Susceptibility of Lewis and Fischer rats to stress-induced worsening of TNB-colitis: protective role of brain CRF

1999 ◽  
Vol 276 (4) ◽  
pp. G1027-G1036 ◽  
Author(s):  
Mulugeta Million ◽  
Yvette Taché ◽  
Peter Anton
Keyword(s):  
Experimental Colitis ◽  
Plasma Corticosterone ◽  
Protective Role ◽  
Histological Evaluation ◽  
Trinitrobenzenesulfonic Acid ◽  
Response To Stress ◽  
Intracerebroventricular Injections ◽  
Fischer Rats ◽  
Inbred Rat

We assessed the role of central corticotropin-releasing factor (CRF) in stress-induced worsening of colitis in inbred rat strains with hypo (Lewis/N) and hyper (Fischer344/N) CRF responses to stress. Intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid (TNB) induced colitis of similar severity in both strains as assessed on day 7 by macroscopic scoring, histological evaluation, tissue myeloperoxidase (MPO) activity, and decrease in food intake and body weight. Colitis was inhibited by daily intracerebroventricular injections of CRF in both strains. Chronic stress (3 h/day, water avoidance or wrap restraint on alternate days for 6 days) aggravated colitis more in Lewis than Fischer rats (71 and 22% further increase in MPO activity, respectively). The CRF antagonist astressin injected intracerebroventricularly enhanced the colitis response to stress and caused mortality in both strains. Fischer rats had higher plasma corticosterone levels 20 min after stress alone on day 1 and after TNB plus stress on days 1 and 3 compared with Lewis. These data show that central CRF restrains the proinflammatory action of stress in experimental colitis.

scholarly journals Protective role of syndecan-4 in experimental colitis

2012 ◽  
Vol 71 (Suppl 1) ◽  
pp. A76.1-A76
Author(s):  
A Stratis ◽  
D Bettenworth ◽  
K Neugebauer ◽  
M Fröhling ◽  
P Paruzel ◽  
...  
Keyword(s):  
Experimental Colitis ◽  
Protective Role

Central interleukin-1 receptors contribute to suppression of feeding after acute colitis in the rat

1994 ◽  
Vol 266 (5) ◽  
pp. R1659-R1663 ◽  
Author(s):  
K. J. McHugh ◽  
S. M. Collins ◽  
H. P. Weingarten
Keyword(s):  
Receptor Antagonist ◽  
Interleukin 1 ◽  
Chronic Administration ◽  
Experimental Colitis ◽  
Trinitrobenzenesulfonic Acid ◽  
Acute Colitis ◽  
Osmotic Minipump ◽  
Intrarectal Administration

Experimental colitis, induced in rats by intrarectal administration of trinitrobenzenesulfonic acid (TNB), results in a suppression of eating for 3 days. Because interleukin-1 (IL-1) is elevated within 24 h after TNB treatment, and because chronic administration of IL-1 leads to a pattern of anorexia similar to that seen after TNB, we evaluated the role of endogenous IL-1 in the anorexia observed in the TNB model. Human recombinant IL-1 receptor antagonist (rhIL-1ra) was administered chronically via osmotic minipump either peripherally or centrally after TNB treatment. Peripheral delivery of 40 micrograms/h rhIL-1ra significantly attenuated TNB-induced anorexia. However, 24 micrograms/h rhIL-1ra attenuated TNB-induced anorexia only when delivered centrally, not peripherally. These findings implicate central IL-1 receptors in the suppression of eating during acute experimental colitis but leave open a possible involvement of peripheral IL-1 receptors.

Protective role of M-CSF dependent macrophages in experimental colitis in mice

2000 ◽  
Vol 32 ◽  
pp. A89
Author(s):  
F. Galeazzi ◽  
C.M. Hogaboam ◽  
B.A. Vallance ◽  
G.C. Sturniolo ◽  
S.M. Collins
Keyword(s):  
Experimental Colitis ◽  
Protective Role

HPA-axis responses during experimental colitis in the rat

2002 ◽  
Vol 282 (5) ◽  
pp. R1348-R1355 ◽  
Author(s):  
Kensaku Kojima ◽  
Yoshihisa Naruse ◽  
Norio Iijima ◽  
Naoki Wakabayashi ◽  
Shoji Mitsufuji ◽  
...  
Keyword(s):  
Food Intake ◽  
Hpa Axis ◽  
Mrna Level ◽  
Experimental Colitis ◽  
Plasma Corticosterone ◽  
Acth Level ◽  
Trinitrobenzenesulfonic Acid ◽  
Plasma Acth ◽  
Healthy Control ◽  
Inflammatory Bowel

We investigated the responses of the hypothalamic-pituitary-adrenal (HPA) axis during experimental colitis induced by intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid in the rat. On days 3 and 7 after induction of colitis, the corticotropin-releasing hormone (CRH) mRNA level in the parvocellular paraventricular nucleus (pPVN) of the hypothalamus was reduced, the plasma ACTH level remained at the basal level, and the plasma corticosterone (Cort) level was high. Induction of colitis on day 3 after adrenalectomy with Cort pellet replacement (ADX + Cort) resulted in a marked increase in CRH mRNA on day 7 after induction of colitis compared with noncolitic ADX + Cort animals. Pair feeding to match the food intake of the colitic animals resulted in no significant change in CRH mRNA in the pPVN, plasma ACTH, and Cort compared with healthy control animals. These findings indicated that CRH mRNA expression in the pPVN was inhibited by glucocorticoid feedback during this experimental colitis, and the decrease in food intake during colitis was not simply responsible for the expression of CRH mRNA. It is inferred that the HPA axis including the CRH level in the pPVN is altered in patients with inflammatory bowel disease.

Ischemia in normoglycemic and hyperglycemic rats: plasma energy substrates and hormones

1990 ◽  
Vol 258 (5) ◽  
pp. E767-E774
Author(s):  
J. Lundgren ◽  
A. Mans ◽  
B. K. Siesjo
Keyword(s):  
Ketone Bodies ◽  
Plasma Concentrations ◽  
Plasma Corticosterone ◽  
Rat Plasma ◽  
Protective Role ◽  
Forebrain Ischemia ◽  
Energy Substrates ◽  
Plasma Energy ◽  
Membrane Changes

Seizures are a documented complication to cerebral ischemia. After 10 min of forebrain ischemia in rats, preischemic hyperglycemia invariably leads to severe, most often fatal epileptic attacks. This outcome is related to the exaggerated lactic acidosis, which has been suggested as a possible contributor to severe membrane changes and widespread edema. To find out if circulating hormones or plasma energy substrates modulate this additive damage caused by the hyperglycemia, plasma concentrations of of corticosterone, epinephrine, norepinephrine, dopamine, glucagon, insulin, glucose, free fatty acids (FFA), 3-hydroxybutyrate, and acetoacetate were measured before and in the early recirculation period after 15 min of forebrain ischemia in the rat. Plasma corticosterone levels did not differ between the normo- and hyperglycemic groups. Although not significantly different from control, the catecholamine levels showed a tendency to be higher in the hyperglycemic groups. Therefore, because catecholamines have been reported to have a protective effect during ischemia the present result cannot explain why hyperglycemia aggravates the ischemic damage. Insulin levels seemed to increase during ischemia but not significantly. Levels quickly returned to normal after 30 min of recirculation. FFA concentrations were reduced after the induction of ischemia and appeared lower in all hyperglycemic groups. The level of one of the ketone bodies, 3-hydroxybutyrate, showed a significant decrease in hyperglycemic ischemia in all groups compared with normoglycemic ischemia. The same tendency was seen for acetoacetate. Results are compatible with a protective role of ketone bodies in ischemia. It is concluded that among the hormones and substrates studied only the ketone body concentrations qualify as a modulator of the exaggerated brain damage after ischemia in hyperglycemic subjects.

Abstract 150: S-nitrosylation Of Thioredoxin1 At Cysteine 73 Promotes Trans-nitrosylation, Autophagy And Cell Survival During Glucose Deprivation.

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Narayani Nagarajan ◽  
Sebastiano Sciarretta ◽  
Junichi Sadoshima
Keyword(s):  
Cell Survival ◽  
Protein S ◽  
Glucose Deprivation ◽  
Protective Role ◽  
Redox Activity ◽  
Oxidoreductase Activity ◽  
Response To Stress ◽  
Thioredoxin 1 ◽  
Biotin Switch

Thioredoxin-1 (Trx1) is a key antioxidant protein that is known to play a protective role in the heart during oxidative stress mainly through its oxidoreductase activity. Trx1 can be S-nitrosylated and, in turn, can trans-nitrosylate other proteins. However, the role of Trx1-dependent S-nitrosylation in cardiomyocytes (CMs) is not known. Here, we investigated the role of Trx1-mediated protein S-nitrosylation in the regulation of CM survival in response to stress. Using the biotin-switch assay, we found that wild-type Trx1 (Trx1WT) was S-nitrosylated, whereas the extent of S-nitrosylation was attenuated in Trx1C73S, suggesting that Trx1 is S-nitrosylated at Cys73. Also, we observed that the redox activity of Trx1 was intact in the Trx1C73S mutant. Overall protein S-nitrosylation in rat neonatal CMs was increased in response to 4 hrs of glucose deprivation (GD). Using biotin-switch assay and immunocytochemistry (fluorescent staining of s-nitrosylated cysteines), we observed that overexpression of Trx1WT increased, whereas short-hairpin RNA-mediated knockdown of Trx1 (shTrx1) or overexpression of Trx1C73S decreased, total protein S-nitrosylation in response to GD. These results suggest that Trx1Cys73 plays a key role in the regulation of protein S-nitrosylation in CMs during GD. Overexpression of Trx1 increased CM survival after 24 hrs of GD (Trx1WT vs. LacZ: propidium iodide assay, 0.5 ± 0.08-fold, p<0.01). Conversely, shTrx1 or overexpression of Trx1C73S increased cell death during GD (Trx1C73S vs. LacZ: 1.7 ± 0.034-fold, p<0.05). Autophagy is a pro-survival mechanism during GD. Therefore, we tested the effect of Trx1 on autophagy. After 4 hrs of GD, knockdown of Trx1 or overexpression of Trx1C73S decreased autophagy compared to control cells (LC3-II/LC3-I, 0.7-fold; autophagosomes, 0.83 ± 0.16-fold; autolysosomes, 0.62 ± 0.13-fold, p<0.005). Taken altogether, our results suggest that Trx1 promotes autophagy during GD through a trans-nitrosylation dependent mechanism. S-nitrosylation of Trx1 at Cys73 is associated with an overall increase in protein S-nitrosylation in CMs and promotes autophagy and thus, cell survival during GD.

Incrimination of anaerobic bacteria in the induction of experimental colitis

1997 ◽  
Vol 272 (1) ◽  
pp. G10-G15 ◽  
Author(s):  
A. Garcia-Lafuente ◽  
M. Antolin ◽  
F. Guarner ◽  
E. Crespo ◽  
A. Salas ◽  
...  
Keyword(s):  
Anaerobic Bacteria ◽  
Experimental Colitis ◽  
Mucosal Damage ◽  
Trinitrobenzenesulfonic Acid ◽  
Sterile Culture ◽  
Colonic Flora ◽  
Submucosal Lesions ◽  
Eicosanoid Release ◽  
Transmural Inflammation

Commensal bacteria may participate in the pathogenesis of bowel inflammation. We studied the role of bacteria from the rat colonic flora on transmural inflammation induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). First, bacterial translocation to the colonic wall after induction of colitis was assessed by microbiological and histological methods. Second, rats with a colonic segment excluded from fecal transit were prepared for recolonization with preselected bacteria and used to test the effects of different species on inflammation (eicosanoid release, tissue myeloperoxidase) and damage (histology). Six strains (three aerobes and three anaerobes) were identified in colonic tissue 24 h after induction of colitis. Acridine staining showed bacteria in necrotic areas of the mucosa and invading the submucosa. Rats with excluded colon and sterile culture of luminal washings showed mild inflammation and low mucosal damage in response to TNBS. Rats colonized with anaerobes showed significantly higher eicosanoid release than rats colonized with aerobes only. Moreover, submucosal-lesions were mostly observed in rats with anaerobes. Our findings suggest that colonic anaerobes play a key role in transmural inflammation.

Beneficial effects of local or systemic lidocaine in experimental colitis

1994 ◽  
Vol 266 (4) ◽  
pp. G560-G567 ◽  
Author(s):  
D. M. McCafferty ◽  
K. A. Sharkey ◽  
J. L. Wallace
Keyword(s):  
Experimental Colitis ◽  
Enteric Neurons ◽  
Histological Evaluation ◽  
Mucosal Mast Cell ◽  
Myeloperoxidase Activity ◽  
Trinitrobenzenesulfonic Acid ◽  
Cell Hyperplasia ◽  
Beneficial Effects ◽  
Granulocyte Infiltration ◽  
Substance P Receptor

Neuropeptides liberated from enteric neurons have been suggested to contribute to the inflammatory process in colitis. Based in part on this evidence, lidocaine enemas have recently been suggested as a treatment for ulcerative colitis, but their effects have yet to be fully characterized. We have assessed the effects of lidocaine on the development and maintenance of colitis induced by trinitrobenzenesulfonic acid (TNBS) in rats. In the initial experiments, rats were given lidocaine [5-100 mg/kg intrarectally] 30 min before TNBS administration, and the severity of colitis was assessed 6-24 h later. In subsequent experiments, rats received lidocaine intrarectally or subcutaneously 30 min before TNBS administration and once daily for 7 days. The severity of colitis was assessed by blind macroscopic scoring, measurement of myeloperoxidase activity, and histological evaluation. Lidocaine dose dependently reduced the severity of colitis and the infiltration of granulocytes at 24 h and 7 days post-TNBS. At the latter time point, lidocaine was also found to improve the histological appearance of the tissue and significantly reduce mucosal mast cell hyperplasia. Beneficial effects were also evident when intrarectal lidocaine treatment was initiated after induction of colitis or when lidocaine was given subcutaneously. Granulocyte infiltration into the colon could also be attenuated by a substance P receptor antagonist. These results suggest that lidocaine can exert anti-inflammatory effects in colitis, perhaps by virtue of its effects on intrinsic and/or extrinsic nerves.

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