Myocardial protective effect by ulinastatin via an anti-inflammatory response after regional ischemia/reperfusion injury in an in vivo rat heart model

Shin, Il Woo; Jang, Inseok; Lee, Seung Min; Park, Kyeong Eon; Ok, Seong-Ho; Sohn, Ju-Tae; Lee, Heon Keun; Chung, Yoo Seung

doi:10.4097/kjae.2011.61.6.499

Cited by 28 publications

(23 citation statements)

References 21 publications

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“…In another study, it was also able inhibit NF-κB activity and alleviate live ischemia reperfusion injury (18). Furthermore, it was demonstrated to decrease the expression of TNF-α, IL-6, caspase-3 and thus reduced lipopolysaccharide/d-gal-induced acute liver damage (13) and myocardial ischemia reperfusion injury (14). A previous study by our group demonstrated that UTI improves renal fibrosis (19); however, the mechanism underlying this effect remained elusive.…”

Section: Discussionmentioning

confidence: 98%

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Ulinastatin attenuates renal interstitial inflammation and inhibits fibrosis progression in rats under unilateral ureteral obstruction

Jiang

Chen

et al. 2014

Molecular Medicine Reports

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Abstract. The aim of the present study was to examine the protective effects of the urinary trypsin inhibitor ulinastatin (UTI) on renal interstitial inflammation and fibrosis in rats subjected to unilateral ureteral obstruction (UUO). A total of 24 male Wistar rats were randomly divided into the three groups; the sham operation (SOR) group (n=8), the UUO group (n=8) and the UUO+UTI group (post-UUO UTI treatment, n=8). UUO was performed with complete ligation of the left ureter. As a medical intervention, saline (4 ml kg ) were injected, respectively, into the animals of the corresponding groups on day one following surgery. The rats in all three groups were euthanized on day seven post surgery. Blood samples were harvested for blood urea nitrogen (BUN) and serum creatinine (Scr) content measurements. The degree of interstitial pathological changes in the tissues from the obstructed kidneys were observed through hematoxylin and eosin (H&E) and Masson staining. The CD68+ macrophage amount, tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), nuclear factor-κB (NF-κB), transforming growth factor-β1 (TGF-β1) and type I collagen (Col-I) levels were examined immunohistochemically. The protein expression levels of NF-κB were examined using western blot analysis. Total superoxide dismutase (SOD) activity and malondialdehyde (MDA) content of homogenates were measured spectrophotometrically. The results revealed that ulinastatin had no statistically significant effect on the BUN and Scr levels (P>0.05). However, in comparison with the SOR group, the UUO group exhibited significantly more severe renal interstitial pathological injury in terms of tubular dilation, epithelial atrophy, renal interstitial inflammatory cell infiltration and proliferation of fibrous tissues, as well as significantly elevated levels of interstitial CD68+ macrophages, IL-1β, TNF-α, NF-κB, TGF-β1 and Col-I (P<0.01). UTI treatment significantly reduced UUO-induced renal interstitial damage with reduced levels of interstitial CD68+ macrophages, IL-1β, TNF-α, NF-κB, TGF-β1 and Col-I and MDA (P<0.05), and increased SOD levels (P<0.05).In conclusion, the present study indicated that UTI is able to effectively inhibit UUO-side renal interstitial inflammatory reaction and fibrosis in UUO-inflicted rats.

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Section: Discussionmentioning

confidence: 98%

“…Total (Cu-Zn and Mn) SOD (EC 1.15.1.1) activity was determined according to the method described by Shin et al (14). The principle of the method is based on the inhibition of nitroblue tetrazolium (NBT) reduction by the xanthine-xanthine oxidase system as a superoxide generator.…”

Section: Assessment Of Oxidative Stress [Lipid Peroxidation (Mda) Andmentioning

confidence: 99%

Ulinastatin attenuates renal interstitial inflammation and inhibits fibrosis progression in rats under unilateral ureteral obstruction

Jiang

Chen

et al. 2014

Molecular Medicine Reports

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“…Again, ulinastatin might have beneficial effects for relatively young and mildly ill patients, based on previous studies 5, 10, 13. Several animal and human studies reported that ulinastatin could have an organ‐protective effect 15, 29, 30. Hence, ulinastatin may work as “prevention” rather than “treatment” for organ dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Ulinastatin did not reduce mortality in elderly multiple organ failure patients: a retrospective observational study in a single center ICU

Uchida

Abe

Ono

et al. 2017

Acute Medicine & Surgery

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AimOur aim was to evaluate the effect of ulinastatin on 28‐day mortality in patients who developed multiple organ failure (MOF) related to their acute illness and were admitted to the intensive care unit (ICU).MethodsWe carried out a retrospective observational study of MOF patients in a general ICU of a tertiary care hospital in Japan from January 2009 to December 2012. The primary outcome was 28‐day all‐cause mortality. Secondary outcomes were ventilator‐free days, ICU‐free days, and vasopressor‐free days at day 28. We investigated the association between ulinastatin treatment and outcomes using multivariable regression analysis.ResultsA total of 212 MOF patients were included, 79 (37%) of whom received ulinastatin. The median age was 70 years (interquartile range, 60–77) and median APACHE II score was 25 (interquartile range, 19–29). Overall 28‐day mortality was 20%. There were no significant differences between the ulinastatin group and the control group in age, gender, or APACHE II score. The ulinastatin group had higher prevalence of sepsis (44% versus 22%, P = 0.001). Multivariable logistic regression analysis showed that ulinastatin was not associated with 28‐day mortality (odds ratio = 1.22; 95% confidence interval, 0.54–2.79). Moreover, ulinastatin did not reduce the mortality in patients with sepsis (odds ratio = 1.92; 95% confidence interval, 0.52–7.13). However, ICU‐free days and ventilator‐free days was significantly fewer in the ulinastatin group than control group.ConclusionsIn this retrospective observational study, ulinastatin was not associated with mortality in elderly patients with established MOF, although it might be related to patient's utility.

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“…As the advantages of urinary protease inhibitors, ulinastatin (UTI), such as improving organs ischemia/reperfusion, and anti-inflammatory effects, it is widely used in cardiac protection under the conditions of cardiopulmonary resuscitation, heart failure and the others [1][2][3][4][5]. However, clinically, the myocardial protective effect of UTI is not obvious at low dosage level.…”

Section: Introductionmentioning

confidence: 99%

The protection effects of different dosages of ulinastatin on myocardial

Ling¹,

Sun²

2016

Integr Mol Med

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The aim is to explore the protection effect of ulinastatin (UTI) on myocardial in different dosages and its mechanism. From May to August 2014, in the animal laboratory of the 309th hospital of PLA, the experiment was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals for the National Institutes of Health. The animal protocol was approved by the Institutional Animal Care Committee of the 309th Hospital of PLA (Permit Number: 13-269). 120 SD rats were randomly divided into control group (treated with normal saline), UTI low-dose group (30000 IU/kg), UTI moderate-dose group (60000 IU/kg) and high-dose group (90000 IU/kg). All rats were treated with UTI for 2 weeks via vein. Then left ventricular end diastolic diameter (LVEDD), left ventricular endsystolic dimension (LVESD) and left ventricular ejection fraction (LVEF) were employed to evaluate heart function. Hyp determination with chloramine-T oxidation method was employed to detect the myocardial fibrosis degree, while brain natriuretic peptide (BNP) was used to assess heart function. By comparison among groups, the results of the high-dose group were better than that of any other group in LVEDD, LVESD, LVEF, BNP content, as well as in heart function.It is better for myocardial protection with high-dose of ulinastatin, the possible mechanism is relevant to inhibit myocardial interstitial fibrosis and ventricular remodeling.

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Myocardial protective effect by ulinastatin via an anti-inflammatory response after regional ischemia/reperfusion injury in an in vivo rat heart model

Cited by 28 publications

References 21 publications

Ulinastatin attenuates renal interstitial inflammation and inhibits fibrosis progression in rats under unilateral ureteral obstruction

Ulinastatin attenuates renal interstitial inflammation and inhibits fibrosis progression in rats under unilateral ureteral obstruction

Ulinastatin did not reduce mortality in elderly multiple organ failure patients: a retrospective observational study in a single center ICU

The protection effects of different dosages of ulinastatin on myocardial

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