The effects of a new human leukocyte elastase inhibitor (recombinant guamerin) on cerulein-induced pancreatitis in rats

Jo, Yun Ju; Choi, Ho Soon; Jun, Dae Won; Lee, Oh Young; Kang, Joo Seop; Park, Il Gyu; Jung, Kyung‐Hoon; Hahm, Joon Soo

doi:10.1016/j.intimp.2008.02.014

Cited by 9 publications

(11 citation statements)

References 33 publications

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“…The potential of ulinastatin in treating pancreatitis has been demonstrated extensively in conditions such as post‐endoscopic retrograde cholangiopancreatography pancreatitis, experimental acute pancreatitis, and chronic pancreatitis . In addition to blocking proteases, there is growing evidence that ulinastatin might play a role in preventing progressive inflammation of the pancreas, irrespective of the associated cause …”

Section: Introductionmentioning

confidence: 99%

“…10 In addition to blocking proteases, there is growing evidence that ulinastatin might play a role in preventing progressive inflammation of the pancreas, irrespective of the associated cause. [10][11][12] Previous in vivo studies have shown that ulinastatin can inhibit the expression of nuclear factor-κB (NF-κB), 13 tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), 8 and increase the levels of IL-2, IL-10, and interferon-γ. 9 These cytokines play important roles in the initiation and amplification of inflammatory responses during pancreatitis.…”

Section: Introductionmentioning

confidence: 99%

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Ulinastatin activates the renin–angiotensin system to ameliorate the pathophysiology of severe acute pancreatitis

Liu

Wang

et al. 2014

J of Gastro and Hepatol

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ulinastatin activates the renin–angiotensin system to ameliorate the pathophysiology of severe acute pancreatitis

Liu

Wang

et al. 2014

J of Gastro and Hepatol

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“…However, to our knowledge no previous investigations using this rat model of caeruleininduced AP have examined plasma and BAL TNF-α levels. Caerulein infusion rat studies have examined TNF-α levels in plasma but only at early points and demonstrated increases between 6 and 8 hours [34,35] and resolution by 12 hours [36]. This suggests a possible biphasic profile, as our findings demonstrate that plasma TNF-α concentration also appears to increase between 96 In the context of AP, activation and migration of circulating leukocytes to the lungs are required to induce damage important in the development of ARDS [10].…”

Section: Experimental Lung Researchmentioning

confidence: 65%

Caerulein-induced acute pancreatitis results in mild lung inflammation and altered respiratory mechanics

Elder

Saccone

Bersten

et al. 2010

Experimental Lung Research

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Acute lung injury is a common complication of acute pancreatitis (AP) and contributes to the majority of AP-associated deaths. Although some aspects of AP-induced lung inflammation have been demonstrated, investigation of resultant changes in lung function is limited. The aim of this study was to characterize lung injury in caerulein-induced AP. Male Sprague Dawley rats (n = 7-8/group) received 7 injections of caerulein (50 μg/kg) at 12, 24, 48, 72, 96, or 120 hours before measurement of lung impedance mechanics. Bronchoalveolar lavage (BAL), plasma, pancreatic, and lung tissue were collected to determine pancreatic and lung measures of acute inflammation. AP developed between 12 and 24 hours, as indicated by increased plasma amylase activity and pancreatic myeloperoxidase (MPO) activity, edema, and abnormal acinar cells, before beginning to resolve by 48 hours. In the lung, MPO activity peaked at 12 and 96 hours, with BAL cytokine concentrations peaking at 12 hours, followed by lung edema at 24 hours, and BAL cell count at 48 hours. Importantly, no significant changes in BAL protein concentration or arterial blood gas-pH levels were evident over the same period, and only modest changes were observed in respiratory mechanics. Caerulein-induced AP results in minor lung injury, which is not sufficient to allow protein permeability and substantially alter respiratory mechanics.

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“…In an acute pancreatitis model induced by pancreaticobiliary duct obstruction with cerulein stimulation and systemic hypotension in the rat, Tetsuya Hirano and Tadao Manabe further confirmed that preoperatively administered urinastatin was more protective than that used postoperatively [31]. More recently, in a study conducted by Yun Ju Jo et al, a human leukocyte elastase inhibitor, recombinant guamerin, significantly reduced the severity of cerulein-induced pancreatitis in rats when administered 30 min before the induction of pancreatitis [32]. In other studies, N-acetylcysteine (a strong antioxidant) and the cathepsin B inhibitor CA-074me administered preoperatively demonstrated beneficial effects in experimentally induced acute pancreatitis [33], [34].…”

Section: Discussionmentioning

confidence: 86%

Beneficial Effects of Trypsin Inhibitors Derived from a Spider Venom Peptide in L-Arginine-Induced Severe Acute Pancreatitis in Mice

et al. 2013

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HWTI is a 55-residue protein isolated from the venom of the spider Ornithoctonus huwena. It is a potent trypsin inhibitor and a moderate voltage-gated potassium channel blocker. Here, we designed and expressed two HWTI mutants, HWTI-mut1 and HWTI-mut2, in which the potassium channel inhibitory activity was reduced while the trypsin inhibitory activity of the wild type form (approximately 5 EPU/mg) was retained. Animal studies showed that these mutants were less toxic than HWTI. The effects of HWTI and HWTI-mut1 were examined in a mouse model of acute pancreatitis induced by intraperitoneal injection of a large dose of L-arginine (4 mg/kg, twice). Serum amylase and serum lipase activities were assessed, and pathological sections of the pancreas were examined. Treatment with HWTI and HWTI-mut1 significantly reduced serum amylase and lipase levels in a dose dependent manner. Compared with the control group, at 4 mg/kg, HWTI significantly reduced serum amylase level by 47% and serum lipase level by 73%, while HWTI-mut1 significantly reduced serum amylase level by 59% and serum lipase level by 72%. Moreover, HWTI and HWTI-mut1 effectively protected the pancreas from acinar cell damage and inflammatory cell infiltration. The trypsin inhibitory potency and lower neurotoxicity of HWTI-mut1 suggest that it could potentially be developed as a drug for the treatment of acute pancreatitis with few side effects.

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The effects of a new human leukocyte elastase inhibitor (recombinant guamerin) on cerulein-induced pancreatitis in rats

Cited by 9 publications

References 33 publications

Ulinastatin activates the renin–angiotensin system to ameliorate the pathophysiology of severe acute pancreatitis

Ulinastatin activates the renin–angiotensin system to ameliorate the pathophysiology of severe acute pancreatitis

Caerulein-induced acute pancreatitis results in mild lung inflammation and altered respiratory mechanics

Beneficial Effects of Trypsin Inhibitors Derived from a Spider Venom Peptide in L-Arginine-Induced Severe Acute Pancreatitis in Mice

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