Effects of extremely low frequency magnetic field on the development of tolerance to the analgesic effect of morphine in rats.

This study examined the effects of low frequency magnetic field (MF) on tolerance to analgesic effect of morphine in rats. Rats were made tolerant to morphine by injecting morphine (10 mg/kg, s) once daily for 8 consecutive days. Rats were simultaneously exposed to an MF (50 Hz at 1, 50, and 100 µT for 30 min) before, immediately, or 30 min after injection of morphine, and also exposed to a 0.5, 6, 12, and 30 Hz at 100 µT for 30 min before injection of morphine. The percentage of maximum possible effect of morphine (% MPE) was measured on the 1st, 4th, and 8th days by hot plate test. We observed that MF radiation (50 Hz at 1 µT and 30 Hz at 100 µT) immediately before and MF radiation (50 Hz at 100 µT) after morphine injection prevented the development of morphine tolerance compared to control. Also, we found that exposure to MF (50 Hz at 1, 50, and 100 µT) 30 min after injection of morphine failed to maintain the analgesic effect of morphine. Our results showed that exposure to low frequency electromagnetic field (30 and 50 Hz) immediately before or after the injection of morphine may be a potential method for treating the development of morphine tolerance in rats. Bioelectromagnetics. 38:618-625, 2017. © 2017 Wiley Periodicals, Inc.

Prangos ferulacea (L.) ameliorates behavioral alterations, hippocampal oxidative stress markers, and apoptotic deficits in a rat model of autism induced by valproic acid.

BACKGROUND: Prenatal exposure to valproic acid (VPA) may enhance the risk of autism spectrum disorder (ASD) in children. This study investigated the effect of Prangos ferulacea (L.) on behavioral alterations, hippocampal oxidative stress markers, and apoptotic deficits in a rat model of autism induced by valproic acid. METHODS: Pregnant rats received VPA (600 mg/kg, intraperitoneally [i.p.]) or saline on gestational day 12.5 (E 12.5). Starting from the 30th postnatal day (PND 30), the pups were i.p. administered Prangos ferulacea (PF, 100 and 200 mg/kg), or the vehicle, daily until PND 58. On PND 30 and 58, various behavioral tasks were used to evaluate pups, including the open field, elevated plus-maze, hot-plate, and rotarod test. On PND 65, the animals were euthanized, and their brains were removed for histopathological and biochemical assay. RESULTS: Prenatal exposure to VPA caused significant behavioral changes in the offspring, reversed by administering an extract of Prangos ferulacea (L.). Additionally, prenatal VPA administration resulted in increased levels of malondialdehyde and deficits in antioxidant enzyme activities in the hippocampus, including catalase and glutathione, ameliorated by PF. Likewise, postnatal treatment with PF improved VPA-induced dysregulation of Bax and Blc2 in the hippocampus and reduced neuronal death in CA1, CA3, and dentate gyrus. CONCLUSION: The findings of this study suggest that postnatal administration of PF can prevent VPA-induced ASD-like behaviors by exhibiting antiapoptotic and antioxidant properties. Therefore, PF may have the potential as an adjunct in the management of ASD.

Antinociceptive effects of hydroalcoholic extract of Thymus vulgaris.

Previous investigation has shown that Thymus Vulgaris (TV) modulates pain. The aim of this work was to examine the role of TV on acute and chronic pain and compares its effect with dexamethasone (DEX) and stress (ST) by using hot plate, tail flick and formalin tests in mice. In this study male albino mice (25-30 g.) in 21 groups (n=147) were used. TV (100, 500 and 1000 mg/kg), DEX (0.5, 1 and 2 mg/kg) and vehicle (VEH) were injected 30 minutes before pain assessment tests. Stress was applied by 1 min swimming in cold water (18-22 degrees ). Acute and chronic pain was assessed by hot plate, tail flick and formalin tests. For assessment of the role of opioid receptors in antinoceception of TV extract, Naloxon (NAL, 2mg/kg, ip) as opioid receptor antagonist was injected before the injection of the more effective dose (500 mg/kg) of TV extract. Results indicated that TV, DEX and ST have analgesic effects in all tests (P<0.01 in comparison with control group). Above findings showed that TV extract, DEX and ST have modulatory effects on acute and chronic pain. Further research is required to determine the mechanisms by which TV extract has an inhibitory effect on pain sensation.

Peripheral injection of dexamethasone modulates anxiety related behaviors in mice: an interaction with opioidergic neurons.

Stress and anxiety initiates a cascade of biochemical and endocrine event which results in behavioral and electrophysiological effects in both animals and humans. In this study, we investigated the effects of dexamethasone (DEX), as a synthetic glucocorticoid, and its interaction with opioidergic system on anxiety related behavior in mice. Young adult male mice were used in this study. A standard elevated plus-maze was used to determine anxiety levels in animal. Different doses of DEX (0.1, 0.5, 1, 2 and 10 mg/kg, SC) or vehicle was injected 30 min before of evaluation. Naloxone (1 and 2 mg/kg, IP) was injected 5 min before the DEX (0.5 and 1 mg/kg) administration. Results indicated that DEX at doses of 0.5 and 1 reduced and in dose of 10 mg/kg increased anxiety related behaviors significantly (P<0.05 in all cases). Also pretreatment of naloxone at doses of 1 and 2 mg/kg attenuated the effects of lower doses of DEX on anxiety related behaviors. Finding above indicated that peripheral administration of glucocorticoids induces biphasic effects on anxiety related behaviors: anxiolytic effects in lower doses and anxiogenic effects in a high dose. Data also revealed an involvement of opioidergic system in anxiolytic effects of glucocorticoids.

Effects of ethanol extract of propolis on histopathological changes and anti-oxidant defense of kidney in a rat model for type 1 diabetes mellitus.

AIMS/INTRODUCTION: Oxidative stress has a key role in the pathogenesis of diabetes. Propolis and its constituents have a wide range of medicinal properties against oxidative stress. In the present study, we evaluated the anti-oxidant effects of ethanolic extracts of propolis on kidneys in diabetes mellitus rats. MATERIALS AND METHODS: A total of 40 male Wistar rats were randomly divided into the following five groups: control, diabetes mellitus, diabetes mellitus with vehicle treatment, diabetes mellitus with propolis treatment (100 mg/kg) and diabetes mellitus with propolis treatment (200 mg/kg). Diabetes mellitus in rats was induced by intraperitoneal injection of streptozotocin (60 mg/kg). Diabetic groups were treated with vehicle or ethanolic extracts of Iranian propolis for 6 weeks. Serum concentration of malondialdehyde, superoxide dismutase and glutathione peroxidase were measured. RESULTS: The results showed that Iranian propolis significantly inhibited bodyweight loss in diabetes mellitus rats. The propolis extracts significantly reduced serum glucose levels and kidney weight in diabetes mellitus rats (P < 0.001). Furthermore, propolis extracts significantly reduced the malondialdehyde content, and increased the activity of superoxide dismutase and glutathione peroxidase (P < 0.001) along with the total anti-oxidant activity in the kidney tissue of diabetes mellitus rats. In the kidneys of the diabetes mellitus and vehicle group, the glomerular basement membrane thickness and glomerular area were significantly increased. Treatment of diabetes mellitus rats with the propolis extract significantly reduced the glomerular basement membrane thickness and glomerular area. CONCLUSIONS: The present study results showed that the Iranian propolis extract could enhance the anti-oxidant levels and histopathological changes in the kidneys of rats. The final results showed that most of the favorable effects of propolis are mediated by a reduction of blood glucose levels in diabetic animals.

Opiate System Mediate the Antinociceptive Effects of Coriandrum sativum in Mice.

Our previous study showed that Coriandrum sativum (CS) has antinociceptive effects, but the mechanisms that mediate this effect are not clear. The present study was designed to test the role of opiate system in the antinociceptive effects of CS on acute and chronic pain in mice using Hot Plate (HP), Tail Flick (TF) and Formalin (FT) tests and also to compare its effect with dexamethasone (DEX) and stress (ST). Young adult male albino mice (25-30 g) in 33 groups (n = 8 in each group) were used in this study. CS (125 250, 500 and 1000 mg/Kg IP), DEX (0.5, 1 and 2 mg/Kg IP), vehicle (VEH) or swim stress were used 30 min before the pain evaluation tests. Acute and chronic pain was assessed by HP, TF and FT models. In addition, Naloxone (NAL, 2 mg/Kg, IP) was injected 15 min before the CS extract administration in order to assess the role of opiate system in the antinociception of CS. Results indicated that CS, DEX and ST have analgesic effects (p < 0.01) in comparison with the control group and higher dose of CS was more effective (p < 0.001). Besides, pretreatment of NAL modulates the antinociceptive effects of CS in all models (p < 0.001). The above findings showed that CS, DEX and ST have modulator effects on pain. These findings further indicate that the CS extract has more analgesic effects than DEX and ST and also provides the evidence for the existence of an interaction between antinociceptive effects of CS and opiate system.

Evaluation of topical Matricaria chamomilla extract activity on linear incisional wound healing in albino rats.

In this investigation, the effect of Matricaria chamomilla extract on linear incisional wound healing was studied. Thirty male Wistar rats were subjected to a linear 3 cm incision made over the skin of the back. The animals were randomly divided into three experimental groups, as control, olive oil, and treatment. Control group did not receive any drug or cold cream. Olive oil group received topical olive oil once a day from beginning of experiments to complete wound closure. Treatment group were treated topically by M. chamomilla extract dissolved in olive oil at the same time. For computing the percentage of wound healing, the area of the wound measured at the beginning of experiments and the next 2, 5, 8, 11, 14, 17, and 20 days. The percentage of wound healing was calculated by Walker formula after measurement of the wound area. Results showed that there were statistically significant differences between treatment and olive oil animals (p < 0.05) in most of the days. We conclude that the extract of M. chamomilla administered topically has wound healing potential in linear incisional wound model in rats.

Verapamil enhances acute stress or glucocorticoid-induced deficits in retrieval of long-term memory in rats.

This study was designed to investigate an interaction between acute restraint stress and corticosterone with verapamil, a blocker of L-type voltage-dependent calcium (VDC) channels on retrieval of long-term memory. Young adult male rats were trained in one trial inhibitory avoidance task (0.5 mA, 3 s footshock). On retention test given 48 h after training, the latency to re-enter dark compartment of the apparatus was recorded. In Experiment 1, verapamil pretreatment (5, 10, or 20 mg/kg) enhanced the impairing effects of acute stress (which was applied for 10 min in a Plexiglass tube 30 min before the retention test) on memory retrieval. The applied stress increased circulating corticosterone levels as assessed immediately after the retention test, indicating that stress-induced impairment of memory retrieval is mediated, in part, by increased plasma levels of glucocorticoids. Verapamil did not change this response. In Experiment 2, pretreatment of an intermediate dose of verapamil also enhanced corticosterone-induced impairment of memory retrieval. In Experiments 3 and 4, acute stress or corticosterone did not change motor activity with or without prior treatment of verapamil, suggesting that stress or glucocorticoid-induced impairment of memory retrieval is not due to any gross disturbances in motor performance of animals. These findings indicate that blockade of L-type VDC channels enhances stress or glucocorticoid-induced impairment of memory retrieval, and provide evidence for the existence of an interaction between glucocorticoids and L-type VDC channels on memory retrieval.

Antispasmodic effect of hydroalcoholic extract of Thymus vulgaris on the guinea-pig ileum.

The effects of Thymus vulgaris hydroalcoholic extract on the contractile responses of the isolated guinea-pig ileum were investigated. Contraction changes in the terminal ileum of guinea pigs were monitored using a force displacement transducer amplifier connected to a physiograph. Thymus vulgaris extract inhibited the contractile responses in a dose-dependent manner and also decreased the amplitude of peristaltic waves. It is concluded that T. vulgaris has an antispasmodic action on guinea pig ileum by decreasing the amplitudes of the muscle contractions during peristalsis. The EC50 was calculated as 1.7 mg mL(-1). In guinea-pig ileum the extract led to an antispasmodic effect, possibly by affecting the anticholinergic and serotoninergic pathways.

Acute exposure to a 50 Hz magnetic field impairs consolidation of spatial memory in rats.

This study was planned to evaluate the effect of an exposure to magnetic fields on consolidation and retrieval of hippocampus dependent spatial memory using a water maze. In Experiments 1 and 2, rats were trained in a hidden version (spatial) of water maze task with two blocks of four trials. The retention of spatial memory was evaluated 48 h later. Exposure to a 50 Hz 8 mT, but not 2 mT magnetic fields for 20 min immediately after training impaired retention performance. The same time exposure shortly before retention testing had no effect. In Experiment 3, rats were trained in a cued version of water maze with two blocks of four trials. Exposure to magnetic field at 8 mT for 20 min immediately after training did not impair retention performance. These findings indicate that acute exposure to a 50 Hz magnetic field at 8 mT for short time can impair consolidation of spatial memory.

Antimotility effect of hydroalcoholic extract of yarrow (Achillea millefolium) on the guinea-pig ileum.

The use of medicinal herbs among the general population gives rise to the possibility of therapeutic or toxic effects in patients that use these plants. The effects of Achillea millefolium hydroalcoholic extract on the contractile responses of the isolated guinea-pig ileum were investigated. The effect of the Achillea millefolium extracts at five concentrations ranging form 0.05 to 5 mg mL(-1) was tested. The terminal ileum was removed. Segments were fixed in an organ bath containing in Tyrode solution. Contraction changes in the tissues were monitored using force displacement transducer amplifier connected to physiograph. Each segment served as its own control. Achillea millefolium inhibited the contractile response in a dose-dependent manner. The 50% effective concentration values (EC50) were calculated, which was 1.5 mg mL(-1). Regression analysis had shown that with increasing in extract concentration the effect of extract was increased. The coefficient of extract dose was 0.031 mg. Present results demonstrate that extract prepared from the plant of Achillea millefolium inhibited electrical induced contractions of the guinea-pig ileum when tested in vitro. This effect is dose dependent and reversible.