The effects of subtoxic dose of acetaminophen combined with exercise on the liver of rats.

Regular physical exercise is beneficial to the body. Acute exercise causes oxidant stress in many tissues including the liver by creating an unbalanced status between oxidant and antioxidant levels. Analgesic drugs are commonly consumed to reduce the pain after exercise. Acetaminophen (APAP), commonly used as an over-the-counter analgesic, can cause hepatotoxicity. The aim of this study was to investigate the effect and underlying mechanisms of APAP at subtoxic dose, which is given after the acute and exhaustive exercise on the rat livers. Male Wistar rats weighing 200-250 g were divided into 6 groups each consisting of 7 rats/group; Control, APAP (250 mg/kg, ip), Acute Exercise (AEx), Acute Exhaustive Exercise (AEEx), Acute Exercise and APAP (AEx+APAP) and Acute Exhaustive Exercise and APAP (AEEx+APAP) groups. Rats were exercised at moderate intensity or exhaustive on the treadmill and then received APAP. Tissue MDA levels were significantly increased in AEEx, AEx+APAP and AEEx+APAP groups compared with the control. There was no significant difference in GSH levels between groups. Tissue Sirtuin1 (Sirt1) levels of APAP, AEx and AEEx groups were significantly less than control. There was no significant difference between groups in VEGF levels. Liver damage score was significantly higher in all groups compared with control group. As a result, this study shows that subtoxic dose of APAP treatment alone or in combination with acute or exhaustive treadmill exercise can cause oxidative liver damage by affecting Sirt1 levels and without affecting VEGF levels.

The effect of exercise on anxiety- and depression-like behavior of aged rats.

We investigated the effects of exercise in multiple sessions on anxiety- and depression-like behavior during aging, and the role of serotonin and serotonin 1A receptors in this process. Both 24-month-old (aged) and 6-month-old (adult) female rats were divided into five groups; aged control, adult control, aged + serotonin re-uptake inhibitors (SSRIs), aged + exercise, and aged + SSRIs + exercise. After exercise, all groups were evaluated using the open field arena, elevated plus maze and forced swim tests. We assessed serum corticosterone levels; number of amygdala, hippocampus and prefrontal cortex cells; tissue serotonin and serotonin 1A (5-HT1A) levels. In the open field test, aged rats exhibited a significant increase in locomotor activity compared to the SSRIs and SSRIs + exercise groups. During the elevated plus maze test, aged rats were observed less frequently in the open arms of assembly compared to adults. The duration increased in the exercise group and remained unchanged in the SSRIs group. In the forced swim test, the aged rats were more immobile compared to adults; no change was observed in the immobility time between these groups. The tissue serotonin levels in amygdala and hippocampus were higher in SSRIs + exercise group compared to the aged, exercised and SSRIs groups. The number of cells in the hippocampus, prefrontal cortex and amygdala decreased in the aged group compared to adult rats; increased numbers of cell were observed in exercise, SSRIs and SSRIs + exercise groups compared to aged rats. Exercise in multiple sessions may increase the number of cells in the hippocampus, prefrontal cortex and amygdala, which may reduce senile anxiety and depression. Also, serotonin and serotonin 1A receptors may play role in depression-like behavior.

Dose dependent effects of oxytocin on cognitive defects and anxiety disorders in adult rats following acute infantile maternal deprivation stress.

Maternal deprivation at an early age is a powerful stressor that causes permanent alterations in cognitive and behavioral functions during the later stages of life. We investigated the effects of oxytocin on cognitive defects and anxiety disorders caused by acute infantile maternal deprivation in adult rats. We used 18-day-old Wistar albino rats of both sexes. The experimental groups included control (C), maternally deprived (MD), maternally deprived and treated with 0.02 µg/kg oxytocin (MD-0.02 µg/kg oxy), maternally deprived and treated with 2 µg/kg oxytocin (MD-2 µg/kg oxy). When the rats were 60 days old, the open field (OF) and elevated plus maze (EPM) behavioral tests, and the Morris water maze (MWM) test for spatial learning and memory were performed. In addition, the number of neurons in the hippocampus, prefrontal cortex (PFC) and amygdala were determined using quantitative histology. We also measured vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) levels in the PFC. In both sexes, the MD group failed the learning test and the MD-2 µg/kg oxy group failed in the memory test. The MD-0.02 µg/kg oxy group spent more time in the open arm of the EPM device and their locomotor activities were greater in the OF test. The VEGF and BDNF levels in the PFC were higher in the MD-0.02 µg/kg oxy groups than the other maternally deprived groups (oxytocin ±). The number of PFC neurons was low in all male maternally deprived (oxytocin ±) groups, while the number of amygdala neurons was low in both female and male maternally deprived (oxytocin ±) groups. Male rats were more affected by maternal deprivation; administration of oxytocin had dose-dependent biphasic effects on learning, memory and anxiety.

Effects of voluntary and involuntary exercise on cognitive functions, and VEGF and BDNF levels in adolescent rats.

Regular treadmill running during adolescence improves learning and memory in rats. During adolescence, the baseline level of stress is thought to be greater than during other periods of life. We investigated the effects of voluntary and involuntary exercise on the prefrontal cortex and hippocampus, vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF) levels, and spatial learning, memory and anxiety in adolescent male and female rats. The voluntary exercise group was given free access to a running wheel for 6 weeks. The involuntary exercise group was forced to run on a treadmill for 30 min at 8 m/min 5 days/week for 6 weeks. Improved learning was demonstrated in both exercise groups compared to controls. Neuron density in the CA1 region of the hippocampus, dentate gyrus and prefrontal cortex were increased. Hippocampal VEGF and BDNF levels were increased in both exercise groups compared to controls. In females, anxiety and corticosterone levels were decreased; BDNF and VEGF levels were higher in the voluntary exercise group than in the involuntary exercise group. The adolescent hippocampus is affected favorably by regular exercise. Although no difference was found in anxiety levels as a result of involuntary exercise in males, females showed increased anxiety levels, and decreased VEGF and BDNF levels in the prefrontal cortex after involuntary exercise.

Beneficial effects of arginase inhibition and inhaled l -arginine administration on airway histology in a murine model of chronic asthma

BACKGROUND: Increased arginase activity in the airways induces reduced bioavailability of l -arginine and cause deficiency of bronchodilatating and anti-inflammatory nitric oxide (NO). Therefore, arginine and arginase inhibitors may have therapeutic potential in the treatment of asthma. Using a murine model of asthma, we aimed to investigate the effects of inhaled l -arginine and arginase inhibitor Nω-hydroxy-nor- l -arginine (nor-NOHA) and co-treatment on airway histology of asthmatic lung tissue. METHODS: Forty-two BALB/c mice were divided into six groups: I (control), II (placebo), III, IV, V and VI. All mice except for control group were sensitised by an intraperitoneal injection of ovalbumin with alum adjuvant and then challenged with an aerosol of ovalbumin on three days of the week for eight weeks beginning from the 21st day of the study. Lung histology and bronchoalveolar lavage cell (BAL) counts were evaluated after treatment with inhaled l -arginine, nor-NOHA, l -arginine-nor-NOHA combination, budesonide and placebo. Interleukin (IL)-4 and IL-5 levels are determined in lung homogenates with ELISA. RESULTS: l -Arginine group was similar to budesonide group in lowering all histological parameters. Results of groups treated with nor-NOHA were also similar to budesonide group except for epithelial thickness. The number of eosinophils in BAL decreased significantly in groups receiving study drugs. Decrease was only noted in IL-4 levels in group receiving nor-NOHA. CONCLUSION: We demonstrated that inhaled l -arginine administration alleviated all histological parameters similar to budesonide and treatment with arginase inhibitor improved not all but some of the pathological changes in chronic asthma. Combination therapy had no additive effect on either treatment

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Effects of carbon dioxide exposure on early brain development in rats.

The developing brain is vulnerable to environmental factors. We investigated the effects of air that contained 0.05, 0.1 and 0.3% CO2 on the hippocampus, prefrontal cortex (PFC) and amygdala. We focused on the circuitry involved in the neurobiology of anxiety, spatial learning, memory, and on insulin-like growth factor-1 (IGF-1), which is known to play a role in early brain development in rats. Spatial learning and memory were impaired by exposure to 0.3% CO2 air, while exposure to 0.1 and 0.3% CO2 air elevated blood corticosterone levels, intensified anxiety behavior, increased superoxide dismutase (SOD) enzyme activity and MDA levels in hippocampus and PFC; glutathione peroxidase (GPx) enzyme activity decreased in the PFC with no associated change in the hippocampus. IGF-1 levels were decreased in the blood, PFC and hippocampus by exposure to both 0.1 and 0.3% CO2. In addition, apoptosis was increased, while cell numbers were decreased in the CA1 regions of hippocampus and PFC after 0.3% CO2 air exposure in adolescent rats. A positive correlation was found between the blood IGF-1 level and apoptosis in the PFC. We found that chronic exposure to 0.3% CO2 air decreased IGF-1 levels in the serum, hippocampus and PFC, and increased oxidative stress. These findings were associated with increased anxiety behavior, and impaired memory and learning.

The effects of resveratrol on chronic constriction injury of sciatic nerve in rats.

The aim of this study was to investigate the effects of resveratrol (RVT) in chronic constriction injury (CCI) of sciatic nerve by behavioral, histomorphological and immunohistochemical evaluations in rats. In this study, male Wistar rats were divided into three groups: sham (n=7), CCI+saline (n=7) and CCI+RVT (n=7). After inducing CCI, treatment with 10mg/kg/day of RVT or saline for 14 days was given. Locomotor function was assessed with rota-rod and open field tests. Morphologic alterations of sciatic nerve were assessed histologically by light and electron microscopy. Immunohistochemistry for insulin-like growth factor-1 (IGF-1) were performed. RVT treatment prevented motor impairment and histomorphological alterations caused by chronic constriction injury of sciatic nerve. IGF-1 immunoreactivity was significantly higher in RVT treated group then CCI induced group and positive correlated with morphometric parameters. These results indicate that RVT may reduce CCI induced damage and this effect may be mediated through the restoration of IGF-1 immunoreactivity.

Beneficial effects of arginase inhibition and inhaled L-arginine administration on airway histology in a murine model of chronic asthma.

BACKGROUND: Increased arginase activity in the airways induces reduced bioavailability of L-arginine and cause deficiency of bronchodilatating and anti-inflammatory nitric oxide (NO). Therefore, arginine and arginase inhibitors may have therapeutic potential in the treatment of asthma. Using a murine model of asthma, we aimed to investigate the effects of inhaled L-arginine and arginase inhibitor Nω-hydroxy-nor-L-arginine (nor-NOHA) and co-treatment on airway histology of asthmatic lung tissue. METHODS: Forty-two BALB/c mice were divided into six groups: I (control), II (placebo), III, IV, V and VI. All mice except for control group were sensitised by an intraperitoneal injection of ovalbumin with alum adjuvant and then challenged with an aerosol of ovalbumin on three days of the week for eight weeks beginning from the 21st day of the study. Lung histology and bronchoalveolar lavage cell (BAL) counts were evaluated after treatment with inhaled L-arginine, nor-NOHA, l-arginine-nor-NOHA combination, budesonide and placebo. Interleukin(IL)-4 and IL-5 levels are determined in lung homogenates with ELISA. RESULTS: L-Arginine group was similar to budesonide group in lowering all histological parameters. Results of groups treated with nor-NOHA were also similar to budesonide group except for epithelial thickness. The number of eosinophils in BAL decreased significantly in groups receiving study drugs. Decrease was only noted in IL-4 levels in group receiving nor-NOHA. CONCLUSION: We demonstrated that inhaled l-arginine administration alleviated all histological parameters similar to budesonide and treatment with arginase inhibitor improved not all but some of the pathological changes in chronic asthma. Combination therapy had no additive effect on either treatment.

Anxiety- and depression-like behavior are correlated with leptin and leptin receptor expression in prefrontal cortex of streptozotocin-induced diabetic rats.

Anxiety and depression are common in diabetics. Diabetes also may cause reduced leptin levels in the blood. We investigated the relation between diabetes induced anxiety- and depression-like behavior, and leptin and leptin receptor expression levels in diabetic rats. The anxiety- and depression-like behaviors of rats were assessed 4 weeks after intraperitoneal injection of streptozotocin. Diabetic rats exhibited greater anxiety-like behavior; they spent more time in closed branches of the elevated plus maze test and less time in the center cells of the open field arena. Increased depression-like behavior was observed in diabetic rats using the Porsolt swim test. Prefrontal cortex (PFC), blood leptin levels and PFC neuron numbers were decreased, and leptin receptor expression and apoptosis were increased in diabetic rats. Blood corticosterone levels also were increased in diabetic rats. These results indicate that reduction of leptin up-regulates leptin receptor expression and may affect PFC neurons, which eventually triggers anxiety- and depression-like behaviors in diabetic rats.

Effects of exercise and poor indoor air quality on learning, memory and blood IGF-1 in adolescent mice.

It is known that regular aerobic exercise enhances cognitive functions and increases blood insulin-like growth factor 1 (IGF-1) levels. People living in urban areas spend most of their time indoors and indoor air quality can affect health. We investigated the effects of aerobic exercise in poor and good air quality environments on hippocampus and prefrontal cortex (PFC) neurons, anxiety, and spatial learning and memory in adolescent mice. Poor air quality impaired spatial learning and memory; exercise did not affect learning or memory impairment. Exercise in a good air quality environment improved spatial learning and memory. Poor air quality increased apoptosis in the hippocampus and PFC. Both exercised and sedentary groups living in a poor air quality environment had lower serum IGF-1 levels than those living in a good air quality environment. Living in a poor air quality environment has negative effects on the hippocampus, PFC and blood IGF-1 levels in adolescent mice, but exercise did not alter the negative effects of poor air quality.

Progesterone treatment decreases traumatic brain injury induced anxiety and is correlated with increased serum IGF-1 levels; prefrontal cortex, amygdala, hippocampus neuron density; and reduced serum corticosterone levels in immature rats.

Traumatic brain injury (TBI) may cause neuropsychiatric problems, such as anxiety disorder, that have negative effects on cognitive functions and behavior. We investigated the effects of progesterone on traumatic brain injury induced anxiety in 7-day-old rat pups subjected to contusion injury. Progesterone treatment decreased TBI induced anxiety and serum corticosterone levels, and increased serum IGF-1 levels. Moreover, progesterone treatment increased amygdala, prefrontal cortex and hippocampal neuron density. We found a negative correlation between serum corticosterone levels and anxiety tests, and a positive correlation between serum IGF-1 levels and anxiety tests. In addition, progesterone treatment decreased serum corticosterone compared to the controls and sham. Our results indicate that single dose progesterone may be effective for treating anxiety caused by TBI.

Beneficial effects of erythropoietin on airway histology in a murine model of chronic asthma

Background: Erythropoietin (EPO) is originally defined as a haematopoietic growth factor, but also has anti-inflammatory effects through cytokine modulation. This anti-inflammatory and cytokine modulating effect has not been investigated for the treatment of asthma. We aimed to determine the beneficial effects of erythropoietin on lung histology of murine model of chronic asthma. Methods: Thirty-five BALB/c mice were divided into five groups: I; II; III; IV; and control group. All groups except control group were sensitised and challenged with ovalbumin. Mice with experimentally induced asthma in Group I received saline; Group II EPO 500IU/kg; Group III EPO 1000IU/kg; and Group IV dexamethasone 1mg/kg intraperitoneally once a day in the last five days of the challenge period. Animals were sacrificed 24h after the last administration of study drugs. Histological findings of airways were evaluated by light and electron microscopic examination. Results: All histological parameters of asthma in the group treated with a high dose of EPO (Group III) were significantly ameliorated when compared with the group treated with saline (Group I). In comparison to the group treated with low dose of EPO (Group II) and the group treated with saline (Group I), basement membrane thicknesses and number of mast cells were significantly lower in the group treated with low dose of EPO (Group II). All histological parameters were similar between the group treated with high dose of EPO (Group III) and the group treated with dexamethasone (Group IV) except higher number of mast cells in the group treated with high dose of EPO (Group III). Additionally, the results of all histological parameters in the group treated with high dose of EPO (Group III) were significantly better when compared with the group treated with low dose of EPO (Group II)(AU)

Conclusions: We found that EPO ameliorated histological changes of chronic murine model of asthma. Further studies are needed to evaluate the efficacy of EPO in the treatment of asthma(AU)

Beneficial effects of erythropoietin on airway histology in a murine model of chronic asthma.

BACKGROUND: Erythropoietin (EPO) is originally defined as a haematopoietic growth factor, but also has anti-inflammatory effects through cytokine modulation. This anti-inflammatory and cytokine modulating effect has not been investigated for the treatment of asthma. We aimed to determine the beneficial effects of erythropoietin on lung histology of murine model of chronic asthma. METHODS: Thirty-five BALB/c mice were divided into five groups: I; II; III; IV; and control group. All groups except control group were sensitised and challenged with ovalbumin. Mice with experimentally induced asthma in Group I received saline; Group II EPO 500IU/kg; Group III EPO 1000IU/kg; and Group IV dexamethasone 1mg/kg intraperitoneally once a day in the last five days of the challenge period. Animals were sacrificed 24h after the last administration of study drugs. Histological findings of airways were evaluated by light and electron microscopic examination. RESULTS: All histological parameters of asthma in the group treated with a high dose of EPO (Group III) were significantly ameliorated when compared with the group treated with saline (Group I). In comparison to the group treated with low dose of EPO (Group II) and the group treated with saline (Group I), basement membrane thicknesses and number of mast cells were significantly lower in the group treated with low dose of EPO (Group II). All histological parameters were similar between the group treated with high dose of EPO (Group III) and the group treated with dexamethasone (Group IV) except higher number of mast cells in the group treated with high dose of EPO (Group III). Additionally, the results of all histological parameters in the group treated with high dose of EPO (Group III) were significantly better when compared with the group treated with low dose of EPO (Group II). CONCLUSIONS: We found that EPO ameliorated histological changes of chronic murine model of asthma. Further studies are needed to evaluate the efficacy of EPO in the treatment of asthma.

Fetuses with single umbilical artery: analysis of 45 cases.

OBJECTIVE: The aim of this study was to analyze cases and determine the clinical significance of a prenatally detected single umbilical artery (SUA) in our population. MATERIALS AND METHODS: All second and third trimester sonographic examinations carried out between January 2004 and September 2007 in our perinatology unit were reviewed. The postnatal results of the fetuses with SUA were obtained from the medical records and the patients. RESULTS: From a total of 5,620 pregnant patients who were examined by ultrasound (US) scan between 15-36 weeks, a single umbilical artery was found in 45 cases, representing an incidence of 0.8%. Of these, 20 (45%) also presented with other malformations. There were six neonatal deaths, one fetal demise, and six terminations of pregnancy due to severe malformations in this group. Three cases with associated anomalies underwent surgery and one case required intensive care in the neonatal period. The only cytogenetic abnormality was trisomy 18 in one case. Six of 45 fetuses (13%) with single umbilical arteries had abnormal echocardiographic findings. In two of the fetuses associated anomalies (cleft palate and esophageal atresia) were detected after birth. In pregnancies without associated anomalies no aneuploidy was found and they were completely normal at birth and during the neonatal period. CONCLUSIONS: Scanning the umbilical cord is one of the essential parts of US examination. As the rate of cardiac malformations seen with single umbilical arteries is high, fetal echocardiography should be performed in suspected cases. The newborn should be reexamined immediately after birth due to the possibility of undetected anomalies.

Pregnancy outcome in fetuses with increased nuchal translucency.

OBJECTIVE: The aim of this study was to examine fetal and neonatal outcomes in the setting of nuchal translucency (NT) > or =3 mm at routine first-trimester screening. STUDY DESIGN: A nested case-series study within a retrospective cohort of women screened for Down syndrome at 11-14 weeks of gestation. Crown-rump length, NT values and additional anomalies at first and early second trimesters were recorded. Follow-up information was obtained by a review of medical records and self-report from patients. Adverse outcomes included fetal death and termination of pregnancy due to structural or chromosomal anomalies. RESULT: A total of 1930 pregnant women were screened between 11 and 14 weeks of gestation. The prevalence of increased fetal NT (> or =3 mm) was 1.4% (n=27). Among these, 12 showed increased fetal NT as an isolated finding. In this group, 2 women experienced fetal demise (16%) and 10 delivered healthy babies. In the group with additional abnormalities (n=15), 9 (60%) were found to have chromosomal abnormalities, all of which were terminated. For all cases with increased fetal NT, total incidence of adverse outcome was 62%. CONCLUSION: At first-trimester ultrasonography, a fetal NT > or =3 mm was associated with a high incidence of chromosomal abnormalities in the presence of associated abnormalities. For cases with the increased fetal NT at first-trimester fetal assessment and follow-up is necessary to detect possible adverse outcomes.

Deprenyl and the relationship between its effects on spatial memory, oxidant stress and hippocampal neurons in aged male rats.

Oxidative stress may play a major role in the aging process and associated cognitive decline. Therefore, antioxidant treatment may alleviate age-related impairment in spatial memory. Cognitive impairment could also involve the age-related morphological alterations of the hippocampal formation. The aim of this study was to examine the relationship between the effects of deprenyl, an irreversible monoamine-oxidase B inhibitor, on spatial memory by oxidant stress and on the total number of neurons in the hippocampus CA1 region of aged male rats. In this study, 24-month-old male rats were used. Rats were divided into control and experimental groups which received an injection of deprenyl for 21 days. Learning experiments were performed for six days in the Morris water maze. Spatial learning was significantly better in deprenyl-treated rats compared to saline-treated rats. Deprenyl treatment elicited a significant decrease of lipid peroxidation in the prefrontal cortex, striatum and hippocampus regions and a significant increase of glutathione peroxidase activity in the prefrontal cortex and hippocampus. It was observed that deprenyl had no effect on superoxide dismutase activity. The total number of neurons in the hippocampus CA1 region was significantly higher in the deprenyl group than in the control group. In conclusion, we demonstrated that deprenyl increases spatial memory performance in aged male rats and this increase may be related to suppression of lipid peroxidation and alleviation of the age-related decrease of the number of neurons in the hippocampus. The results of such studies may be useful in pharmacological alleviation of the aging process.

Effects of melatonin on oxidative stress and spatial memory impairment induced by acute ethanol treatment in rats.

Melatonin has recently been suggested as an antioxidant that may protect neurons from oxidative stress. Acute ethanol administration produces both lipid peroxidation as an indicator of oxidative stress in the brain and impairs water-maze performance in spatial learning and memory tasks. The present study investigated the effect of melatonin against ethanol-induced oxidative stress and spatial memory impairment. The Morris water maze was used to evaluate the cognitive functions of rats. Thiobarbituric acid reactive substances (TBARS), which are the indicators of lipid peroxidation, and the activities of antioxidative enzymes (glutathione peroxidase and superoxide dismutase) were measured in the rat hippocampus and prefrontal cortex which form interconnected neural circuits for spatial memory. Acute administration of ethanol significantly increased TBARS levels in the hippocampus. Combined melatonin-ethanol treatment caused a significant increase in glutathione peroxidase activities and a significant decrease of TBARS in the rat hippocampus. In the prefrontal cortex, there was only a significant decrease of TBARS levels in the combined melatonin-ethanol receiving group as compared to the ethanol-treated group. Melatonin did not affect the impairment of spatial memory due to acute ethanol exposure, but melatonin alone had a positive effect on water maze performances. Our study demonstrated that melatonin decreased ethanol-induced lipid peroxidation and increased glutathione peroxidase activity in the rat hippocampus.

Effects of acute footshock stress on antioxidant enzyme activities in the adolescent rat brain.

In a previous study we demonstrated that acute footshock stress increased glutathione peroxidase activity in the prefrontal cortex and striatum of adult male rats. Adolescents may respond differently to stress as life stressors may be greater than at other ages. The present study examined the effects of the acute footshock stress on superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme activities and thiobarbituric acid reactive substances (TBARS) levels in adolescent male and female rat brains. We demonstrated that acute footshock stress increased SOD activity in the prefrontal cortex, and increased GPx activity in the hippocampus in female rats. In males, acute footshock stress increased GPx activity in the prefrontal cortex and hippocampus. Footshock stress did not change TBARS levels. These results indicate a strong role of gender in the response of adolescent subjects to various aspects of stress.