Anti-inflammatory effect of acute stress on experimental colitis is mediated by cholecystokinin-B receptors

Gülpınar, Mehmet Ali; Özbeyli, Dilek; Arbak, Serap; Yeğen, Berrak Ç.

doi:10.1016/j.lfs.2003.12.009

Cited by 25 publications

(13 citation statements)

References 23 publications

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“…There is a long history of observations suggesting that psychological stress and anxiety contribute to the course of IBD [52,53], whereas chronic stress increases the severity of intestinal inflammation [54]. In parallel with previous studies demonstrating that psychological stress might amplify intestinal inflammation [55], the present data demonstrate that colitis increased the anxiety of the animals when placed on the hole-board.…”

Section: Discussionsupporting

confidence: 88%

Nicotine alleviates colitis-induced damage in rats via its anti-oxidative activity

Ozdemır

Tazegül

Kuru

et al. 2014

MMJ

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Inflammatory bowel disease (IBD) is an idiopathic chronic disease with probable genetic heterogeneity affecting nearly 30 million people worldwide [1]. Although it is welldocumented that smoking is associated with several diseases and with an increased morbidity and mortality of smokers [2], several epidemiological observations have demonstrated that the risk of developing ulcerative colitis (UC) is greater in both ex-smokers and non-smokers [3,4] than in smokers. Published evidence also suggests that as compared to a healthy population, a higher proportion of ABSTRACT Objective: Previous studies have demonstrated a higher incidence of ulcerative colitis in non-smokers. We investigated the beneficial effects of nicotine treatment on colitis-induced anxiety and oxidative colonic damage on rats.Materials and Methods: Wistar Albino (250-300 g) rats (n=40) were randomly divided into 5 groups as saline-treated colitis group, nicotine pre-treated colitis group, nicotine post-treated colitis group, continuously nicotine-treated colitis group and control group. Groups received intraperitoneal injections of saline or nicotine (0.1 mg/kg/day) for 15 days prior to and for 3 days following the colitis induction. Malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO), superoxide dismutase (SOD) and catalase (CAT) activities, histological evaluation and DNA fragmentation were studied in colonic samples. Anxiety levels were evaluated with the hole-board test. Results were evaluated using ANOVA and Mann-Whitney-U tests.Results: The saline-treated colitis group had increased MPO and MDA levels, DNA fragmentation and histological damage scores when compared with the control group. In the nicotinetreated groups MPO and MDA levels and DNA fragmentation were reduced, with lower histologic damage scores. Reduced SOD, CAT and GSH levels were also increased in nicotine-treated groups.Conclusion: This study demonstrates antioxidant effects of nicotine treatment in the acetic acid-induced colitis model including an increased antioxidant capacity, reduced migration of neutrophils to the inflamed colon and a reduction of membrane damage.Key words: Ulcerative colitis, Anxiety, Myeloperoxidase, Superoxide dismutase, Glutathione, Catalase ÖZET Amaç: Epidemiyolojik çalışmalar ülseratif kolitin sigara kullanmayanlarda daha sık görüldüğünü bildirmektedir. Bu çalışmada kolitle oluşan oksidan hasar ve anksiyete üzerine nikotin ön tedavisinin ve/veya kolit sonrası tedavinin olası yararlı etkilerinin araştırılması amaçlanmıştır.Gereç ve Yöntem: Wistar Albino (250-300 g) sıçanlar (n=40), serum fizyolojik (SF) verilen, ön-tedavili, tedavili ve ön-tedavi+ tedavili kolit grubu ve kontrol grubu olmak üzere beşe ayrıldı. Kolit öncesi 15 gün ve kolit sonrasında 3 gün sıçanlara intraperitoneal SF ya da nikotin (0,1 mg/kg/gün) uygulandı. Kolon örneklerinde oksidan hasarı belirlemek için malondialdehid (MDA), miyeloperoksidaz (MPO) aktivitesi, glutatyon (GSH), süperoksit dismutaz (SOD), katalaz ve DNA fragmantasyonu ölçümleri ile histolojik...

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Section: Discussionsupporting

confidence: 88%

Nicotine alleviates colitis-induced damage in rats via its anti-oxidative activity

Ozdemır

Tazegül

Kuru

et al. 2014

MMJ

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“…Stimulation of cholecystokinin (CCK) signaling by sincalide has been shown to reduce acute colitis in rats . Interestingly, our screen also detected a proinflammatory effect of the CCK receptor antagonist lorglumide that is consistent with observations of exacerbated acute colitis in rats treated with CCK receptor antagonists . As sincalide, as with cabergoline, has well defined molecular targets, we chose to further define the role of the CCK signaling pathway in our zebrafish acute enterocolitis models.…”

Section: Resultssupporting

confidence: 59%

A whole animal chemical screen approach to identify modifiers of intestinal neutrophilic inflammation

et al. 2017

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By performing two high-content small molecule screens on DSS- and TNBS-induced zebrafish enterocolitis models of inflammatory bowel disease, we have identified novel anti-inflammatory drugs from the John Hopkins Clinical Compound Library that suppress neutrophilic inflammation. Live imaging of neutrophil distribution was used to assess the level of acute inflammation and concurrently screen for off-target drug effects. Supporting the validity of our screening strategy, most of the anti-inflammatory drug hits were known antibiotics or anti-inflammatory agents. Novel hits included cholecystokinin (CCK) and dopamine receptor agonists. Using a pharmacological approach, we show that while CCK and dopamine receptor agonists alleviate enterocolitis-associated inflammation, receptor antagonists exacerbate inflammation in zebrafish. This work highlights the utility of small molecule screening in zebrafish enterocolitis models as a tool to identify novel bioactive molecules capable of modulating acute inflammation.

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“…This may contribute to the increased epithelial damage score and the increased cytokine secretion found after prolonged CSC exposure. Indeed, a blunted activation of the HPA axis during stressor exposure makes the animals more vulnerable for chemically induced inflammations (32)(33)(34)(35). Moreover, the diminished GC sensitivity found in LPS-stimulated immune cells of CSC mice may additionally contribute to the increased colonic inflammation found on d 14 and 20 of CSC.…”

Section: Effects Of Csc Exposure On Colonic Inflammationmentioning

confidence: 99%

Adrenal Insufficiency and Colonic Inflammation after a Novel Chronic Psycho-Social Stress Paradigm in Mice: Implications and Mechanisms

et al. 2007

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We investigated chronic psycho-social stress effects on stress-related parameters and on pathohistological changes in the murine colon. Moreover, we aimed to reveal the involvement of adrenal glucocorticoids in chronic stress effects. Chronic subordinate colony housing (CSC, 19 d) resulted in reduced body weight gain, thymus atrophy, adrenal hypertrophy, increased plasma norepinephrine, and increased anxiety. With respect to the time course of CSC effects, CRH mRNA in the hypothalamic paraventricular nucleus, light phase corticosterone and tyrosine hydroxylase expression in colonic tissue were found to be increased, whereas tyrosine hydroxylase expression in the locus coeruleus was found to be decreased on d 2 of CSC; these parameters returned to control levels thereafter. Nevertheless, after 19 d of CSC exposure, the adrenal corticosterone responses in vivo and in vitro, and glucocorticoid sensitivity of isolated splenic cells were found to be decreased. Importantly, in CSC mice a significant histological damage of the colon was found beginning on d 14 of CSC exposure. Additionally, pro- and antiinflammatory cytokine secretion by mesenteric lymph node cells was increased after CSC exposure. Adrenalectomy before CSC at least partially prevented these chronic stress effects as reflected by less increase in proinflammatory cytokine secretion and an equal histological damage score in adrenalectomized compared with sham-operated CSC mice. In conclusion, chronic exposure to CSC alters relevant neuronal, neuroendocrine and immune functions that could be directly or indirectly involved in the damage of the histological integrity of the colon comparable with that seen during the development of colitis.

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Anti-inflammatory effect of acute stress on experimental colitis is mediated by cholecystokinin-B receptors

Cited by 25 publications

References 23 publications

Nicotine alleviates colitis-induced damage in rats via its anti-oxidative activity

Nicotine alleviates colitis-induced damage in rats via its anti-oxidative activity

A whole animal chemical screen approach to identify modifiers of intestinal neutrophilic inflammation

Adrenal Insufficiency and Colonic Inflammation after a Novel Chronic Psycho-Social Stress Paradigm in Mice: Implications and Mechanisms

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