantly (p<0.05) increased RBC and Hct levels, whereas it significantly (p<0.05) decreased lymphocytes in the blood. RBC, Hct, Hb concentration, platelet and MCV increased significantly (p<0.05) in hypoxic conditions but lymphocytes, monocytes and Polymorphonuclears did not show any significant changes. Platelets had a significant (p<0.05) decrease in hypoxic conditions and ghrelin administration in hypoxic conditions could increase lymphocyte levels significantly (p<0.05). CONCLUSION: Effect of ghrelin on blood cells could be related to blood oxygen level. Ghrelin in normal oxygen conditions increases RBC and Hct levels but decreases lymphocytes, whereas in hypoxic conditions, ghrelin increases blood lymphocytes.

Anti-arrhythmic effect of diosgenin in reperfusion-induced myocardial injury in a rat model: activation of nitric oxide system and mitochondrial KATP channel.

This study was designed to investigate the anti-arrhythmic effect of diosgenin preconditioning in myocardial reperfusion injury in rat, focusing on the involvement of the nitric oxide (NO) system and mitochondrial ATP-dependent potassium (mitoKATP) channels in this scenario. After isolation of the hearts of male Wister rats, the study was conducted in an isolated buffer-perfused heart model. Global ischemia (for 30 min) was induced by interruption of the aortic supply, which was followed by 90-min reperfusion. Throughout the experiment, the electrocardiograms of hearts were monitored using three golden surface electrodes connected to a data acquisition system. Arrhythmias were assessed based on the Lambeth convention and were categorized as number, duration and incidence of ventricular tachycardia (VT), ventricular fibrillation (VF), and premature ventricular complexes (PVC), and arrhythmic score. Additionally, lactate dehydrogenase (LDH) levels in coronary effluent were estimated colorimetrically. Diosgenin pre-administration for 20 min before ischemia reduced the LDH release into the coronary effluent, as compared with control hearts (P < 0.05). In addition, the diosgenin-receiving group showed a lower number of PVC, VT and VF, a reduced duration and incidence of VT and VF, and less severe arrhythmia at reperfusion phase, in comparison with controls. Blocking the mitoKATP channels using 5-hydroxydecanoate as well as inhibiting the NO system through prior administration of L-NAME significantly reduced the positive effects of diosgenin. Our finding showed that pre-administration of diosgenin could provide cardioprotection through anti-arrhythmic effects against ischemia-reperfusion (I/R) injury in isolated rat hearts. In addition, mitoKATP channels and NO system may be the key players in diosgenin-induced cardioprotective mechanisms.

Diosgenin attenuates inflammatory response induced by myocardial reperfusion injury: role of mitochondrial ATP-sensitive potassium channels

Reperfusion injury is one of the main reasons of cardiac disease morbidity. Phytopharmaceuticals are gaining importance in modern medicine of cardioprotection because of their multiplex capacity. The aim of this study was to investigate the effect of diosgenin on the inflammatory response induced by myocardial ischemia and reperfusion injury and the role of mitochondrial ATP-sensitive potassium (mitoKATP) channels in this regard. Wistar rats (250-300 g) were used in this study. The Langendorff-perfused hearts of animals were subjected to a 30-min global ischemia followed by a 90-min reperfusion. The lactate dehydrogenase (LDH) release was measured by spectrophotometry. The levels of inflammatory mediators tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and IL-6 in the supernatant of heart’s left ventricle were measured using an enzyme-linked immunosorbent assay rat specific ELISA kit. The LDH release into the coronary effluent during reperfusion was significantly decreased, and cardiac contractility significantly improved by diosgenin preadministration as compared with those of control or Cremophor-EL (solvent of diosgenin) groups (398 ± 48 vs. 665 ± 65 or 650 ± 73 ml/min) (P < 0.01). Administration of diosgenin before the main ischemia significantly reduced the levels of IL-6 (P < 0.05), IL-1β, and TNF-α (P < 0.01) in the reperfusion phase of diosgenin-treated hearts as compared with untreated control hearts. Inhibition of mitoKATP channels by 5-hydroxydecanoate significantly reverses the cardioprotective effects of diosgenin (P < 0.05). The findings of the present study indicate that preconditioning with diosgenin may induce cardioprotective effect against reperfusion injury through reducing the production of inflammatory mediators and activating the mitoKATP channels

Diosgenin attenuates inflammatory response induced by myocardial reperfusion injury: role of mitochondrial ATP-sensitive potassium channels.

Reperfusion injury is one of the main reasons of cardiac disease morbidity. Phytopharmaceuticals are gaining importance in modern medicine of cardioprotection because of their multiplex capacity. The aim of this study was to investigate the effect of diosgenin on the inflammatory response induced by myocardial ischemia and reperfusion injury and the role of mitochondrial ATP-sensitive potassium (mitoKATP) channels in this regard. Wistar rats (250-300 g) were used in this study. The Langendorff-perfused hearts of animals were subjected to a 30-min global ischemia followed by a 90-min reperfusion. The lactate dehydrogenase (LDH) release was measured by spectrophotometry. The levels of inflammatory mediators tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), and IL-6 in the supernatant of heart's left ventricle were measured using an enzyme-linked immunosorbent assay rat specific ELISA kit. The LDH release into the coronary effluent during reperfusion was significantly decreased, and cardiac contractility significantly improved by diosgenin preadministration as compared with those of control or Cremophor-EL (solvent of diosgenin) groups (398 ± 48 vs. 665 ± 65 or 650 ± 73 ml/min) (P < 0.01). Administration of diosgenin before the main ischemia significantly reduced the levels of IL-6 (P < 0.05), IL-1ß, and TNF-α (P < 0.01) in the reperfusion phase of diosgenin-treated hearts as compared with untreated control hearts. Inhibition of mitoKATP channels by 5-hydroxydecanoate significantly reverses the cardioprotective effects of diosgenin (P < 0.05). The findings of the present study indicate that preconditioning with diosgenin may induce cardioprotective effect against reperfusion injury through reducing the production of inflammatory mediators and activating the mitoKATP channels.

NPY Receptors Blockade Prevents Anticonvulsant Action of Ghrelin in the Hippocampus of Rat.

PURPOSE: Ghrelin has been shown to have antiepileptic function. However, the underlying mechanisms by which, ghrelin exerts its antiepileptic effects are still unclear. In the present study, we investigated whether neuropeptide Y (NPY) mediates ghrelin anticonvulsant effect in the brain through its Y1, Y2 or Y5 receptors. METHODS: Male Wistar rats were bilaterally microinjected with ghrelin 0.3 nmol/µl/side and NPY antagonists; GR231118 (Y1 receptor antagonist), BIIE0246 (Y2 receptor antagonist), CGP71683 (Y5 receptor antagonist) or solvents (Saline, DMSO) into the dorsal hippocampus 20 minutes before ghrelin administration. Thirty minutes after ghrelin microinjection, a single convulsive dose of pentylenetetrazole (PTZ) (50 mg/kg) was injected intraperitoneally (ip). Afterwards, duration of seizure and total seizure score (TSS) were assessed for 30 minutes in all animals. RESULTS: Intrahippocampal injection of 0.3 nmol/µl/side ghrelin decreased duration of seizure and TSS induced by PTZ. The suppression of both duration (p<0.001) and TSS (p<0.001) induced by ghrelin in hippocampus were significantly blocked by GR231118 (10 µg/µl/side), BIIE0246 (400 pmol/µl/side) and CGP 71683A (5 nmol/µl/side). CONCLUSION: Our findings suggest that NPY Y1, Y2 and Y5 receptors in the hippocampus may somehow mediate the anticonvulsive action of ghrelin. Therefore, it is possible to speculate that ghrelin acts in the hippocampus to modulate seizures via NPY.

GABAB Receptor Blockade Prevents Antiepileptic Action of Ghrelin in the Rat Hippocampus.

PURPOSE: Ghrelin has been shown to have antiepileptic function. However, the underlying mechanisms by which, ghrelin exerts its antiepileptic effects are still unclear. In the present study; we investigated antiepileptic mechanism of ghrelin through GABAB receptors using CGP35348 (selective GABAB receptor antagonist). METHODS: Male Wistar rats' hippocampi were bilaterally microinjected with the single dose or 10-day ghrelin (0.3 nmol/µl/side). CGP35348, GABAB receptor antagonist, (12.5 µg/µl/side) or saline injected into the dorsal hippocampus 20 minutes before ghrelin administration. Thirty min after ghrelin microinjection, a single convulsive dose of pentylenetetrazole (PTZ) (50 mg/kg) was injected intraperitoneally (i.p). Afterwards, seizure duration and total seizure score (TSS) were assessed for 30 minutes in all animals. RESULTS: Our results demonstrated that acute and chronic intrahippocampal (i.h.) injection of ghrelin could significantly (p<0.001) attenuate the severity of seizures. Ghrelin 0.3 nmol/µl/side decreased duration of seizure significantly both in acute (p<0.001) and chronic (p<0.01) injections. The ghrelin antiepileptic effect was completely antagonized by GABAB blockade. The suppression of both duration and TSS induced by ghrelin in hippocampus was significantly (p<0.001) blocked by CGP35348 in PTZ-induced seizures. CONCLUSION: In summary, our findings suggest that GABAB receptors may mediate the antiepileptic action of ghrelin in the hippocampus. Therefore, it is possible to speculate that ghrelin acts in the hippocampus to modulate seizures via GABA.