Dexmedetomidine ameliorates TNBS-induced colitis by inducing immunomodulator effect

Kayhan, Gülay Erdoğan; Gül, Mehmet; Kayhan, Basak; Gedik, Ender; Özgül, Ülkü; Kurtoğlu, Elçin Latıfe; Durmuş, Mahmut; Ersoy, M. Özcan

doi:10.1016/j.jss.2013.03.028

Cited by 17 publications

(15 citation statements)

References 39 publications

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“…These findings were later corroborated by another clinical study (Furlan et al, 2006), and more recently also by animal experiments (Erdogan Kayhan et al, 2013). In contrast, there is evidence that activation of a 2 -ARs localized on macrophages and neutrophils induces the release of proinflammatory cytokines (Spengler et al, 1994;Flierl et al, 2007) and enhances acute inflammatory lung injury in rats and mice (Flierl et al, 2007).…”

Section: Discussionmentioning

confidence: 53%

“…These models differ in several aspects, such as pathomechanism, clinical/-histologic picture, and cytokine profile (Strober et al, 2002;Alex et al, 2009); therefore, it is possible that a drug is able to influence the development of inflammation in one, but not in another model (Park et al, 2004). Nevertheless, it has to be emphasized that, regarding the role of a 2 -ARs, controversial results were reported by using the same colitis model (TNBS) as well (Bai et al, 2009;Erdogan Kayhan et al, 2013). Thus, other factors, such as using different a 2 -AR ligands with potential additional receptorial actions (dexmedetomidine, UK14304), different amounts of the chemical inducer (2.5 and 3.75 mg TNBS), or different ages of experimental animals (5-6 and 7-8 weeks), may also contribute to the diverging findings.…”

Section: Discussionmentioning

confidence: 99%

“…It was demonstrated that pharmacological blockade of a 2 -ARs suppressed the production of proinflammatory cytokines by lamina propria mononuclear cells and ameliorated acute murine colitis (Bai et al, 2009;Bai et al, 2015). In contrast, activation of a 2 -ARs by dexmedetomidine reduced the symptoms of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-evoked colitis by inducing a versatile immunomodulatory effect (Erdogan Kayhan et al, 2013), and chronic administration of clonidine (CLO), another a 2 -AR agonist, induced clinical, endoscopic, as well as histologic improvement in patients with UC (Lechin et al, 1985;Furlan et al, 2006). Thus, it is still a matter of debate whether the activation of a 2 -ARs confers deleterious or protective effects on intestinal inflammation.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of 2A-Adrenoceptors Ameliorates Dextran Sulfate Sodium-Induced Acute Intestinal Inflammation in Mice

Zádori

Tóth

Fehér

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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It has been hypothesized that a 2 -adrenoceptors (a 2 -ARs) may be involved in the pathomechanism of colitis; however, the results are conflicting because both aggravation and amelioration of colonic inflammation have been described in response to a 2 -AR agonists.Therefore, we aimed to analyze the role of a 2 -ARs in acute murine colitis. The experiments were carried out in wild-type, a 2A -, a 2B -, and a 2C -AR knockout (KO) C57BL/6 mice. Colitis was induced by dextran sulfate sodium (DSS, 2%); alpha 2 -AR ligands were injected i.p. The severity of colitis was determined both macroscopically and histologically. Colonic myeloperoxidase (MPO) and cytokine levels were measured by enzyme-linked immunosorbent assay and proteome profiler array, respectively. The nonselective a 2 -AR agonist clonidine induced a modest aggravation of DSSinduced colitis. It accelerated the disease development and markedly enhanced the weight loss of animals, but did not influence the colon shortening, tissue MPO levels, or histologic score. Clonidine induced similar changes in a 2B -and a 2C -AR KO mice, whereas it failed to affect the disease activity index scores and caused only minor weight loss in a 2A -AR KO animals. In contrast, selective inhibition of a 2A -ARs by BRL 44408 significantly delayed the development of colitis; reduced the colonic levels of MPO and chemokine (C-C motif) ligand 3, chemokine (C-X-C motif) ligand 2 (CXCL2), CXCL13, and granulocytecolony stimulating factor; and elevated that of tissue inhibitor of metalloproteinases-1. In this work, we report that activation of a 2 -ARs aggravates murine colitis, an effect mediated by the a 2A -AR subtype, and selective inhibition of these receptors reduces the severity of gut inflammation.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of 2A-Adrenoceptors Ameliorates Dextran Sulfate Sodium-Induced Acute Intestinal Inflammation in Mice

Zádori

Tóth

Fehér

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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“…Sedatives influence a number of physiological systems and responses, including the immune system, leading to the concept of sedative-induced immunomodulation (Galley et al, 2000; Taniguchi et al, 2004; Maclaren, 2009; Qiao et al, 2009; Sanders et al, 2009; Kayhan et al, 2013). Because of the potential for infections and sepsis in intensive care settings, it has been suggested that immunomodulatory properties should be considered in the clinical decision-making process regarding the inclusion of sedatives in drug regimens (Sanders et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine and regulation of splenic sympathetic nerve discharge

Kenney¹,

Larsen²,

McMurphy³

et al. 2014

Autonomic Neuroscience

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Recent lines of inquiry indicate sedatives can influence the immune system, leading to the concept of sedative-induced immunomodulation. It has been hypothesized that sedatives may alter immune responses by modulating the sympathetic nervous system, however, little information is known regarding the effects of sedatives on regulation of splenic sympathetic nerve discharge (SND), a significant omission based on the functional role that changes in splenic SND exert on splenic cytokine gene expression. The present investigation determined the effect of systemic Dexmedetomidine (Dex) administration on the level of directly-recorded splenic SND and tested the hypothesis that the intravenous administration of Dex would inhibit splenic SND in anesthetized rats. The present results demonstrate for the first time that intravenous Dex administration significantly reduces splenic sympathetic nerve outflow in baroreceptor-intact and sinoaortic-denervated rats, indicating that Dex administration alters the central regulation of splenic SND. The present results provide new information regarding the effect of a centrally-acting alpha2-adrenergic agonist on the level of sympathetic nerve outflow to a secondary lymphoid organ that plays a critical role in peripheral immune responses.

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“…These findings corroborate the results of studies previously reported by other authors. 10,11 In our investigation, the efficacy and safety of incision local ropivacaine analgesia for patients undergoing hepa- tectomy was evaluated by comparing the postoperative analgesic effect and adverse reactions following open hepatectomy. Ropivacaine is a long-acting local amide anesthetic with low neurotoxicity and cardiotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Postoperative local incision analgesia for acute pain treatment in patients with hepatocellular carcinoma

et al. 2018

Rev. Assoc. Med. Bras.

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Objective: The present study aimed to investigate the analgesic effect and safety of using local incision analgesia to treat acute postoperative pain in patients with hepatocellular carcinoma (HCC). Method: A cohort of 60 patients undergoing liver cancer resection was randomly divided into three groups (n=20 per group): local incision analgesia (LIA) group, which received local infiltration with ropivacaine combined with a postoperative analgesia pump; intravenous patient-controlled analgesia (PCA) group, which received fentanyl intravenous analgesia postoperatively; and the control group, which received tramadol hydrochloride injection postoperatively according to the NRS scoring system. The postoperative analgesic effect in each group was compared and tumor recurrence (survival) was analyzed using the Kaplan-Meier method. Results: NRS scores, rate of analgesic usage, ambulation time (h) and intestinal function recovery time (h) were significantly reduced in LIA group compared with the control group at each postoperative time point (6, 12, 24 and 48 hours; p<0.05). Additionally, the NRS scores of LIA patients at 12 hours post-surgery was significantly reduced compared with PCA group (p<0.05), and the occurrence of postoperative adverse events in LIA group was significantly lower than that in PCA group (p<0.05). Survival analysis demonstrated that the mean survival time (tumor recurrence) was significantly increased in LIA group compared with the control group (χ 2 =4.749; p=0.029). Conclusion: Local incision analgesia improves the analgesic effect, causes fewer adverse reactions and increases postoperative survival time. Our study demonstrated that local incision analgesia is a safe and effective method of postoperative pain management following hepatectomy.

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Dexmedetomidine ameliorates TNBS-induced colitis by inducing immunomodulator effect

Cited by 17 publications

References 39 publications

Inhibition of 2A-Adrenoceptors Ameliorates Dextran Sulfate Sodium-Induced Acute Intestinal Inflammation in Mice

Inhibition of 2A-Adrenoceptors Ameliorates Dextran Sulfate Sodium-Induced Acute Intestinal Inflammation in Mice

Dexmedetomidine and regulation of splenic sympathetic nerve discharge

Postoperative local incision analgesia for acute pain treatment in patients with hepatocellular carcinoma

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