Protective effects of Lithium on Sumatriptan-induced memory impairment in mice

Lithium is a drug used for the treatment of bipolar disorder. It has several mechanisms of action, and recently it is shown that lithium can antagonize the 5-HT1B/1D serotonin receptors. Sumatriptan is a 5- HT1B/1D receptor agonist used for the treatment of cluster headaches and migraine which might cause memory impairment as a potential side effect. In this study, effects of lithium on sumatriptan-induced memory impairment have been determined in a two trial recognition Y-maze and passive avoidance tests. Male mice weighing 25-30 g were divided into several groups randomly. In Y-maze test, effects of lithium (1,5,10,20,40,80 mg/kg) and sumatriptan (1,5,10 mg/kg) were assessed on memory acquisition, then lithium (0.1,1,10 mg/kg) and sumatriptan (1,10 mg/kg) were studied in passive avoidance test. Effects of lithium (1mg/kg) on sumatriptan (10 mg/kg)-induced memory impairment were studied in both of tests. The present study demonstrated that sumatriptan impaired memory in Y-maze and passive avoidance tests (P0.05), but significantly reversed sumatriptan-induced memory impairment in Y-maze and passive avoidance tests (P<0.001, P<0.05, respectively). It is concluded that lithium reverses the sumatriptan-induced memory impairment probably through 5-HT1B/1D receptors antagonism. © 2016 Tehran University of Medical Sciences. All rights reserved

Involvement of Inflammatory Cytokines in Antiarrhythmic Effects of Clofibrate in Ouabain-Induced Arrhythmia in Isolated Rat Atria

Considering the cardioprotective and anti-inflammatory properties of clofibrate, the aim of the present experiment was to investigate the involvement of local and systemic inflammatory cytokines in possible antiarrhythmic effects of clofibrate in ouabain-induced arrhythmia in rats. Rats were orally treated with clofibrate (300 mg/kg), and ouabain (0.56 mg/kg) was administered to animals intraperitoneally. After induction of anesthesia, the atria were isolated and the onset of arrhythmia and asystole was recorded. The levels of inflammatory cytokines in atria were also measured. Clofibrate significantly postponed the onset of arrhythmia and asystole when compared to control group (P � 0.05 and P � 0.01, resp.). While ouabain significantly increased the atrial beating rate in control group (P � 0.05), same treatment did not show similar effect in clofibrate-treated group (P > 0.05). Injection of ouabain significantly increased the atrial and systemic levels of all studied inflammatory cytokines (P � 0.05). Pretreatment with clofibrate could attenuate the ouabain-induced elevation of IL-6 and TNF-α in atria (P � 0.01 and P � 0.05, resp.), as well as ouabain-induced increase in IL-6 in plasma (P � 0.05). Based on our findings, clofibrate may possess antiarrhythmic properties through mitigating the local and systemic inflammatory factors including IL-6 and TNF-α. Copyright © 2016 Somayeh Moradi et al

ANTINOCICEPTIVE PROPERTIES OF HYDRO ALCOHOLIC EXTRACTS OF ANETHUM GRAVEOLENS L. (DILL) SEED AND AERIAL PARTS IN MICE

Chronic pain and its treatment have always posed a significant challenge for medical practitioners and many attempts have been made to reduce and eliminate it, both in past and recent history. Research to discover new effective drugs with excellent safety profiles is ongoing. The aim of this study was to evaluate the suitability of the plant Anethum graveolens (dill) for use as an analgesic drug. Forty-two mice were divided randomly into seven groups (n=6). In the formalin test, the first group received normal saline; the second group, extract of plant seed (300 mg/kg); the third group, extract of plant crops (300 mg/kg) and the forth group received morphine (1 mg/kg). For the hot plate test, the first group received normal saline; the second group, extract of plant seed (300 mg/kg) and the third group received extract of plant crops (300 mg/kg). All injections consisted of 0.5 ml given intraperitoneally. In the early phase of formalin test, the animals treated with seed and crop extracts did not show analgesic effects compared to control group (P=0.386, P=0.284 respectively). In contrast, in the late phase of formalin test, seed and crop extracts significantly decreased indications of pain compared to the saline group with seed extracts showing stronger analgesic effects (P=0.004, P=0.023 respectively). In the hot plate test, crop and seed extracts showed hyperalgesic properties. This effect was stronger in animals treated with crop extracts as compared to seed extracts. These findings indicate that Anethum graveolens can reduce inflammatory pain, probably by inhibiting inflammatory mediators. In contrast, this plant has no analgesic effects on spinal nociception and conversely may exacerbate it. This study provides a basis for the use of Anethum graveolens extracts in popular folk medicine, but further studies are necessary to elucidate the mechanism of its analgesic actions

The role of opioid and nitrergic systems in dual modulation of seizure susceptibility

Epilepsy is a chronic disorder presented by recurrent episodes of seizures and affect worldwide individuals. The underlying mechanism of seizure is still elusive. Hence, there is still a need to determine the contribution of various systems in neurobiology and treatment of seizure. Evidence shows that opioid and nitrergic systems within the brain interact to modulate various physiological and pathological conditions including memory, pain, reward, addiction, depression, and seizure. Various studies revealed that diverse dose of opioids such as morphine has dual modulation in seizure susceptibility. For instance, it is reported that morphine at lower doses (0.5, 1, and 3 mg/kg) exerts an anticonvulsant effect in experimental seizure models, whereas at higher doses (15, 30, and 60 mg/kg) it could exacerbate the seizure. Similarly, nitrergic system has also been observed to possess dual effects in modulating the seizure threshold. Therefore, understanding of opioidergic and nitrergic systems interaction in seizure seems important to achieve the successful goal of seizure management. This review aimed to clarify and provide insight into how opioidergic and nitrergic systems interact in brain and mediate seizure behavior. © 2020 UNIV CARLOSIII MADRID. All rights reserved

Cromakalim, a potassium channel opener, ameliorates the organophosphate and carbamate-induced seizure in mice

Organophosphates (OPs) and carbamates are acetylcholine esterase inhibitors (AChEIs), which can cause seizure and lethality. Anticonvulsant properties of potassium channel openers including cromakalim have been determined in previous studies. In the present experiment, the possible effect of cromakalim on the convulsion and death induced by OPs and carbamates was studied in mice. Dichlorvos (an OP, 50 mg/kg) and physostigmine (a carbamate, 2 mg/kg) were used to induce seizure in animals. Cromakalim at doses of 0.1, 10, and 30 µg/kg was injected 30 min before dichlorvos and physostigmine, and 5 min before glibenclamide (a potassium channel blocker, 1 mg/kg) administration. All injections were performed intraperitoneally. After drugs administration, the onset of convulsion, death, the severity of seizure, and rate of mortality were investigated. Results revealed that both dichlorvos and physostigmine induced seizure activity and lethality in 100 of the animals. Cromakalim at doses of 0.1, 10, and 30 µg/kg significantly increased the latency of both seizure and death (P&lt;0.05). Also, cromakalim decreased the mortality rate induced by dichlorvos and physostigmine (P&lt;0.05). On the other hand, glibenclamide blocked all aspects of the anticonvulsant effect of cromakalim (P&lt;0.05). This study revealed for the first time that cromakalim (a KATP channel opener) diminishes the seizure and death induced by dichlorvos and physostigmine in mice, and introduces a new aspect to manage the patients who suffer from OPs/carbamates-induced seizure. © 2018 Tehran University of Medical Sciences. All rights reserved

Cromakalim, a potassium channel opener, ameliorates the organophosphate and carbamate-induced seizure in mice

Organophosphates (OPs) and carbamates are acetylcholine esterase inhibitors (AChEIs), which can cause seizure and lethality. Anticonvulsant properties of potassium channel openers including cromakalim have been determined in previous studies. In the present experiment, the possible effect of cromakalim on the convulsion and death induced by OPs and carbamates was studied in mice. Dichlorvos (an OP, 50 mg/kg) and physostigmine (a carbamate, 2 mg/kg) were used to induce seizure in animals. Cromakalim at doses of 0.1, 10, and 30 µg/kg was injected 30 min before dichlorvos and physostigmine, and 5 min before glibenclamide (a potassium channel blocker, 1 mg/kg) administration. All injections were performed intraperitoneally. After drugs administration, the onset of convulsion, death, the severity of seizure, and rate of mortality were investigated. Results revealed that both dichlorvos and physostigmine induced seizure activity and lethality in 100 of the animals. Cromakalim at doses of 0.1, 10, and 30 µg/kg significantly increased the latency of both seizure and death (P&lt;0.05). Also, cromakalim decreased the mortality rate induced by dichlorvos and physostigmine (P&lt;0.05). On the other hand, glibenclamide blocked all aspects of the anticonvulsant effect of cromakalim (P&lt;0.05). This study revealed for the first time that cromakalim (a KATP channel opener) diminishes the seizure and death induced by dichlorvos and physostigmine in mice, and introduces a new aspect to manage the patients who suffer from OPs/carbamates-induced seizure. © 2018 Tehran University of Medical Sciences. All rights reserved

Immunohistochemical evidence for involvement of inflammatory cytokines in anti-arrhythmic effects of rosuvastatin in male rats

Introduction: Considering the cardioprotective and anti-inflammatory properties of statins, the aim of the present experiment was to investigate the possible involvement of inflammatory cytokines in anti-arrhythmic effects of rosuvastatin in both in vitro and in vivo experiments in rats. Methods: Three weeks after oral administration of either of rosuvastatin or vehicle, the atria were removed and after incubation with ouabain, time of onset of arrhythmia and asystole were recorded. We also used immunohistochemistry technique to identify the differentially expressed proteins interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α in atria. Results: Rosuvastatin significantly postponed the onset of arrhythmia compared to vehicle-treated group. Injection of ouabain increased the atrial expression of IL-1β, IL-6 and TNF-α proteins, while pretreatment of rats with rosuvastatin could significantly attenuate them. Conclusion: Our data suggest that rosuvastatin exerts anti-arrhythmic properties at least in part through modulation of inflammatory cytokines. 10.32598/ppj.24.2.60

Cardiac chronotropic hypo-responsiveness and atrial fibrosis in rats chronically treated with lithium

Lithium is a widely used mood-stabilizing agent; however, it causes a variety of cardiovascular side effects including sinus node dysfunction. In this study we explored the potential adverse effects of lithium on cardiac chronotropic responsiveness, atrial tissue histology and gene expression in rats that were chronically treated with therapeutic doses of lithium. Male Wistar albino rats were given lithium chloride (2.5 g/kg) orally for 2 or 3 months. Following treatment, the atria were isolated and spontaneously beating rate and chronotropic responsiveness to β-adrenergic stimulation was evaluated in an organ bath. Development of cardiac fibrosis was examined by histological methods. The expression of atrial Col1a1 (collagen I, alpha 1) and β-arrestin2 was also assessed using quantitative RT-PCR. Treatment with lithium induced a significant hypo-responsiveness to adrenergic stimulation (P < 0.001) and caused fibrosis in the atrial tissue of treated rats. In addition, the expression of atrial Col1a1 mRNA was significantly increased in atrial tissues of lithium-treated animals, while β-arrestin2 mRNA expression did not show a significant difference compared with control animals. Altogether, these findings indicate that cardiac chronotropic hypo responsiveness and associated cardiac fibrosis are side effects of chronic lithium treatment. Moreover, it seems that lithium treatment does not influence β-arrestin2 mRNA expressio

Involvement of the monoaminergic system in the antidepressant-like effect of the crude extract of Mentha piperita (Lamiaceae) in the forced swimming test in mice

The aim of the present study was to investigate the involvement of the monoaminergic system in antidepressant-like effects of a characterized ethanolic extract of Mentha piperita (MP) in the forced swimming test (FST) in male mice. The animals were intraperitoneally (i.p.) treated with the MP extract (50�400 mg/kg) one hour before FST. To examine the involvement of the monoaminergic system in the antidepressant-like effect of MP, receptor antagonists were administrated fifteen minutes prior to the MP extract treatment (400 mg/kg, i.p) to mice and after one hour the FST was carried out. The MP extract (200 and 400 mg/kg, i.p.) showed a significant antidepressant-like effect (P < 0.001), in the FST, but it did not change the spontaneous locomotor activities in the open-field test. Pretreatment of animals with SCH23390, sulpiride, haloperidol, prazosin, yohimbine, WAY100135, ketanserin, and p-chlorophenylalanine (pCPA) reversed the antidepressant-like effect of the MP extract (400 mg/kg, i.p.) in the FST. In addition, the administration of reserpine increased the duration of immobility elicited by the MP extract in animals. Combinations of the MP extract (50 mg/kg, i.p.,) with sub-effective doses of fluoxetine (5 mg/kg, i.p.) or imipramine (5 mg/kg, i.p.) potentiated the antidepressant-like response. The ethanolic extract of MP exerts antidepressant-like effects, which might be mediated through dopaminergic (D1 and D2), noradrenergic (α1 and α2), and serotonergic (5-HT1A, 5-HT2A) receptors. These first results including the potentiating effect of the MP extract on fluoxetine and imipramine suggest further investigations of MP for the management of depression. © 2017 Elsevier Gmb

POISONED BAITS: A RISING CONCERN FOR ANIMAL HEALTH

Objective: In Europe, malicious animal poisonings are nowadays of concern for both the animal and human health. Focusing on Italy, this problem has been afforded at the beginning of this century. In this frame, a law ruling-banning the preparation, possess, and employment of poisoned baits, was issued in 2001. Poisoned bait is a special threat to dogs and cats but it also kills birds of prey such as owls, kites and eagles, as well as foxes and badgers. The present study reports an overview on the different types of poisoned “hand made” baits found in 10 years of toxicological analysis. Materials & Methods: Data for this retrospective study were taken from 508 pesticide based baits analyses ranging from January 1999 to December 2009. The presence or absence of a suspected pesticide in baits was investigated by validated laboratory methods using a solid-phase or liquid-liquid extraction followed by separation and characterization by chromatographic techniques. The analyses were carried out for organophosphorus and carbamate pesticides (CI), anticoagulant rodenticides (AR), zinc phosphide (ZP), strychnine (ST) and metaldehyde (MT). In the instance the bait was not positive for the above mentioned toxics, the sample underwent screening analysis in GC-MS. Results & Conclusion: The baits found positive have been classified in 6 different: 1) baits prepared with discard or out of date food. Miscellaneous baits belong to this class and are the most frequent (n° 362, CI 52%; AR 19%; ZP 11%, ST 9%, MT 8%, other [OT] 1%). 2) laborious and original particular baits. This class groups baits that requested particular work and time in preparation, making them original (n° 85, CI 49%; AR 10%; ZP 21%, ST 2%, MT 12%, OT 4%). 3) baits containing more than one toxic substance. These baits are usually the most harmful for the animals (n° 39, CI 65%; AR 59%; ZP 20%; ST 35%; MT 12%; OT 9%). 4) baits containing non toxic material. The final intent to kill the animals is unfortunately well pursued by these baits, and for this reason this class has been inserted in the study (n° 15). 5) baits prepared with non food material. This group is seldom used (n=6, CI 50%; ST 50%), but according to officer’s reports it is a method apparently used from gypsies or other unscrupulous people to kill the guard dogs. 6) in vivo baits. This class had only a case reported