scholarly journals Sigma-1 Receptor Engages an Anti-Inflammatory and Antioxidant Feedback Loop Mediated by Peroxiredoxin in Experimental Colitis

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1081
Author(s):  
Nikoletta Almási ◽  
Szilvia Török ◽  
Zsuzsanna Valkusz ◽  
Máté Tajti ◽  
Ákos Csonka ◽  
...  
Keyword(s):  
Experimental Colitis ◽  
The Body ◽  
Male Rats ◽  
Trinitrobenzenesulfonic Acid ◽  
Simultaneous Treatment ◽  
Sigma 1 Receptor ◽  
Beneficial Effects ◽  
Chronic Inflammatory Condition ◽  
Sigma 1 ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD), comprising Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory condition of the gastrointestinal tract. Since the treatment of IBD is still an unresolved issue, we designed our study to investigate the effect of a novel therapeutic target, sigma-1 receptor (σ1R), considering its ability to activate antioxidant molecules. As a model, 2,4,6-trinitrobenzenesulfonic acid (TNBS) was used to induce colitis in Wistar–Harlan male rats. To test the beneficial effects of σ1R, animals were treated intracolonically (i.c.): (1) separately with an agonist (fluvoxamine (FLV)), (2) with an antagonist of the receptor (BD1063), or (3) as a co-treatment. Our results showed that FLV significantly decreased the severity of inflammation and increased the body weight of the animals. On the contrary, simultaneous treatment of FLV with BD1063 diminished the beneficial effects of FLV. Furthermore, FLV significantly enhanced the levels of glutathione (GSH) and peroxiredoxin 1 (PRDX1) and caused a significant reduction in 3-nitrotyrosine (3-NT) levels, the effects of which were abolished by co-treatment with BD1063. Taken together, our results suggest that the activation of σ1R in TNBS-induced colitis through FLV may be a promising therapeutic strategy, and its protective effect seems to involve the antioxidant pathway system.

scholarly journals Lessons on the Sigma-1 Receptor in TNBS-Induced Rat Colitis: Modulation of the UCHL-1, IL-6 Pathway

2020 ◽  
Vol 21 (11) ◽  
pp. 4046 ◽  
Author(s):  
Nikoletta Almási ◽  
Szilvia Török ◽  
Szabolcs Dvorácskó ◽  
Csaba Tömböly ◽  
Ákos Csonka ◽  
...  
Keyword(s):  
Radioligand Binding ◽  
Binding Capacity ◽  
Treatment Options ◽  
Experimental Colitis ◽  
Binding Studies ◽  
Trinitrobenzenesulfonic Acid ◽  
Sigma 1 Receptor ◽  
Sigma 1 ◽  
Anti Inflammatory ◽  
Endothelial Nitric Oxide

Inflammatory Bowel Disease (IBD) is an autoimmune ailment of the gastrointestinal (GI) tract, which is characterized by enhanced activation of proinflammatory cytokines. It is suggested that the sigma-1 receptor (σ1R) confers anti-inflammatory effects. As the exact pathogenesis of IBD is still unknown and treatment options are limited, we aimed to investigate the effects of σ1R in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced experimental colitis. To this end, male Wistar–Harlan rats were used to model colitic inflammation through the administration of TNBS. To investigate the effects of σ1R, Fluvoxamine (FLV, σ1R agonist) and BD1063 (σ1R antagonist) were applied via intracolonic administration to the animals once a day for three days. Our radioligand binding studies indicated the existence of σ1Rs as [3H](+)-pentazocine binding sites, and FLV treatment increased the reduced σ1R maximum binding capacity in TNBS-induced colitis. Furthermore, FLV significantly attenuated the colonic damage, the effect of which was abolished by the administration of BD1063. Additionally, FLV potentially increased the expression of ubiquitin C-terminal hydrolase ligase-1 (UCHL-1) and the levels of endothelial nitric oxide synthase (eNOS), and decreased the levels of interleukin-6 (IL-6) and inducible NOS (iNOS) expression. In summary, our study offers evidence for the anti-inflammatory potential of FLV and σ1R in experimental colitis, and our results present a promising approach to the development of new σ1R-targeted treatment options against IBD.

scholarly journals A comparative study of the preventative effects exerted by two probiotics,Lactobacillus reuteriandLactobacillus fermentum, in the trinitrobenzenesulfonic acid model of rat colitis

2007 ◽  
Vol 97 (1) ◽  
pp. 96-103 ◽  
Author(s):  
Laura Peran ◽  
Saleta Sierra ◽  
Mònica Comalada ◽  
Federico Lara-Villoslada ◽  
Elvira Bailón ◽  
...  
Keyword(s):  
Lactobacillus Reuteri ◽  
Experimental Colitis ◽  
No Synthase ◽  
Glutathione Depletion ◽  
Myeloperoxidase Activity ◽  
Trinitrobenzenesulfonic Acid ◽  
Beneficial Effects ◽  
Colony Forming Units ◽  
Inflammatory Bowel ◽  
Anti Inflammatory

The intestinal anti-inflammatory effects of two probiotics isolated from breast milk,Lactobacillus reuteriandL. fermentum, were evaluated and compared in the trinitrobenzenesulfonic acid (TNBS) model of rat colitis. Colitis was induced in rats by intracolonic administration of 10 mg TNBS dissolved in 50 % ethanol (0·25 ml). EitherL. reuteriorL. fermentumwas daily administered orally (5 × 108colony-forming units suspended in 0·5 ml skimmed milk) to each group of rats (n10) for 3 weeks, starting 2 weeks before colitis induction. Colonic damage was evaluated histologically and biochemically, and the colonic luminal contents were used for bacterial studies and for SCFA production. Both probiotics showed intestinal anti-inflammatory effects in this model of experimental colitis, as evidenced histologically and by a significant reduction of colonic myeloperoxidase activity (P < 0·05).L. fermentumsignificantly counteracted the colonic glutathione depletion induced by the inflammatory process. In addition, both probiotics lowered colonic TNFα levels (P < 0·01) and inducible NO synthase expression when compared with non-treated rats; however, the decrease in colonic cyclo-oxygenase-2 expression was only achieved withL. fermentumadministration. Finally, the two probiotics induced the growth of Lactobacilli species in comparison with control colitic rats, but the production of SCFA in colonic contents was only increased whenL. fermentumwas given. In conclusion,L. fermentumcan exert beneficial immunomodulatory properties in inflammatory bowel disease, being more effective thanL. reuteri, a probiotic with reputed efficacy in promoting beneficial effects on human health.

scholarly journals High-fat diet promotes experimental colitis by inducing oxidative stress in the colon

2019 ◽  
Vol 317 (4) ◽  
pp. G453-G462 ◽  
Author(s):  
Xue Li ◽  
Xinzhi Wei ◽  
Yue Sun ◽  
Jie Du ◽  
Xin Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Fat Diet ◽  
Experimental Colitis ◽  
Mucosal Barrier ◽  
Mucosal Inflammation ◽  
High Fat ◽  
Trinitrobenzenesulfonic Acid ◽  
Barrier Permeability ◽  
Inflammatory Bowel ◽  
Colitis Model

Diets high in animal fats are associated with increased risks of inflammatory bowel disease, but the mechanism remains unclear. In this study, we investigated the effect of high-fat diet (HFD) on the development of experimental colitis in mice. Relative to mice fed low-fat diet (LFD), HFD feeding for 4 wk increased the levels of triglyceride, cholesterol, and free fatty acids in the plasma as well as within the colonic mucosa. In an experimental colitis model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS), mice on 4-wk HFD exhibited more severe colonic inflammation and developed more severe colitis compared with the LFD counterparts. HFD feeding resulted in higher production of mucosal pro-inflammatory cytokines, greater activation of the myosin light chain kinase (MLCK) tight junction regulatory pathway, and greater increases in mucosal barrier permeability in mice following TNBS induction. HFD feeding also induced gp91, an NADPH oxidase subunit, and promoted reactive oxygen species (ROS) production in both colonic epithelial cells and lamina propria cells. In HCT116 cell culture, palmitic acid or palmitic acid and TNF-α combination markedly increased ROS production and induced the MLCK pathway, and these effects were markedly diminished in the presence of a ROS scavenger. Taken together, these data suggest that HFD promotes colitis by aggravating mucosal oxidative stress, which rapidly drives mucosal inflammation and increases intestinal mucosal barrier permeability. NEW & NOTEWORTHY This study demonstrates high-fat diet feeding promotes colitis in a 2,4,6-trinitrobenzenesulfonic acid-induced experimental colitis model in mice. The underlying mechanism is that high-fat diet induces oxidative stress in the colonic mucosa, which increases colonic epithelial barrier permeability and drives colonic mucosal inflammation. These observations provide molecular evidence that diets high in saturated fats are detrimental to patients with inflammatory bowel diseases.

scholarly journals The sigma-1 receptor mediates the beneficial effects of pridopidine in a mouse model of Huntington disease

2017 ◽  
Vol 97 ◽  
pp. 46-59 ◽  
Author(s):  
Daniel Ryskamp ◽  
Jun Wu ◽  
Michal Geva ◽  
Rebecca Kusko ◽  
Iris Grossman ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington Disease ◽  
Sigma 1 Receptor ◽  
Beneficial Effects ◽  
Sigma 1

Experimental colitis in mice and sensitization of converging visceral and somatic afferent pathways

2006 ◽  
Vol 290 (3) ◽  
pp. G451-G457 ◽  
Author(s):  
Kenneth Lamb ◽  
Fang Zhong ◽  
G. F. Gebhart ◽  
Klaus Bielefeldt
Keyword(s):  
Experimental Colitis ◽  
The Body ◽  
Thermal Stimulation ◽  
Trinitrobenzenesulfonic Acid ◽  
Afferent Pathways ◽  
Colorectal Distension ◽  
Pain Syndromes ◽  
Response Thresholds ◽  
Frequent Micturition ◽  
Stimulation Of

Chronic pain syndromes affecting different organs often coexist. We hypothesized that sensitization of one afferent pathway may affect converging input from other areas of the body. We induced colitis in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS); control animals were treated with equal volumes of vehicle (50% ethanol) only. Visceromotor responses to graded colorectal distension, cystometrograms, and response thresholds to mechanical and thermal stimulation of both hind paws were determined on days 7 and 14. Inflammation of colon and bladder was assessed with validated histological markers and scores. TNBS caused significant colitis on day 7 that resolved by day 14; there was no evidence of bladder inflammation. There was a significant hypersensitivity to colorectal distension on day 7, which returned to normal on day 14. This was associated with bladder overactivity, as demonstrated by early onset of micturition and more frequent micturition on day 7 after TNBS administration. Colitis also significantly altered responses to mechanical and thermal stimulation of both hind paws on day 7 but not day 14. We conclude that cross talk between afferent visceral and somatic pathways may contribute to the coexistence of pain syndromes.

scholarly journals El entrenamiento de fuerza alivia las hipertrofias renal y cardíaca resultante de la hipertensión renovascular

2018 ◽  
Vol 0 (Avance Online) ◽  
Author(s):  
R Miguel-dos-Santos ◽  
JF Santos ◽  
FN Macedo ◽  
MB Almeida ◽  
VJ Santana-Filho ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cardiac Hypertrophy ◽  
Strength Training ◽  
Renovascular Hypertension ◽  
Reduce Blood Pressure ◽  
The Body ◽  
Male Rats ◽  
Left Renal Artery ◽  
Beneficial Effects

Resumo Objetivo: Avaliar os efeitos do treinamento de força sobre as hipertrofias renal e cardíaca induzida pela hipertensão renovascular em ratos. Método: Dezoito ratos Wistar foram divididos em três grupos: Sham, hipertenso (2K1C) e hipertenso treinado (2K1C-TR). Os animais foram induzidos a hipertensão renovascular através da ligadura da artéria renal esquerda. O treinamento de força foi iniciado quatro semanas após a indução da hipertensão renovascular, teve duração de 12 semanas e foi realizado a 70% de uma repetição máxima. Ao final foi medida pressão arterial, frequência cardíaca e parâmetros das hipertrofias renal e cardíaca. Resultados: O treinamento de força promoveu a redução da frequência cardíaca (p=0.0025) e da pressão arterial (p=0.01). Além disso, o treinamento diminuiu as massas absolutas do rim (p=0.0001) e coração (p=0.006), e os índices de hipertrofias renal e cardíaca, tanto normalizado pela massa corporal dos animais (p=0.0001 e p=0.001, respectivamente) como normalizado pelo comprimento da tíbia (p=0.004 e p=0.0004, respectivamente). Conclusão: O treinamento de força tem efeitos benéficos na hipertensão renovascular em animais, sendo capaz de reduzir a pressão arterial e a frequência cardíaca, além de atenuar o desenvolvimento das hipertrofias renal e cardíaca em ratos com hipertensão renovascular. Resumen Objetivo: Evaluar los efectos del entrenamiento de fuerza sobre las hipertrofias renal y cardíaca inducidas por la hipertensión renovascular en ratas. Método: Dieciocho ratas se dividieron en tres grupos: simulado, hipertenso (2R1C) e hipertenso entrenado (2R1C-TR). Los animales fueron inducidos a la hipertensión renovascular a través de la ligadura de la arteria renal izquierda. El entrenamiento de fuerza se inició cuatro semanas después de la inducción de la hipertensión renovascular, duró 12 semanas y se realizó al 70% de una repetición máxima. Al final se midió la presión arterial, la frecuencia cardiaca y los parámetros de las hipertrofias renal y cardíaca. Resultados: El entrenamiento de fuerza promovió la reducción de la frecuencia cardíaca (p=0.0025) y la presión arterial (p=0.01). Además el entrenamiento disminuyó las masas absolutas de los riñones (p=0.0001) y el corazón (p=0.006), y los índices de hipertrofias renal y cardíaca, tanto normalizado por la masa corporal de los animales (p=0.0001 e p=0.001, respectivamente) como normalizado por la longitud de la tibia (p=0.004 e p=0.0004, respectivamente). Conclusión: El entrenamiento de fuerza tiene efectos beneficiosos en la hipertensión renovascular en animales, siendo capaz de reducir la presión arterial y la frecuencia cardíaca, además de atenuar el desarrollo de las hipertrofias renal y cardíaca en ratas con hipertensión renovascular. Abstract Objective: To evaluate the effects of strength training on renal and cardiac hypertrophy induced by the renovascular hypertension in rats. Method: Eighteen male rats were divided into three groups: sham, hypertensive (2K1C) and trained hypertensive (2K1C-TR). The animals were induced to renovascular hypertension through ligation of the left renal artery. Strength training was initiated four weeks after the induction of renovascular hypertension, had the duration of 12 weeks and was performed at 70% of one maximum repetition. At the end, it was measured blood pressure, heart rate and parameters of renal and cardiac hypertrophies. Results: Strength training promoted reduction in heart rate (p=0.0025) and blood pressure (p=0.01). In addition, training decreased the absolute masses of the kidney (p=0.0001) and heart (p=0.006), and the indexes of renal and cardiac hypertrophy, both normalized by the body mass of the animals (p=0.0001 e p=0.001, respectively) and by the length of the tibia (p=0.004 e p=0.0004, respectively). Conclusion: Strength training has beneficial effects on renovascular hypertension in animals, being able to reduce blood pressure and heart rate, attenuating the development of renal and cardiac hypertrophies in rats with renovascular hypertension.

scholarly journals PPARγin Inflammatory Bowel Disease

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Vito Annese ◽  
Francesca Rogai ◽  
Alessia Settesoldi ◽  
Siro Bagnoli
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Potential Role ◽  
Intestinal Inflammation ◽  
Experimental Colitis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beneficial Effects ◽  
Inflammatory Bowel

Peroxisome proliferator-activated receptor gamma (PPARγ) is member of a family of nuclear receptors that interacts with nuclear proteins acting as coactivators and corepressors. The colon is a major tissue which expresses PPARγin epithelial cells and, to a lesser degree, in macrophages and lymphocytes and plays a role in the regulation of intestinal inflammation. Indeed, both natural and synthetic PPARγligands have beneficial effects in different models of experimental colitis, with possible implication in the therapy of inflammatory bowel disease (IBD). This paper will specifically focus on potential role of PPARγin the predisposition and physiopathology of IBD and will analyze its possible role in medical therapy.

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.

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