Chronic lithium administration ameliorates 2,4,6‐trinitrobenzene sulfonic acid‐induced colitis in rats; potential role for adenosine triphosphate sensitive potassium channels

Daneshmand, Ali; Mohammadi, Hamed; Rahimian, Reza; Habibollahi, Peiman; Fakhfouri, Gohar; Talab, Saman Shafat; Mehr, Shahram Ejtemaei; Dehpour, Ahmad Reza

doi:10.1111/j.1440-1746.2011.06719.x

Cited by 28 publications

(18 citation statements)

References 44 publications

(65 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For instance, geniposide has been used for the amelioration of spontaneously obese type 2 diabetic mice and has been shown to suppress body weight and visceral fat accumulation [36] . Inflammatory cytokine release and neutrophil infiltration play an important role in colitis; MPO can indirectly reflect the vitality of neutrophil infiltration [37] . NF-κB, an important regulatory factor of inflammation, regulates the expression of genes that are involved in the production of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6 [38] .…”

Section: Discussionmentioning

confidence: 99%

Geniposide ameliorates TNBS-induced experimental colitis in rats via reducing inflammatory cytokine release and restoring impaired intestinal barrier function

et al. 2017

Acta Pharmacol Sin

View full text Add to dashboard Cite

Geniposide is an iridoid glycosides purified from the fruit of Gardenia jasminoides Ellis, which is known to have antiinflammatory, antioxidative and anti-tumor activities. The present study aimed to investigate the effects of geniposide on experimental rat colitis and to reveal the related mechanisms. Experimental rat colitis was induced by rectal administration of a TNBS solution. The rats were treated with geniposide (25, 50 mg·kg, ig) or with sulfasalazine (SASP, 100 mg·kg, ig) as positive control for 14 consecutive days. A Caco-2 cell monolayer exposed to lipopolysaccharides (LPS) was used as an epithelial barrier dysfunction model. Transepithelial electrical resistance (TER) was measured to evaluate intestinal barrier function. In rats with TNBS-induced colitis, administration of geniposide or SASP significantly increased the TNBS-decreased body weight and ameliorated TNBS-induced experimental colitis and related symptoms. Geniposide or SASP suppressed inflammatory cytokine (TNF-α, IL-1β, and IL-6) release and neutrophil infiltration (myeloperoxidase activity) in the colon. In Caco-2 cells, geniposide (25-100 μg/mL) ameliorated LPS-induced endothelial barrier dysfunction via dose-dependently increasing transepithelial electrical resistance (TER). The results from both in vivo and in vitro studies revealed that geniposide down-regulated NF-κB, COX-2, iNOS and MLCK protein expression, up-regulated the expression of tight junction proteins (occludin and ZO-1), and facilitated AMPK phosphorylation. Both AMPK siRNA transfection and AMPK overexpression abrogated the geniposide-reduced MLCK protein expression, suggesting that geniposide ameliorated barrier dysfunction via AMPKmediated inhibition of the MLCK pathway. In conclusion, geniposide ameliorated TNBS-induced experimental rat colitis by both reducing inflammation and modulating the disrupted epithelial barrier function via activating the AMPK signaling pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Geniposide ameliorates TNBS-induced experimental colitis in rats via reducing inflammatory cytokine release and restoring impaired intestinal barrier function

et al. 2017

Acta Pharmacol Sin

View full text Add to dashboard Cite

show abstract

“…This question could be explored with glibenclamide, as it restores TNF-α-induced dysfunction. However, reports show that this blocker leads to increased severity of experimental IBD [21,75] and that the opening of K ATP channels has anti-inflammatory effects by suppressing the production of pro-inflammatory cytokines such as TNF-α and IL-1β in the gut [18,32]. …”

Section: Discussionmentioning

confidence: 99%

The pro‐inflammatory cytokineTNF‐α inhibits lymphatic pumping via activation of theNF‐κB‐iNOSsignaling pathway

et al. 2017

View full text Add to dashboard Cite

Objective Mesenteric lymphatic vessels pumping, important to propel lymph and immune cells from the intestinal interstitium to the mesenteric lymph nodes, is compromised during intestinal inflammation. The objective of this study was to test the hypothesis that the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α), is a significant contributor to the inflammation-induced lymphatic contractile dysfunction, and to determine its mode of action. Methods Contractile parameters were obtained form isolated rat mesenteric lymphatic vessels mounted on a pressure myograph after 24-h incubation with or without TNF-α. Various inhibitors were administered and quantitative real-time PCR, western blotting and immunofluorescence confocal imaging were applied to characterize the mechanisms involved in TNF-α actions. Results Vessel contraction frequency was significantly decreased after TNF-α treatment and could be restored by selective inhibition of NF-кB, iNOS, guanylate cyclase and ATP-sensitive K+ channels. We further demonstrated that NF-кB inhibition also suppressed the significant increase in iNOS mRNA observed in TNF-α-treated lymphatic vessels and that TNF-α treatment favor the nuclear translocation of the p65 NF-κB subunit. Conclusions These findings suggest that TNF-α decreases mesenteric lymphatic contractility by activating the NF-κB - iNOS signaling pathway. This mechanism could contribute to the alteration of lymphatic pumping reported in intestinal inflammation.

show abstract

“…Besides, high K ϩ secretion could explain hypokalemia observed in severe cases of UC (116). Epithelial K ATP channels, as abovementioned, have not been specifically studied yet, but glibenclamide worsens colitis (35,42) and nicorandil has been proposed for the management of IBD (60). Interestingly, monochloramine (NH 2 Cl) increased basolateral Ca 2ϩ -dependent K ϩ conductance and NKA activity in healthy rat colonic epithelia and T84 cells, suggesting that it may contribute to diarrhea in IBD due to increased anion secretion rather than low sodium absorption (121, 133).…”

Section: Role Of Epithelial K ϩ Channelsmentioning

confidence: 99%

“…However, these results were attributed to the inhibition of lymphocytic, and not IEC, channels. K ATP channels do play a role in IBD since the blocker glibenclamide worsens colitis (35,42) whereas sildenafil (42), nicorandil (60) and H 2 S (140) have beneficial effects on this condition, but intestinal epithelial K ATP channels need further research before they can be considered therapeutic targets. Finally, it would be of high interest to test IEC BK channel blockers or inhibitors [multiple examples can be found in the review by Nardi and Olesen (101)] in experimental colitis models.…”

Section: Therapeutic Targets and Future Challengesmentioning

confidence: 99%

Role of epithelial ion transports in inflammatory bowel disease

Magalhães

Cabral

Soares‐da‐Silva

et al. 2016

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with a complex pathogenesis. Diarrhea is a highly prevalent and often debilitating symptom of IBD patients that results, at least in part, from an intestinal hydroelectrolytic imbalance. Evidence suggests that reduced electrolyte absorption is more relevant than increased secretion to this disequilibrium. This systematic review analyses and integrates the current evidence on the roles of epithelial Na+-K+-ATPase (NKA), Na+/H+ exchangers (NHEs), epithelial Na+ channels (ENaC), and K+ channels (KC) in IBD-associated diarrhea. NKA is the key driving force of the transepithelial ionic transport and its activity is decreased in IBD. In addition, the downregulation of apical NHE and ENaC and the upregulation of apical large-conductance KC all contribute to the IBD-associated diarrhea by lowering sodium absorption and/or increasing potassium secretion.

show abstract

Chronic lithium administration ameliorates 2,4,6‐trinitrobenzene sulfonic acid‐induced colitis in rats; potential role for adenosine triphosphate sensitive potassium channels

Abstract: Lithium exerts prominent anti-inflammatory effects on TNBS-induced colitis in rats. Potassium channels contribute to these beneficial properties.

Cited by 28 publications

References 44 publications

Geniposide ameliorates TNBS-induced experimental colitis in rats via reducing inflammatory cytokine release and restoring impaired intestinal barrier function

Geniposide ameliorates TNBS-induced experimental colitis in rats via reducing inflammatory cytokine release and restoring impaired intestinal barrier function

The pro‐inflammatory cytokineTNF‐α inhibits lymphatic pumping via activation of theNF‐κB‐iNOSsignaling pathway

Role of epithelial ion transports in inflammatory bowel disease

Contact Info

Product

Resources

About