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

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

Histopathological evaluation of the effectiveness of glycyrrhizic acid as a radioprotector against the development of radiation-induced lung fibrosis

Background: Radiotherapy of the thorax often causes lung inflammation leading to fibrosis. Objectives: The aim of this study was to investigate whether the use of glycyrrhizic acid (GLA) could improve the development of lung fibrosis in irradiated animals. Materials and Methods: Wistar rats were divided into four groups. Group A rats received thoracic irradiation. Rats in group B received GLA and irradiation. Group C received GLA and no irradiation. Group D received no GLA and irradiation. GLA was administered at a dose of 4 mg/kg body weight using an intraperitoneal injection one hour before thoracic irradiation. Radiation therapy was delivered on a Cobalt-60 unit using a single fraction of 16 Gy. The animals were sacrificed at 32 weeks following thoracic irradiation. The lungs were dissected and blind histopathological evaluation was performed. Results: Histopathologically, a decrease (statistically not significant) in the thickening of alveolar or bronchial wall, formation of fibrous bands, and superimposed collagen were noted in the animals in group B as compared to the animals in group A. Conclusion: In this experimental study, administration of GLA one hour before thoracic irradiation may be a protective agent against radiation-induced fibrosis in animals and this model could be used in future studies. © 2016, Tehran University of Medical Sciences and Iranian Society of Radiology

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

In vivo analgesic and anti-inflammatory effects of the essential oil from Artemisia sieberi fruit

Background and objectives: Drugs with analgesic properties such as opioids and NSAIDs have not been effective in all cases, because of their low potency and side effects. As a result, looking for other alternatives is necessary. Plants are important sources of new phytochemicals that possess significant therapeutic effects. Regarding the traditional use of Artemisia sieberi fruit as a natural painkiller and anti-inflammatory agent and the high content of essential oil in the fruits, we were prompted to investigate the anti-inflammatory and analgesic activities of A. sieberi fruits oil. Methods: Artemisia sieberi fruits essential oil was extracted by hydrodistillation method. The analgesic and anti-inflammatory activities of the oil were studied by formalin and carrageenan tests, respectively at the doses of 0.2, 0.4 and 0.8 mg/kg for the experimental animals. Control group received sweet almond oil as the vehicle and standard groups received morphine (2 mg/kg) and indomethacin (5 mg/kg) for the formalin and carrageenan tests respectively. Results: All doses of A. sieberi fruits essential oil induced antinociceptive activity during the second phase of the formalin test but the maximum effect was observed at the dose of 0.8 mg/kg. In carrageenan test all the experimental doses of theoil significantly reduced the inflammation (

ROLE OF CHOLINERGIC SYSTEM ON THE CONSTRUCTION OF MEMORY AND ITS INTERACTION WITH DOPAMINERGIC SYSTEM

The central cholinergic system has been associated with cognitive function and memory and acetylcholine plays an important role during the early stages of memory consolidation. In this study, after training mice were tested with one way active avoidance procedure and retention were tested at 4, 8, 12, 16 and 24 hours of training and compared with non-shocked mice, in which it took 24 hours, a suitable time for retention test. Low dose administration of arecoline and physostigmine pre-training, immediate post-training and before retrieval showed that muscarinic agonist arecoline can potentiated memory in post trained and retrieval phases and reversible cholinesterase inhibitor physostigmine potentiated memory only in retrieval phase. Scopolamine disrupted acetylcholine potentiation only in retrieval phase. In the second part of this study, the effect of dopaminergic system was investigated. Low dose of apomorphine and D2 agonist bromocriptine potentiated memory when administered immediately post-training, and D2 antagonist sulpiride impaired memory. When the cholinergic system was blocked by scopolamine immediately post-training, apomorphine and bromocriptine potentiated memory and sulpiride impaired it. In conclusion, these results suggest that, cholinergic system in retrieval phase is very critical and there was no interaction between the two systems in the post-training phase