Effect of bilirubin in ischemia/reperfusion injury on rat small intestine

Ceran, Candemir; Sönmez, Kaan; Türkyılmaz, Zafer; Demiroğullarι, Billur; Dursun, Ayşe; Düzgün, Ersel; Başaklar, A. Can; Kale, Nuri

doi:10.1053/jpsu.2001.28816

Cited by 48 publications

(32 citation statements)

References 19 publications

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“…This bilirubin acts as an antioxidant capable of scavenging peroxy radicals and inhibiting lipid peroxidation. It has been demonstrated that exogenous treatment with bilirubin provides in vitro protection against oxidative stress and hypoxia in mammalian cell culture and in vivo protection against ischemia in the rat heart (Clark et al 2000) and intestine (Ceran et al 2001). In addition, CO, another product of heme catabolism, showed a number of cytoprotective functions during various conditions of oxidative stress, including hyperoxic lung injury, endotoxemia, and graft rejection of the liver, heart, and lung .…”

Section: Discussionmentioning

confidence: 99%

Evidence that Cisplatin-induced Auditory Damage is Attenuated by Downregulation of Pro-inflammatory Cytokines Via Nrf2/HO-1

Kim

et al. 2008

JARO

111

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Recently, we demonstrated that pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 played a critical role in cisplatin-induced cochlear injury and that flunarizine, known as a T-type Ca 2+ channel antagonist, induced a cytoprotective effect against cisplatin cytotoxicity in HEI-OC1 cells by the activation of NF-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) cascade through PI3K-Akt signaling but calciumindependent pathway. We report here that flunarizine markedly attenuates cisplatin-induced pro-inflammatory cytokine secretion and their messenger RNA transcription as well as cisplatin cytotoxicity through the activation of Nrf2/HO-1 and downregulation of NF-κB. In HEI-OC1 cells, overexpression of Nrf2/HO-1 by gene transfer or pharmacological approaches attenuated cisplatin-induced cytotoxicity and proinflammatory cytokine production. On the contrary, inhibition of Nrf2/HO-1 signaling by pharmacological inhibitors or specific small interfering RNAs significantly abolished the beneficial effects of flunarizine. Flunarizine also attenuated cisplatin-mediated MAPK activation and pharmacological inhibition of MAPKs, especially MEK1/ERK, blocked cisplatin-induced NF-κB activation in HEI-OC1 cells. Furthermore, WT-Nrf2 overexpression effectively blocked MAPK activation after cisplatin exposure. Finally, orally administrated Sibelium™, the trade name of flunarizine, suppressed the increase of pro-inflammatory cytokines by cisplatin in both serum and cochleas of mice, whereas it increased HO-1 expression in cochleas. These results indicate that flunarizine induces a protective effect against cisplatin ototoxicity through the downregulation of NF-κB by Nrf2/HO-1 activation and the resulting inhibition of pro-inflammatory cytokine production in vitro and in vivo.

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Section: Discussionmentioning

confidence: 99%

Evidence that Cisplatin-induced Auditory Damage is Attenuated by Downregulation of Pro-inflammatory Cytokines Via Nrf2/HO-1

Kim

et al. 2008

JARO

111

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“…Biliverdin (Frontier Scientific; Logan, UT) was dissolved in 0.1 N NaOH and adjusted to a final pH of 7.4 with HCl. After a dilution in PBS, 5 mg/kg biliverdin was injected intraperitoneally 8,6, and 3 h before laparotomy, again just before closure of the laparotomy, and then 15 h postoperatively for motility studies. Sham control animals were given appropriate saline volumes at the same time points intraperitoneally.…”

Section: Methodsmentioning

confidence: 99%

“…However, this view changed dramatically when biliverdin/bilirubin were found to be potent antioxidants (40,43,50). The effectiveness of this HO-1 end product has been demonstrated in numerous inflammatory models [inflammatory bowel disease, intestinal ischemia-reperfusion, allogeneic transplantation, and acetaminophen-induced hepatotoxicity (8,9,19,43)]. However, a potential beneficial effect of biliverdin/ bilirubin in sepsis has not previously been investigated.…”

mentioning

confidence: 99%

Biliverdin protects against polymicrobial sepsis by modulating inflammatory mediators

Overhaus¹,

Moore²,

Barbato³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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Highly inducible heme oxygenase (HO)-1 is protective against acute and chronic inflammation. HO-1 generates carbon monoxide (CO), ferrous iron, and biliverdin. The aim of this study was to investigate the protective effects of biliverdin against sepsis-induced inflammation and intestinal dysmotility. Cecal ligation and puncture (CLP) was performed on Sprague-Dawley rats under isoflurane anesthesia with and without intraperitoneal biliverdin injections, which were done before, at the time of CLP, and after CLP. In vivo gastrointestinal transit was carried out with fluorescein-labeled dextran. Jejunal circular muscle contractility was quantified in vitro using organ bath-generated bethanechol dose-response curves. Neutrophilic infiltration into the muscularis externa was quantified. The jejunal muscularis was studied for cytokine mRNA expressions [interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, inducible nitric oxide synthase, cyclooxygenase-2, biliverdin, IL-10, and HO-1] using real-time RT-PCR. Biliverdin treatment prevented the sepsis-induced suppression of gastrointestinal muscle contractility in vivo and in vitro and significantly decreased neutrophilic infiltration into the jejunal muscularis. Inflammatory mRNA expressions for small bowel IL-6 and MCP-1 were significantly reduced after biliverdin treatment in CLP-induced septic animals compared with untreated septic animals. The anti-inflammatory mediator expression of small bowel IL-10 was significantly augmented after CLP at 3 h compared with untreated septic animals. These findings demonstrate that biliverdin attenuates sepsis-induced morbidity to the intestine by selectively modulating the inflammatory cascade and its subsequent sequelae on intestinal muscularis function.

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“…17,18 In this study, blood MDA level was used to determine the severity of the I/R injury. We found a direct correlation between blood MDA levels and histopathologic injury grade, which is an objective indicator of the status of the mucosal barrier.…”

Section: Discussionmentioning

confidence: 99%

Effects of trapidil on intestinal mucosal barrier function and bacterial translocation after intestinal ischemia and reperfusion in an experimental rat model

Çolak¹,

Öztürk²,

Polat

et al. 2003

Current Therapeutic Research

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Background: Intestinal ischemia and reperfusion may be the primary triggers of mucosal barrier impairment, cytokine expression, and bacterial translocation (BT). Trapidil is a phosphodiesterase and platelet-derived growth factor inhibitor that reduces lipid peroxidation and inhibits the production of cytokines.Objective: The goal of this study was to assess whether trapidil might protect the intestinal epithelial barrier by inhibiting lipid peroxidation and proinflammatory cytokines by testing the effect of trapidil on intestinal barrier function in an experimental ischemia/reperfusion (I/R) rat model.Methods: Trapidil was used in a rat model of intestinal barrier dysfunction caused by intestinal ischemia for 40 minutes followed by reperfusion for 12 hours. To do this, the rats were randomized

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Effect of bilirubin in ischemia/reperfusion injury on rat small intestine

Cited by 48 publications

References 19 publications

Evidence that Cisplatin-induced Auditory Damage is Attenuated by Downregulation of Pro-inflammatory Cytokines Via Nrf2/HO-1

Evidence that Cisplatin-induced Auditory Damage is Attenuated by Downregulation of Pro-inflammatory Cytokines Via Nrf2/HO-1

Biliverdin protects against polymicrobial sepsis by modulating inflammatory mediators

Effects of trapidil on intestinal mucosal barrier function and bacterial translocation after intestinal ischemia and reperfusion in an experimental rat model

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