Anti-nociceptive effect of black seed oil on an animal model of chronic constriction injury.

Background and purpose: Traditionally, Nigella sativa L. has been known as a medical intervention to treat numerous diseases. This study aimed at investigating the antihyperalgesic effect of black seed oil (BSO) in an experimental model of neuropathic pain. Experimental approach: Chronic constriction injury (CCI) was performed under anesthesia. The sciatic nerve was ligated with four loose ties. Two separate protocols were used to administer BSO. In chronic treatment, rats were given daily doses of BSO (250, 500, and 1000 mg/kg p.o.) from the 1st day until the 21st post-CCI day. While, in acute treatment, BSO (250, 500, and 1000 mg/kg p.o.) was administered only on the 7th, 14th, and 21st days. CCI and sham groups were given almond oil according to the same schedule. Behavioral scores were determined by evaluation of the paw withdrawal in the plantar, Von Frey, and acetone tests, on the 7th, 14th, and 21st days. Findings/Results: Our results showed that CCI leads to significant allodynia and hyperalgesia in the ipsilateral paw after surgery. Chronic administration of BSO (500 and 1000 mg/kg) obviously attenuated heat hyperalgesia and mechanical allodynia. However, daily administration of BSO did not alter cold allodynia. Nevertheless, when BSO was administered, 30 min before the pain assessment tests, hypersensitivity was not improved in the treated animals. Conclusion and implications: These results demonstrated BSO can inhibit neuropathic pain progression and suggests a potential use of BSO to manage hyperalgesia and allodynia. However, additional research is necessary to approve BSO effectiveness, in neuropathic pain conditions.

Anti-inflammatory and antioxidative effects of thiamin supplements in patients with gestational diabetes mellitus.

OBJECTIVE: The aim of this study was to evaluate the effects of thiamin supplementation on biomarkers of inflammation and oxidative stress in patients with gestational diabetes mellitus (GDM). METHODS: This randomized, double-blind, placebo-controlled trial was conducted among 60 patients with GDM. Patients were randomly allocated into two groups to receive either 100 mg/day thiamin supplements (n = 30) or placebo (n = 30) for 6 weeks. RESULTS: Thiamin supplementation significantly decreased serum high-sensitivity C-reactive protein (hs-CRP) (ß - 0.98 mg/L; 95% CI, -1.54, -0.42; p = .001) and plasma malondialdehyde (MDA) levels (ß - 0.86 µmol/L; 95% CI, -1.15, -0.57; p < .001) when compared with the placebo. In addition, thiamin supplementation downregulated gene expression of tumor necrosis factor-alpha (TNF-α) (p = .002) in peripheral blood mononuclear cells of patients with GDM. Thiamin supplementation did not affect other biomarkers of inflammation and oxidative stress. CONCLUSION: Overall, thiamin supplementation for 6 weeks to patients with GDM significantly reduced hs-CRP and MDA levels, and gene expression of TNF-α, but did not affect other biomarkers of inflammation and oxidative stress. CLINICAL TRIAL REGISTRATION NUMBER: Clinical Trials.govIdentifier no. http://www.irct.ir: IRCT20170513033941N58.

Effect of biotin supplementation on neuropathic pain induced by chronic constriction of the sciatic nerve in the rat.

BACKGROUND AND PURPOSE: Neuropathic pain is one of the most common types of chronic pain that is very difficult to treat. Numerous studies have shown the potential role of vitamins in relieving both hyperalgesia and allodynia. Based on the convincing evidence, this study was designed to evaluate the possible antinociceptive effect of biotin on neuropathic pain in rats. EXPERIMENTAL APPROACH: This study was performed on male Sprague Dawley rats weighing 200-300 g. Neuropathic pain was induced by tying the sciatic nerve. Chronic constriction injury (CCI) of the sciatic nerve resulted in hyperalgesia and allodynia. To measure the thermal hyperalgesia, the plantar test was used. Also to evaluate the cold and mechanical allodynia, acetone test and von Frey test were applied. Biotin (4, 8, and 16 mg/kg) was administered orally as two different treatment regimens, acute and chronic. FINDINGS/RESULTS: Acute oral administration of biotin (4, 8, and 16 mg/kg p.o.) on the 7th, 14th, and 21st postoperative days couldn't reduce pain sensitivity compared to the CCI group. However, following the oral administration of biotin (8 and 16 mg/kg p.o.) from the first day after the surgery until day 21, mechanical allodynia (P < 0.001) and heat hyperalgesia (P < 0.05) significantly relieved. CONCLUSION AND IMPLICATIONS: Our results suggest that biotin can be considered as a potential therapeutic for the treatment of neuropathic pain, and supplementation with this vitamin could reduce the required doses of analgesic drugs. However, further studies are needed to confirm this hypothesis.

Blockade of the orexin 1 receptors in the nucleus accumbens' shell reversed the reduction effect of olanzapine on motivation for positive reinforcers.

Effort-based choice of high reward requires one to decide how much effort to expend for a certain amount of reward. Orexin is a crucial neuropeptide in the physiological aspect especially a variety of affective and cognitive processes. The nucleus accumbens (NAc) is a region of the neural system that serves effort-related high reward choices andthe Orexin 1 receptor (OX1R) is distributed extensively throughout the nucleus accumbens shell (AcbS). Olanzapine (OLZ), a typical antipsychotic drug, has a high affinity to D2 as an antagonist, and also partial agonistic-like action at D2 receptors has been reported. We examined the interaction of OLZ with the orexinergic receptor 1 in AcbS on effort- related high reward choice when two goal arms were different in the amount of accessible reward. The animals had to pass the barrier for receiving a high reward in one arm (HRA) or obtain a low reward in the other arm without any cost. Before surgery, all animals were selecting the HRA on almost every trial.During test days, the rats received local injections of either DMSO 20% /0.5 µl, as vehicle or SB334867 (30, 100, 300 nM/0.5 µl), as selective OX1R antagonist, within the AcbS. Other group received OLZ (32 µM/0.5 µl DMSO20%) / vehicle alone or 5 min after administration of SB334867 (300 nM/0.5 µl). The results showed that administration of OLZ in the AcbS alters rat's preference for high reward. On the other hand, blocked of the OX1R (300 nM/0.5 µl) in this region could reverse the effect of OLZ, however, administration of the OX1R antagonists alone in the AcbS led to decreasing rat's preference for high reward. This result indicates that the orexin-1 antagonist might affect some effects of antipsychotic drugs.

Protective effects of doxepin cream on radiation dermatitis in breast cancer: A single arm double-blind randomized clinical trial.

AIMS: Breast cancer is the most frequently occurring cancer in women. Lumpectomy followed by radiotherapy is suggested to be as effective as a total mastectomy. Radiation-induced dermatitis often occurs as a result of breast radiotherapy. Recent studies suggest that doxepin has promising anti-inflammatory properties. This study was undertaken to evaluate the effects of doxepin therapy on radiation dermatitis. METHODS: A double-blind randomized clinical trial was launched from 2016 to 2017, with a total of 48 patients who had undergone breast-conserving surgery and received postoperative radiation therapy. Radiotherapy was applied 5 days per week for 5 weeks. Adverse dermatological effects were evaluated by a physician at the beginning of the fifth week of radiotherapy and the patients were then randomly assigned (1:1 ratio) to receive either doxepin (5%) or placebo cream for 7 days. RESULTS: There were no significant differences in the dermatitis grade between doxepin and placebo groups at baseline (P > .5). The occurrence of acute dermatitis (grade 2 or higher) was significantly lower with the use of doxepin than with placebo (P ≤ .0001, Zα = 1.96 at 95% confidence interval). CONCLUSION: Doxepin cream prevents dermatitis grade 2 or higher during post-operative breast irradiation. Doxepin cream is easy to use, affordable and prevents pain and irritation.

Evaluation of protective effects of non-selective cannabinoid receptor agonist WIN 55,212-2 against the nitroglycerine-induced acute and chronic animal models of migraine: A mechanistic study.

AIM: Migraine is a neurological debilitating disorder. Previous studies have shown that cannabinoid receptor agonists have analgesic effects in various models of pain. In this study, therefore, we investigated anti-nociceptive effects of WIN 55,212-2, and the role of either CB1 or CB2 receptors in nitroglycerine (NTG)-induced animal model of migraine. METHODS: The present study was conducted on both male and female rats receiving NTG (10 mg/kg, i.p.) to induce acute (single dose of NTG) and chronic (repetitive doses of NTG) models of migraine. Additionally, three groups received WIN 55,212-2 (0.33, 1, 3 mg/kg, i.p.) 45 min before behavioral tests. Additionally, AM251 and AM630 (CB1 and CB2 receptor antagonist, respectively, 1 mg/kg, i.p.) were used to evaluate the possible involvement of CB1 and CB2 receptors during the protective effects of WIN 55,212-2. KEY FINDINGS: We found that NTG (10 mg/kg, i.p.) in both acute and chronic models increased sensitivity to pain. In acute model, we found that WIN 55,212-2 (almost high doses) decreases the level of pain mainly through CB1 receptor due to CB1 antagonist abrogates its protective effects, however, in formalin test CB2 receptors also had crucial roles in both phases at 3 mg/kg of WIN 55,212-2. In chronic model, WIN 55,212-2 (0.33, 1 and 3 mg/kg) significantly attenuated NTG-induced hyperalgesia through both CB1 and CB2 receptors. SIGNIFICANCE: Our data supported the argument that activation of CB1 and CB2 receptors by WIN 55,212-2 may be considered a new medication for migraine, however in lack of each receptor leads to different responses from deletion to the reduction of analgesic effects.

Vitamin D supplementation attenuates the behavioral scores of neuropathic pain in rats.

Objective(s): Neuropathic pain due to lesion or dysfunction of the peripheral or central nervous system is often refractory to the conventional analgesics. Currently, there is no proven treatment to prevent or cure neuropathic pain. A recent surge of new data suggests the potential effects of vitamin D in the medical community. This study was designed to determine whether acute or chronic vitamin D administration was effective in alleviating symptoms of neuropathic pain in a rat model of neuropathic pain. Materials and Methods: Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve in the rats that resulted in thermal hyperalgesia, mechanical, and cold allodynia. Results: Acute vitamin D injections (250, 500, and 1000 unit/kg i.p.) on the 7th, 14th, and 21st postoperative days could not attenuate mechanical and cold allodynia as well as heat hyperalgesia compared to CCI group. But when vitamin D (1000 unit/kg i.p.) administration was started on the first day after surgery and given daily until the 21st day, cold allodynia and heat hyperalgesia considerably were attenuated. However, no differences in paw withdrawal thresholds were observed. Conclusion: These results indicate that chronic vitamin D administrations can attenuate the behavioral scores of neuropathic pain in rats.

Anticonvulsant effects of thiamine on pentylenetetrazole-induced seizure in mice.

OBJECTIVES: Thiamine serves as a cofactor for several enzymes involved in brain function and neurotransmitters biosynthesis. Thiamine-dependent enzymes are important for oxidant stress defenses. Several studies have reported that thiamine deficiency in the central nervous system reduces seizure threshold. The present study was designed to investigate the effect of acute and chronic administration of thiamine alone and in combination with sub-effective dose of diazepam on pentylenetetrazole (PTZ)-induced tonic-clonic seizures in mice. METHODS: Animals were randomly divided into control and experimental groups. In experimental groups, thiamine (50, 100, and 200 mg/kg i.p.) was administered acutely or chronically (once a day, for 14 days). Slow intravenous infusion of PTZ (5 mg/ml) by infusion pump with a constant rate (0.3 ml/min) was used to induce clonic and tonic seizures. RESULTS: Acute injection of thiamine (50, 100, and 200 mg/kg i.p.) did not increase seizure threshold significantly, but chronic treatment with thiamine (200 mg/kg i.p.) increases the clonic and tonic seizure threshold. Moreover, the combination of sub-effective dose of thiamine (100 mg/kg) and diazepam (0.1 mg/kg) significantly increased seizure threshold and enhanced the anticonvulsant effect of diazepam at ineffective dose (0.1 mg/kg). DISCUSSION: Our results suggest that thiamine can be considered as a potential add-on treatment in deficient and non-deficient thiamine epileptic patients. Co-administration of this vitamin with classic antiepileptics to decrease the required doses of regular drugs may be recommended. Nevertheless, more well-designed studies may be executed to provide further accurate information.

Quetiapine reverses paclitaxel-induced neuropathic pain in mice: Role of alpha2- adrenergic receptors.

OBJECTIVES: Paclitaxel-induced peripheral neuropathy is a common adverse effect of cancer chemo -therapy. This neuropathy has a profound impact on quality of life and patient's survival. Preventing and treating paclitaxel-induced peripheral neuropathy is a major concern. First- and second-generation antipsychotics have shown analgesic effects both in humans and animals. Quetiapine is a novel atypical antipsychotic with low propensity to induce extrapyramidal or hyperprolactinemia side effects. The present study was designed to investigate the effects of quetiapine on the development and expression of neuropathic pain induced by paclitaxel in mice and the role of α2-adrenoceptors on its antinociception. MATERIALS AND METHODS: Paclitaxel (2 mg/kg IP) was injected for five consecutive days which resulted in thermal hyperalgesia and mechanical and cold allodynia. RESULTS: Early administration of quetiapine from the 1st day until the 5th day (5, 10, and 15 mg/kg PO) did not affect thermal, mechanical, and cold stimuli and could not prevent the development of neuropathic pain. In contrast, when quetiapine (10 and 15 mg/kg PO) administration was started on the 6th day after the first paclitaxel injections, once the model had been established, and given daily until the 10th day, heat hyperalgesia and mechanical and cold allodynia were significantly attenuated. Also, the effect of quetiapine on heat hyperalgesia was reversed by pretreatment with yohimbine, as an alpha-2 adrenergic receptor antagonist. CONCLUSION: These results indicate that quetiapine, when administered after nerve injury can reverse the expression of neuropathic pain. Also, we conclude that α2-adrenoceptors participate in the antinociceptive effects of quetiapine.

Assessment of Adverse Drug Reaction Due to Cancer Chemotherapy in a Teaching Oncology Hospital in Isfahan, Central of Iran.

INTRODUCTION: Adverse Drug Reactions (ADRs) are common in hospitalized oncology patients. The kinds of ADRs experienced by cancer patients are varied. Therefore, the identification of appropriate manner in order to prevent ADRs may improve patient outcome. AIMS: The present study evaluated the incidence, frequency and common types of adverse drug reactions among hospitalized oncology patients. METHODS: Patients hospitalized at a university oncology center (children and adult) during the calendar year 2012 were randomly selected. Data were collected by reviewing of medical records. The outcome measures included the incidence of observed ADRs and ADR-related admissions and achieving strategies to prevent the emergence of chemotherapy side effects. RESULTS: ADRs frequently occurred in the age group less than 20 years (22%). Prevalence of leukemia (27%), colon cancer (16.5%) and breast cancer (14%) was higher in our region. Most ADRs were recorded in patients receiving cisplatin (44%), doxorubicin (24%) and 5-fluouracil (20%) as chemotherapy. The most frequently observed ADRs were nauseavomiting, neutropenia and constipation in both pediatric and adult population. CONCLUSION: This study shows that ADRs occur more frequently in the pediatric group compared to adults. Therefore, optimum use of preventative strategy program may contribute to reducing the incidence and severity of ADRs especially in this group.

Antinociceptive effects of maprotiline in a rat model of peripheral neuropathic pain: possible involvement of opioid system.

OBJECTIVES: Neuropathic pain remains a clinical problem and is poorly relieved by conventional analgesics. This study was designed to determine whether maprotiline administration was effective in alleviating symptoms of neuropathic pain and whether the antinociceptive effect of maprotiline mediated through the opioid system. MATERIALS AND METHODS: Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve in rats, which resulted in thermal hyperalgesia, and mechanical and cold allodynia. Maprotiline (10, 20 and 40 mg/kg, IP) was administered on the 7(th) and 14(th) days after surgery. To study the role of the opioid system in the antinociceptive effects of maprotiline, maprotiline (20 mg/kg, IP) was administered in combination with naloxone (1 mg/kg, SC) on the 7(th) post-surgery day. Behavioral tests were done at 45 min after drug injections on the 7(th) and 14(th) days after surgery. RESULTS: Systemic administration of maprotiline blocked heat hyperalgesia, cold allodynia and reduced mechanical allodynia. Also antihyperalgesic effect of maprotiline was reversed by pretreatment with naloxone. CONCLUSION: Our results suggest that maprotiline can be considered a potential therapeutic for the treatment of neuropathic pain, and the opioid system may be involved in the antihyperalgesic effects of maprotiline.

The anti-inflammatory effects of venlafaxine in the rat model of carrageenan-induced paw edema.

OBJECTIVES: Recently anti-inflammatory effects of antidepressants have been demonstrated. Venlafaxine belongs to newer antidepressants with serotonin norepinephrine reuptake inhibition property. The pain alleviating properties of venlafaxine in different pain models such as neurogenic pain, diabetic neuropathy, and fibromyalgia have been demonstrated. Anti-inflammatory effects of venlafaxine and also its underlying mechanisms remain unclear. The present study was designed to evaluate the anti-inflammatory effects of venlafaxine and determine possible underlying mechanisms. MATERIALS AND METHODS: We examined the anti-inflammatory effects of intraperitoneal (IP) and intracerebroventricular (ICV) administration of venlafaxine in the rat model of carrageenan-induced paw edema. RESULTS: Our results showed that both IP (50 and 100 mg/kg) and ICV (50 and 100 µg/rat) injection of venlafaxine inhibited carrageenan-induced paw edema. Also IP and ICV administration of venlafaxine significantly decreased myeloperoxidase (MPO) activity and interleukin (IL)-1ß and tumor necrosis factor (TNF)-α production. Finally, we tried to reverse the anti-inflammatory effect of venlafaxine by yohimbine (5 mg/kg, IP), an alpha2-adrenergic antagonist. Our results showed that applied antagonist failed to change the anti-inflammatory effect of venlafaxine. CONCLUSION: These results demonstrated that venlafaxine has potent anti-inflammatory effect which is related to the peripheral and central effects of this drug. Also we have shown that anti-inflammatory effect of venlafaxine is mediated mostly through the inhibition of IL-1ß and TNF-α production and decreases MPO activity in the site of inflammation.

Venlafaxine Attenuates Heat Hyperalgesia Independent of Adenosine or Opioid System in a Rat Model of Peripheral Neuropathy.

Primarily opioidergic and adenosine mechanisms are considered to be involved in the antinociceptive effects of antidepressants. This study was designed to determine the efficacy of acute venlafaxine administration in alleviating symptoms of neuropathic pain and the role of endogenous adenosine and opioid systems in this effect of venlafaxine. We have evaluated the effect of caffeine, a non-selective adenosine A1 and A2 receptor antagonist and naloxone as an antagonist of opioid receptors on the antinociceptive effects of venlafaxine. Chronic constriction injury of the sciatic nerve resulted in thermal hyperalgesia, mechanical and cold allodynia in the rats. Animals were received on the 7(th) day after surgery, when the model had been fully established, venlafaxine (20 and 40 mg/Kg i.p.), or venlafaxine (40 mg/Kg) in combination with caffeine (5 mg/Kg i.p.) or naloxone (1 mg/Kg s.c.). Rats were tested for thermal reaction latencies, mechanical and cold allodynia 45 min after drug injection. Acute venlafaxine (40 mg/Kg i.p.) administration consistently decreased the thermal hyperalgesia and this effect was not blocked by concomitant caffeine or naloxone administration. There was no effect by either drug or the drug combination on the tactile and cold allodynia. The results of this study indicate that venlafaxine (40 mg/Kg i.p.) is effective in alleviating thermal hyperalgesia and this effect is independent through manipulation of adenosine or opioid system. This observation demonstrates that venlafaxine, which is a mixed inhibitor of norepinephrine and serotonin reuptake, differs from the other antidepressants in the mechanism of its antinociception action.

Neuroprotective, antimicrobial, antioxidant, chemotherapeutic, and antidiabetic properties of Salvia Reuterana: A mini review.

OBJECTIVES: Herbal medicine is known as a valid alternative treatment. Salvia Reuterana, which has been used in the Iranian traditional medicine, is mostly distributed in the central highlands of Iran. Salvia Reuterana is a medicinal herb with various therapeutic usages. The aim of the present review is to take account of pharmacological properties of Salvia Reuterana. MATERIALS AND METHODS: The present review summarizes the literature with respect to various pharmacological properties of Salvia Reuterana. RESULTS: Salvia Reuterana possesses neurological, antimicrobial, antioxidant, chemotherapeutic, and antidiabetic properties. CONCLUSIONS: Salvia Reuterana can be used as an alternative for treatment of several disorders.

The role of Bcl-2 family proteins in pulmonary fibrosis.

Pulmonary fibrosis is characterized by epithelial injury, abnormal tissue repair, fibroproliferation and loss of pulmonary function as a result of a complex interaction of multiple cellular and molecular processes. There is accumulating evidence in support of a role for apoptosis in the pathogenesis of interstitial lung diseases. The Bcl-2 (B-cell lymphoma-2) family of proteins, which consists of antiapoptotic and pro-apoptotic members, is a critical regulator for apoptosis and development of pulmonary fibrosis. The association between Bcl-2 family members and various pathways and mediators has been also described in the pulmonary fibrosis. This article reviews the recent advances regarding the roles of Bcl-2 family as the apoptosis-regulatory factors in pulmonary fibrosis from human tissue studies, animal models, ex vivo and in vitro studies. Further understanding of apoptosis signaling regulation through Bcl-2 family proteins in the lung tissue may lead to better design of new therapeutic interventions for pulmonary fibrosis.

Antinociceptive effects of venlafaxine in a rat model of peripheral neuropathy: role of alpha2-adrenergic receptors.

This study was designed to determine whether acute or chronic venlafaxine administration was effective in alleviating symptoms of neuropathic pain in a rat model of neuropathic pain, and whether the effect of venlafaxine involved manipulation of α2-adrenoceptors,by determining the effect of yohimbine, a α2-adrenoceptor antagonist on its actions. Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve in the rats that resulted in stimulus-evoked thermal hyperalgesia, tactile mechanical and cold allodynia. Acute venlafaxine injections (20 and 40 mg/kg i.p.) on the 7th, 14th and 21st postoperative days could not reduce tactile and cold hypersensitivity significantly compared to CCI group. But in these groups venlafaxine (40 mg/kg i.p.) blocked heat hyperalgesia. When venlafaxine (10 and 20mg/kg i.p.) administration was started on the first day after CCI and given daily until the 14th day, tactile hypersensitivity and heat hyperalgesia considerably were attenuated. But when venlafaxine (20mg/kg i.p.) treatment was initiated on the 10th day after CCI, once the model had been fully established, and given daily for 11 days, no differences in withdrawal thresholds were observed compared with CCI group however heat hyperalgesia significantly has been blocked. Also the effect of venlafaxine on heat hyperalgesia was reversed by pretreatment with yohimbine at all-time intervals. These results indicate that venlafaxine, when administered immediately after nerve injury, and for a sufficient period of time, can prevent the development and expression of neuropathic pain. Also we conclude that α2-adrenoceptors participate in the antinociceptive effects of venlafaxine.

Gabapentin enhances anti-nociceptive effects of morphine on heat, cold, and mechanical hyperalgesia in a rat model of neuropathic pain.

OBJECTIVES: Neuropathic pain is caused by lesions or diseases affecting the somatosensory system and often responds poorly to typical medications. In this study, we evaluated anti-nociceptive effects of morphine, gabapentin and their combination on heat hyperalgesia, cold and mechanical allodynia in chronic constriction injury (CCI) model of neuropathic pain in rats. MATERIALS AND METHODS: Morphine (2, 4 and 8 mg/kg) and gabapentin (5, 10 and 20 mg/kg) were administered either alone or in combination (morphine 2 mg/kg and gabapentin 5 mg/kg). RESULTS: Our results showed that morphine and gabapentin alone produce anti-nociceptive effects at higher doses (morphine 4 and 8 mg/kg and gabapentin 10 and 20 mg/kg) whereas their combination resulted in better analgesia at lower doses as compared to other treatment groups (morphine 2 mg/kg or gabapentin 5 mg/kg). CONCLUSION: These findings suggest that gabapentin potentiates the analgesic effects of morphine in the chronic constriction injury (CCI) model of neuropathic pain and combination of these drugs may be considered as a beneficial treatment for neuropathic pain.

Effect of diazepam on severity of acute pancreatitis: possible involvement of peripheral benzodiazepine receptors.

Acute pancreatitis is a lethal inflammatory condition of pancreas with high mortality rate. There is a pressing need for research to explore active agents and novel mechanisms involving in the treatment of pancreatitis. Clinical studies have shown after the initial acinar cell injury plasma levels of pro-inflammatory cytokines are elevated in patients with acute pancreatitis and the degree of cytokine elevation correlates with disease severity. Diazepam may decrease interleukin release from macrophages, suppress neutrophil activities, and exhibit anti-inflammatory effects. So it is expected that in vivo pretreatment of acute pancreatitis with different doses of diazepam can attenuate its severity. Thus, we evaluated the effects of diazepam, intraperitoneally (5, 10, and 20 mg/kg i.p.), intracerebroventricularly (ICV 10 µ g), and concurrently with flumazenil (1 mg/kg) on cerulein-induced acute pancreatitis in mice. Interestingly, the pretreatment with diazepam (5 mg/kg i.p.) reduced significantly the inflammatory response of acute pancreatitis by ameliorating pancreatic edema, amylase and lipase serum levels, myeloperoxidase activity, pancreatic TNF-alpha, and pathological alteration compared to control group. Diazepam i.c.v. was ineffective, suggesting that central benzodiazepine receptors have no significant role in this property. These results demonstrate that pretreatment with diazepam exhibits anti-inflammatory property in cerulein-induced acute pancreatitis possibly through peripheral benzodiazepine receptors.

Effect of Echium amoenum Fisch. et Mey a Traditional Iranian Herbal Remedy in an Experimental Model of Acute Pancreatitis.

Acute pancreatitis is a morbid inflammatory condition of pancreas with limited specific therapy. Enhanced oxidative stress plays an important role in induction and progression of acute pancreatitis. So reducing oxidative stress may relieve this pathogenic process. Echium amoenum Fisch. and Mey has been implemented in Iranian folk medicine for several centuries. Antioxidant, analgesic, immunomodulatory, and anxiolytic properties of E. amoenum suggest that this plant may have beneficial effects in the management of acute pancreatitis. The aim of this study was to evaluate the protective effect of petals of E. amoenum extract (EAE) on a murine model of pancreatitis. Acute pancreatitis was induced by five intraperitoneal (i.p.) injection of cerulein (50 µg/kg) with 1h intervals which was characterized by pancreatic inflammation and increase in the serum level of digestive enzymes, in comparison to normal mice. EAE (100, 200, and 400 mg/kg) was administered i.p., 30 minutes before induction of pancreatitis. Pretreatment with EAE (400 mg/kg) reduced significantly the inflammatory response of cerulein-induced acute pancreatitis by ameliorating pancreatic edema, amylase and lipase serum levels, proinflammatory cytokines, myeloperoxidase activity, lipid peroxidation and pathological alteration. These results show that EAE attenuates the severity of cerulein-induced acute pancreatitis with an anti-inflammatory, immunomodulatory and antioxidant effects.

Does Cisapride, as a 5HT(4) Receptor Agonist, Aggravate the Severity of TNBS-Induced Colitis in Rat?

There is a pressing need for research that will lead to the reveal of targets designed to analyse the possible pathways for the treatment of IBD. Because of the probable involvement of serotonin in inflammatory conditions of intestine and the important role of 5HT(4) receptors in GI function, the investigation of the role of 5HT(4) receptors in the pathogenesis of IBD will be interesting. The aim of this study was to investigate the effects of cisapride, a 5HT(4) receptor agonist, in trinitrobenzenesulfonic-acid-(TNBS) induced rat colitis. Two hours subsequent to induction of colitis using TNBS in rats, cisapride (2 mg/kg, intraperitoneally (i.p); 4 mg/kg, orally (p.o)) and dexamethasone (1 mg/kg, i.p; 2 mg/kg, p.o) were administrated for 6 days. Animals were thereafter euthanized; macroscopic, histological, and biochemical assessments and ELISA test were carried out on distal colon samples. Our data showed that dexamethasone treatment (i.p, p.o) significantly decreased macroscopic and microscopic damage and also biochemical markers, but there were no significant differences in aforementioned parameters between cisapride (i.p or p.o) and TNBS-treated rats. It can be deduced that because the severity of colitis produced by TNBS is massive (through various pathways), cisapride could not bring about more colitis damages through 5HT(4) receptors. Based on the present study further researches are required for investigating the exact roles of 5HT(4) receptors in the pathogenesis of ulcerative colitis.