Physiology and Pharmacology
Volume:16 Issue: 2, 2012

Oxidative stress is one of the important pathologic factors involved in the pathogenesis of neurodegenerative diseases. Antioxidants as neutralizing agents of free radicals are one of the treatment options for these diseases and antioxidant agents that can pass through blood brain barrier have beneficial effects. In the present research, the antioxidant effect of a new iron nanochelator on the electrophysiological characteristics of neural cells following H2O2– induced oxidative stress was investigated. Intracellular recordings were made under the current clamp condition on F1 cells of Helix aspersa. Effects of oxidant agent, H2O2(1 mM), in the presence of the new iron nanochelator at high (2.63 mM) and low (263 µM) concentrations were assessed on the firing pattern and action potential parameters and were compared to the control condition. Application of H2O2led to a significant decrease in the firing pattern and AP amplitude and an increase in the time to peak compared with control condition. Addition of the antioxidant following H2O2treatment increased these parameters and restored them to the control condition. On the other hand, effects of H2O2 on the electrical activity of cell were modulated when the antioxidant was used earlier. Based on the modulating effects of the new synthesized iron nanochelator on verified action potential parameters in the presence of H2O2, it can be concluded that nanochelator probably exerts its antioxidant effects through the alterations of the function of ion channels.

Astrocytes have an important role in many neurodegenerative diseases. Active astrocytes release inflammatory factors such as NO and ILs. Shikonin, a naphthoquinone pigment of Lithospermum erythrorhizon roots has anti-inflammatory and antitumoral effects. The present study aims to investigate the anti-inflammatory and toxic effects of Shikonin on cultured astrocytes. Two-day-old rat infants'' brains were homogenized after removal of the meninges, and cultured in DMEMF12+10% FBS medium. Ten days later, astrocytes were harvested and re-cultivated for more purifications to 95%, using immunocytochemistry method, and then treated by different concentrations of shikonin (0.1, 0.5, 1, 2.5, 5, 10, 20, 30, 50 and 100μM) for one hour, which was followed by LPS exposure. Viability was measured by MTT assay and NO concentrations were assessed by Griess method, to reveal the inflammation process, after 24 and 48 hours. Shikonin concentrations of 1, 2.5, 5, 10, 20 and 30μM had no anti-inflammatory and cell death effects but at 0.1 and 0.5μM showed a significant anti-inflammatory effect and ability to reduce NO production by astrocytes (p<0.001) and at 100 and 50μM showed a significant cell death effect and NO production reduction (p<0.001). Reduction of NO production might be due to inhibition of release and expression of inflammatory and cell signaling factors such as ILs and iNOS under the shikonin anti-inflammatory effects at concentration around 0.1 and 0.5μM. However, inhibition of NO production by shikonin at 50 and 100μM is probably due to cell death induction.

For some cancer survivors chemotherapy treatment is associated with lasting motor and cognitive impairments, long after treatment cessation. Cisplatin as an anti-neoplastic agent is extremely toxic and can cause severe tissue damage. In the present study, we elucidated alteration in performance of hippocampus- and cerebellum-related behaviors following acute cisplatin treatment in male and female rats. Male and female wistar rats (120) were divided randomly into eight (two controls [saline] and 6 cisplatin) groups. Cerebellum- and hippocampus-related behavioral dysfunction in cisplatin-treated (5, 10 and 15 mg/kg/week for 1 week) rats were analyzed using hippocampus and cerebellum- dependent function tasks (Morris Water Maze, Shuttle box, Rotarod and Open field). Exposure to cisplatin impaired motor coordination in male and female rats in all doses. In open field test, the rearing frequency, total distance moved and velocity of both males and females were dramatically affected by exposure to cisplatin. In Morris water maze test, male and female rats that were trained one week after cisplatin injection showed significant memory deficits compared to the saline-treated rats. Hippocampal and cerebellum functions of male and female rats were profoundly affected by exposure to cisplatin. No sex-difference was observed in the most measured variables.

Ovarian hyper-stimulation is widely used in IVF clinics. The main purpose of this method is to stimulate folliculogenesis and increase the number of oocytes in one cycle. Following ovarian hyper-stimulation, hormonal secretion of the ovary, particularly estradiol and progesterone dramatically increases. Immune cells especially dendritic cells have receptors for the estradiol and progesterone and play an important role in appropriate implantation and successful pregnancy. Increase in estradiol and progesterone concentrations following ovarian stimulation can affect the recruitment and frequency of immune cells particularly dendritic cells. To explore this issue, blood was collected from two groups of pregnant mice (with and without ovarian stimulation) on the seventh day of pregnancy. The amounts of estradiol and progesterone were measured in the sera. The frequency and localization of dendritic cells in spleen and decidua were also investigated by immunohistochemistry. The results of this study showed an increase of progesterone and estradiol concentrations and a decrease of frequency of dendritic cells in hyper-stimulated group compared to the control group. Considering the increase in progesterone and estrogen concentrations after ovarian induction and the presence of receptors for these hormones on dendritic cells, the changes in frequency of dendritic cells could be explained. Regarding the role of dendritic cells in embryo implantation and regulation of maternal immune response, it seems that their changes may decrease the rate of pregnancy success after IVF.

Severe abdominal aortic constriction above the renal arteries induces arterial hypertension above the stenotic site that is the cause of cardiac hypertrophy. Previous studies have shown that high blood pressure induces myocardial oxidative stress with conflicting results. In the present study, we assessed the effects of acute hypertension on the myocardial oxidative stress and its relation with cardiac hypertrophy. Experiments were performed on two groups of rats, sham and hypertensive (n=5 each group). Rats were made acutely hypertensive by aortic constriction above the renal arteries. After 10 days, the carotid artery pressure of rats was recorded and hearts were removed. Following tissue homogenization, superoxide dismutase (SOD) and catalase (CAT) activities, as well as glutathione (GSH) and malondialdehyde (MDA) levels were determined by biochemical methods in heart tissues. Arterial pressure and cardiac hypertrophy index (heart weight/body weight, g/kg) were increased in hypertensive rats 66% and 74%, respectively. SOD and CAT activity were significantly higher in hypertensive rats (34.42±2.51 and 38.63±4.03 U/mg protein, respectively) compared to sham animals (28.58±0.28 and 23.27±2.13 U/mg protein, respectively). Aortic-banding significantly increased GSH content of myocardium by 47%, and there was not any significant difference in the myocardial MDA between the two groups. The findings of this study indicate that acutely elevated arterial blood pressure induces cardiac hypertrophy concomitant with oxidative stress in rat myocardium. This study also reconfirms that oxidative stress may play an important role in the development of cardiac hypertrophy during hypertension.

Olive leaves have been recommended in the scientific literature and traditional medicine as a cure for the treatment of diabetes and this plant has powerful antioxidants and neuroprotective effects. Here, we studied the possible effects of olive leaf extract (OLE) on motor deficits in diabetic neuropathy. The rotarod treadmill test was used to access motor coordination in streptozotocin-induced diabetic rats. Different doses of OLE (100, 300 and 500 mg/kg, i.g.) were given. Serum glucose and insulin levels were assessed by specific kits. Four weeks after diabetes induction, glucose level was significantly decreased and insulin concentration increased (P<0.001). The rotarod treadmill test showed a marked impairment of the motor coordination of the diabetic animals (P<0.001). The retention time of the diabetic animals was reduced by 61.2% compared to the control animals, whereas treatment with 300 mg/kg OLE increased retention time to 83.6% of the control values. That dose had a moderate lowering effect on serum glucose with no effect on insulin levels. The results suggest that olive leaf extract has protective effects against high glucose-induced motor defects in diabetic rats.

In this study, a non-invasive method based on consecutive ultrasonic image processing is introduced to assess time rate changes of the carotid artery wall displacement, velocity and acceleration in the longitudinal direction. The application of these parameters to discriminate healthy and atherosclerotic arteries was evaluated. Longitudinal displacement rate of common carotid artery wall was extracted with temporal resolution of 33 ms using a block-matching algorithm in three groups of subjects. The 3 groups consisted of 16 healthy men (group 1), as well as 16 men with less than 50% (group 2) and 16 subjects with more than 50% atherosclerotic stenosis in carotid artery (group 3). Differentiating the longitudinal displacement equation resulted in time rate changes of instantaneous velocity and acceleration during three cardiac cycles. Maximum and mean values of displacement and maximum and minimum values of velocity and acceleration were compared among the groups. Maximum longitudinal displacement of the arterial wall was 0.438±0.116, 0.653±0.175 and 1.131±0.376 (mm) in groups 1, 2 and 3, respectively. Results of the statistical analysis (ANOVA), with confidence intervals of 95%, confirmed that there are significant differences (p<0.05) among longitudinal movement, velocity and acceleration of three groups of arteries. In the present study, time rate changes of kinematic parameters of the carotid artery wall motion in the longitudinal direction was evaluated, with temporal resolution of 33 ms. Healthy and atherosclerotic arteries were differentiated using these parameters. Our findings may help understanding the biomechanical behavior of the arteries.

Cholesterol has different effects on memory, and diabetes caused adverse effect on cognition. Since there is not enough evidence regarding the effect of cholesterol on memory of diabetic animals, the effects of cholesterol and simvastatin on the passive avoidance memory of diabetic rat were studied. The study was done on 60 male Wistar rats (180 ± 20g). Diabetes was induced by i.p. injection of 65 mg/kg streptozotocin. The animals in diabetic cholesterol, diabetic simvastatin and diabetic cholesterol-simvastatin groups, were treated by 2% cholesterol in diet, daily gavage of 5 mg/kg simvastatin, and concomitant treatment of cholesterol and simvastatin, respectively. The avoidance memory of the rats of each group was measured using shuttle box apparatus 4 weeks later. Also, the cholesterol level of hippocampus was measured. Diabetes had no effects on working memory, but reduced step through latency time during test session. Treatment by cholesterol, simvastatin and cholesterol-simvastatin improved passive avoidance memory in diabetic rats, especially in cholesterol-simvastatin group compared to non-treated diabetic control group. The cholesterol level of hippocampus increased in diabetic cholesterol-simvastatin group compared to other groups (p<0.05). Administration of cholesterol and simvastatin for four weeks protected the diabetic rats against diabetes-induced cognition impairment, yet their combination produced more improvement. Our data suggest that inhibition of endogenous cholesterol synthesis may improve memory of diabetic rats.

The hippocampus is one for the major centers of learning and memory. Role of the opioid system has been investigated and on the other hand receptors related to this system such as mu-opioid receptors (MOR) are extended in the hippocampus. In this study the effect of Naloxone administration as a mu opioid receptor antagonist on passive avoidance memory in adult male rats was investigated by using shuttle box instrument. In this study 45 male adult Wistar rats at range of 200± 20 were used. They were cannulated after anesthesia and Naloxone 0.5, 1, 1.5 and 2 µg/rat has been injected intrahippocampally after recovery and post training by shuttle box. Then after 90 minute short –term memory and after 24 hours long- term memory were measured posttrainingly. results showed that naloxone0.5, 1, 1.5 and 2µg/rat didn’t affected short – term memory on the other hand according to results of long-term memory showed that Naloxone 0.5 µg/rat didn’t affected memory and Naloxone 1 and 1.5 µg/rat improved memory and Naloxone 2 µg/rat impaired memory. Considering to obtained results it seems that Naloxone affected learning and memory in a dose dependent manner.

Amongst the medications to reduce pain, morphine as an important natural and tramadol as an important synthetic drug have been mostly considered. There are few studies on the comparison of the analgesic effect of these drugs in neonatal and perpubertal periods. Neonate rats (n=49) were randomly divided into three groups. On postnatal days 8-14, one group received saline and the two other groups received tramadol and morphine with increasing doses. On postnatal day 21, each group was divided into subgroups, which received each of morphine, tramadol or saline on postnatal days 22-28 (either for the first time or re-exposure). On postnatal days of 22 and 28, the pain-related behavior was tested by hot plate test. Exposure to morphine significantly increased latency of reaction in hot plate test; chronic morphine administration (p28) had a greater effect compared to single dose morphine administration (p22). Tramadol had no significant effect. Morphine and tramadol significantly increased pain latency in re-exposure. In case of tramadol, this increase was greater for single-dose compared to increasing-dose, while in case of morphine, this effect was greater for increasing-dose compared to single-dose. It seems that analgesic effect of re-exposure to tramadol in perepubertal rats is more than morphine and morphine''s effect in the neonatal has a greater dose-dependency. Changes in the brain systems evolution influenced by exposure to these drugs and different functional mechanisms of morphine and tramadol are probably the basis for these results.