Selected biochemical parameters and ultrastructural picture of pancreas due to Ulinastatin treatment of experimental acute pancreatitis

Maciejewski, Ryszard; Burdan, Franciszek; Burski, K; Madej, B; Ziemiakowicz, R; Dabrowski, A; Wallner, Grzegorz

doi:10.1016/j.etp.2004.09.001

Cited by 9 publications

(6 citation statements)

References 33 publications

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“…It is frequently used clinically for the treatment of shock (33) and acute pancreatitis (34). According to the pharmaceutical reference of UTI, side-effects have been reported in 74/8,710 patients (0.8%) at doses up to of 3×10 5 U/day (32).…”

Section: Discussionmentioning

confidence: 99%

Ulinastatin post-treatment attenuates lipopolysaccharide-induced acute lung injury in rats and human alveolar epithelial cells

Luo

Che

Zhao

2016

International Journal of Molecular Medicine

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Ulinastatin (UTI), a serine protease inhibitor, possesses anti-inflammatory properties and has been suggested to modulate lipopolysaccharide (LPS)-induced acute lung injury (ALI). High-mobility group box 1 (HMGB1), a nuclear DNA-binding protein, plays a key role in the development of ALI. The aim of this study was to investigate whether UTI attenuates ALI through the inhibition of HMGB1 expression and to elucidate the underlying molecular mechanisms. ALI was induced in male rats by the intratracheal instillation of LPS (5 mg/kg). UTI was administered intraperitoneally 30 min following exposure to LPS. A549 alveolar epithelial cells were incubated with LPS in the presence or absence of UTI. An enzyme-linked immunosorbent assay was used to detect the levels of inflammatory cytokines. Western blot analysis was performed to detect the changes in the expression levels of Toll-like receptor 2/4 (TLR2/4) and the activation of nuclear factor-κB (NF-κB). The results revealed that UTI significantly protected the animals from LPS-induced ALI, as evidenced by the decrease in the lung wet to dry weight ratio, total cells, neutrophils, macrophages and myeloperoxidase activity, associated with reduced lung histological damage. We also found that UTI post-treatment markedly inhibited the release of HMGB1 and other pro-inflammatory cytokines. Furthermore, UTI significantly inhibited the LPS-induced increase in TLR2/4 protein expression and NF-κB activation in lung tissues. In vitro, UTI markedly inhibited the expression of TLR2/4 and the activation of NF-κB in LPS-stimulated A549 alveolar epithelial cells. The findings of our study indicate that UTI attenuates LPS-induced ALI through the inhibition of HMGB1 expression in rats. These benefits are associated with the inhibition of the activation of the TLR2/4-NF-κB pathway by UTI.

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Section: Discussionmentioning

confidence: 99%

Ulinastatin post-treatment attenuates lipopolysaccharide-induced acute lung injury in rats and human alveolar epithelial cells

Luo

Che

Zhao

2016

International Journal of Molecular Medicine

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“…Urinary trypsin inhibitors have been used to treat pancreatitis, septic shock and hemorrhagic shock (29–31). Chen et al (32) reported that the protective effects of ulinastatin may be associated with the upregulation of Bcl-2, an inhibitor of cell apoptosis, in a hemorrhagic shock animal model.…”

Section: Discussionmentioning

confidence: 99%

Ulinastatin inhibits cerebral ischemia-induced apoptosis in the hippocampus of gerbils

CHO

Shin

et al. 2015

Molecular Medicine Reports

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Ulinastatin is a urinary trypsin inhibitor, originally extracted and purified from human urine. Ulinastatin has cytoprotective effects against ischemic injury in several organs. In the present study, the neuroprotective effects of ulinastatin following ischemic cerebral injury in the hippocampus of gerbils was investigated. To induce transient global ischemia in gerbils, the common carotid arteries were occluded using aneurysm clips for 5 min, and the clips were then removed. Ulinastatin was subcutaneously injected into the gerbils once a day for 7 days at doses of 50,000 or 100,000 U/kg. The gerbils were confronted with a step-down avoidance task, following which tissue samples from the gerbils were examined using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, western blot analysis for B-cell lymphoma (Bcl-2) and Bcl-2-associated X protein (Bax), immunohistochemistry for caspase-3 and immunofluorescence for 5-bromo-2′-deoxyuridine. The numbers of TUNEL-positive and caspase-3-positive cells in the hippocampal CA1 region increased following cerebral ischemia. The expression of Bax in the hippocampus increased, while the expression of Bcl-2 in the hippocampus decreased following cerebral ischemia. These results confirmed that apoptosis in the hippocampus was enhanced following cerebral ischemia in gerbils. The levels of cell proliferation in the hippocampal dentate gyrus were also enhanced by ischemia, which is possibly an adaptive mechanism to compensate for excessive levels of apoptosis. Ulinastatin treatment inhibited ischemia-induced apoptosis by suppressing apoptosis-associated molecules, and thus ameliorated ischemia-induced short-term memory impairment. The cell proliferation in the hippocampus was also suppressed following ulinastatin treatment. These results suggested the use of ulinastatin as a therapeutic agent for patients with cerebral stroke.

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“…In an experimental diabetic animal model, the PNLIP activity correlated with the development of diabetes [10]. Therefore, alterations in the function and/or expression of the CLPS and/or PNLIP could be responsible, in part, for individual variation in lipid metabolism or other risk factors contributing to type 2 diabetes mellitus.…”

Section: Introductionmentioning

confidence: 98%

Putative association between a new polymorphism in exon 3 (Arg109Cys) of the pancreatic colipase gene and type 2 diabetes mellitus in two independent Caucasian study populations

Lindner

Helwig

Rubin

et al. 2005

Mol. Nutr. Food Res.

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The protein encoded by the pancreatic colipase (CLPS) gene is an essential cofactor needed by pancreatic triglyceride lipase (PNLIP) for efficient dietary lipid hydrolysis. Since the inhibition of lipase activity was shown to reduce the incidence of type 2 diabetes mellitus, we tested the hypothesis that genetic variations in the CLPS and PNLIP genes are associated with type 2 diabetes; 47 unrelated subjects were screened for polymorphisms of the CLPS and PNLIP genes. A nested-case control study of 192 incident type 2 diabetes subjects and 384 sex- and age-matched controls taken from the European Prospective Investigation into Cancer and Nutrition Potsdam Cohort (EPIC) was employed for association studies. The Metabolic Intervention Cohort Kiel (MICK) consisting of 716 males was used for verification. A novel putative functional polymorphism (Arg109Cys) was identified in the CLPS gene. The frequencies of the Arg/Cys genotype were 2.6% in EPIC and 2.2% in MICK study subjects. No homozygotes for the Cys/Cys genotype were found in either study population. Logistic regression analysis showed a statistically significant association of the Arg/Cys genotype with an increased risk of type 2 diabetes. The odds ratios estimated by the model were 3.75 (95%CI = 1.13-12.49, p = 0.03) in EPIC and 4.86 (95%CI = 1.13-20.95, p = 0.03) in MICK. No comparable associations were found with other traits of the insulin-resistance syndrome (e. g.; body mass index, waist to hip ratio). In conclusion, we obtained evidence in two German Caucasian study populations that the variant of the rare CLPS Arg109Cys polymorphism might contribute to increased susceptibility of type 2 diabetes.

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Selected biochemical parameters and ultrastructural picture of pancreas due to Ulinastatin treatment of experimental acute pancreatitis

Cited by 9 publications

References 33 publications

Ulinastatin post-treatment attenuates lipopolysaccharide-induced acute lung injury in rats and human alveolar epithelial cells

Ulinastatin post-treatment attenuates lipopolysaccharide-induced acute lung injury in rats and human alveolar epithelial cells

Ulinastatin inhibits cerebral ischemia-induced apoptosis in the hippocampus of gerbils

Putative association between a new polymorphism in exon 3 (Arg109Cys) of the pancreatic colipase gene and type 2 diabetes mellitus in two independent Caucasian study populations

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