Urinary trypsin inhibitor suppresses excessive generation of superoxide anion radical, systemic inflammation, oxidative stress, and endothelial injury in endotoxemic rats

Tanaka, Ryo; Fujita, Motoki; Tsuruta, Ryosuke; Fujimoto, Kenji; Aki, Hiromi Shinagawa; Kumagai, Kazumi; Aoki, Tetsuya; Kobayashi, Akihiro; Izumi, Takeki; Kasaoka, Shunji; Yuasa, Makoto; Maekawa, Taira

doi:10.1007/s00011-010-0166-8

Cited by 31 publications

(27 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, previous studies have demonstrated that UTI suppresses the elevation of IL-6 and IL-8 levels in patients undergoing coronary artery bypass grafting under extracorporeal circulation (18), alleviates forebrain I/R injury by inhibiting the production of superoxide radicals and intercellular adhesion molecule-1 (19) and improves oleic acid-induced acute lung injury by reducing TNF-α levels and inducing leukocyte activation (20). In addition, UTI has been proposed as a therapeutic option for endotoxin-associated inflammatory disorders, including acute lung and liver injuries (21), due to its anti-inflammatory properties (22)(23)(24). However, whether UTI protects against brain injury by inhibiting the inflammatory responses following CA is yet to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Postconditioning improvement effects of ulinastatin on brain injury following cardiopulmonary resuscitation

Sui

2014

Exp Ther Med

View full text Add to dashboard Cite

Abstract. The aim of the present study was to determine the effects of ulinastatin (UTI) on brain injury in rats subjected to cardiopulmonary resuscitation (CPR) following asphyxial cardiac arrest (CA) and identify the underlying mechanisms. In total, 100 healthy male Wistar rats were randomly divided into control and treatment groups (n=50). After 4 min of asphyxial CA, all the rats were immediately subjected to CPR. The treatment group animals were administered 15 mg/kg UTI at the onset of resuscitation. The mortality rate in the two groups was recorded at 24 h post-resuscitation. In addition, neurological function was evaluated at 24, 48 and 72 h post-resuscitation using a neurological deficit scale (NDS). Furthermore, the effects of UTI on the Toll-like receptor 4 (TLR4) signaling pathway in brain tissues were determined by assessing TLR4 mRNA expression, nuclear factor (NF)-κB activity and tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels at 1, 3, 6, 12, 24, 48 and 72 h post-resuscitation. After 24 h, the mortality rate significantly decreased in the treatment group when compared with the control animals (10 vs. 30%; P<0.05). Additionally, an overt improvement was observed in the NDS score following UTI treatment when compared with the control (P<0.01). Finally, statistically significant decreases in the levels of TLR4 mRNA expression, NF-κB activity and TNF-α and IL-6 were observed in the treatment group at each time point (P<0.01). Therefore, UTI treatment at the onset of CPR significantly inhibits the TLR4 signaling pathway, thereby alleviating the inflammatory responses following resuscitation and improving neurological function.

show abstract

Section: Discussionmentioning

confidence: 99%

Postconditioning improvement effects of ulinastatin on brain injury following cardiopulmonary resuscitation

Sui

2014

Exp Ther Med

View full text Add to dashboard Cite

show abstract

“…Kobayashi et al observed that UTI inhibited tumor invasion and metastasis, possibly through the suppression of cell-associated plasmin activity and the mRNA and protein expression of urokinase plasminogen (uPA). In endotoxemic rats, UTI suppresses excessive superoxide (O 2 -) generation, systemic inflammation, lipid peroxidation and HMGB1 (33). However, the potential role of UTI in the regulation of HMGB1 in cancer remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Effect of ulinastatin on the expression and distribution of high mobility group box 1 in human colon carcinoma cells in vitro

Wang

Tao

Dong

et al. 2014

Molecular Medicine Reports

View full text Add to dashboard Cite

Abstract. The aim of the present study was to investigate the in vitro effects of ulinastatin (UTI) on the proliferation, invasion, apoptosis, expression and distribution of high mobility group box 1 (HMGB1) and the expression of nuclear factor κB (NF-κB) in human colon carcinoma LoVo cells. The cells were divided into control (untreated), UTI1 (400 U/ml UTI), UTI2 (800 U/ml UTI) and UTI3 (1,600 U/ml UTI) groups. The cell proliferation, invasion, apoptosis and the gene and protein expression of HMGB1 and NF-κB were detected using a tetrazolium assay, Transwell cell invasion assays, a caspase-3 activity assay, western blot analysis and reverse transcription quantitative polymerase chain reaction, respectively. The distribution of HMGB1 was detected using immunofluorescence. LoVo cell proilferation decreased the most in the UTI3 group followed, in order, by the UTI2, UTI1 and control groups. UTI inhibited invasion in LoVo cells and the inhibitory effect was enhanced as the UTI concentration increased. The activity of caspase-3 increased the least in the control group followed, in order, by the UTI1, UTI2 and UTI3 groups. UTI inhibited the expression of HMGB1 and NF-κB, and decreased the cytoplasmic distribution of HMGB1. Thus, UTI inhibited LoVo cell proliferation and induced LoVo cell apoptosis, the mechanism of which may be associated with a decreased in the expression of HMGB1 and NF-κB, and the cytoplasmic distribution of HMGB1.

show abstract

“…Following activating of macrophage, neutrophils, NADPH oxidase is activated, leading to excessive ROS generation to kill the bacteria. Of course, one coin two sides, at the sometime ROS also injuries lung tissue and lead to breathlessness, and then enhance SIRS (Tanaka et al 2010). Japanese scholars found out the level of O 2 -, HMGB1, TNF-a, IL-6 were lower in UTI treatment group than the control group (Tanaka et al 2010).…”

Section: Decrease the Production Of Omentioning

confidence: 99%

“…Of course, one coin two sides, at the sometime ROS also injuries lung tissue and lead to breathlessness, and then enhance SIRS (Tanaka et al 2010). Japanese scholars found out the level of O 2 -, HMGB1, TNF-a, IL-6 were lower in UTI treatment group than the control group (Tanaka et al 2010). Previous studies had shown that the expression of HMGB1, TNF-a, IL-6 was regulated by NF-κB.…”

Section: Decrease the Production Of Omentioning

confidence: 99%

Ulinastatin and Septic Cardiac Dysfunction

Lin¹,

Lin²

2012

The Transmission Electron Microscope

View full text Add to dashboard Cite

Urinary trypsin inhibitor suppresses excessive generation of superoxide anion radical, systemic inflammation, oxidative stress, and endothelial injury in endotoxemic rats

Abstract: UTI suppressed excessive O(2)(-*) generation, systemic inflammation, lipid peroxidation, and endothelial injury in endotoxemic rats.

Cited by 31 publications

References 46 publications

Postconditioning improvement effects of ulinastatin on brain injury following cardiopulmonary resuscitation

Postconditioning improvement effects of ulinastatin on brain injury following cardiopulmonary resuscitation

Effect of ulinastatin on the expression and distribution of high mobility group box 1 in human colon carcinoma cells in vitro

Ulinastatin and Septic Cardiac Dysfunction

Contact Info

Product

Resources

About