Potential effects of PKC or protease inhibitors on acute pancreatitis-induced tissue injury in rats

Shi, Changbin; Zhao, Xia; Wang, Xiangdong; Zhao, Li‐Ming; Andersson, Roland

doi:10.1016/j.vph.2007.01.009

Cited by 13 publications

(6 citation statements)

References 40 publications

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“…Other studies using AEBSF to block serine proteases at concentrations over 1 mM did observe cell death or toxicity in primary bone and osteoblastic cell (Gorski et al 2009) as well as in RAW264.7 cell cultures (Wijayanti et al 2005). Furthermore, studies with in vivo inhibition of serine proteases with AEBSF in mice have reported no overt toxicity (Buitrago-Rey et al 2002;Shi et al 2007;Megyeri et al 1999). However, an increase in cell death may occur in AEBSF-exposed cells with longer culture periods, or at a higher dose, or in cells at different developmental/activation stages.…”

Section: Discussionmentioning

confidence: 98%

Serine protease inhibitor, 4-(2-aminoethyl)-benzene sulfonyl fluoride, impairs IL-12-induced activation of pSTAT4β, NFκB, and select pro-inflammatory mediators from estrogen-treated mice

2011

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Section: Discussionmentioning

confidence: 98%

Serine protease inhibitor, 4-(2-aminoethyl)-benzene sulfonyl fluoride, impairs IL-12-induced activation of pSTAT4β, NFκB, and select pro-inflammatory mediators from estrogen-treated mice

2011

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“…Inhibition of the neutrophil infiltration can attenuate the pancreatic injury. 23 Treatment with alpha-pinene significantly decreased the pancreatic MPO levels probably due to its anti-inflammatory action. One of the lipid peroxidation marker, which is elevated in L-arginine treated rats.…”

Section: Assessment Of Interleukins and C-reactive Proteinmentioning

confidence: 94%

Current Scenario of Patent Act: Compulsory Licensing

Chander¹,

Choudhary²,

Kumar³

2013

IJPER

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Objective: Screening of alpha-pinene on L-arginine induced acute pancreatitis model. Material and Methods: In this model the acute pancreatitis was determined at 24h by determination of pancreatic wet weight/body weight ratio, nitrate/nitrite levels, lipid peroxidation (thiobarbituric acid reactive substances (TBARS)], proinflammatory cytokines [tumor necrosis factor (TNF)-α, C-reactive proteins (CRP) and interleukin (IL)], pancreatic myeloperoxidase (MPO) activity and serum levels of amylase and lipase. Results: Administration of L-arginine had induced pancreatitis and this was characterized by pulmonary complication including altered pancreatic wet weight/body weight ratio, nitrate/nitrite levels, proinflammatory cytokines, TBARS, MPO and serum levels of amylase and lipase. Treatment with alpha-pinene (100 and 200mg/kg) dose significantly attenuated the L-arginine-induced pancreatitis and related complication. Conclusion: The histological findings proved the amelioration of pancreatic injury by alphapinene and biochemical parameters proved anti-inflammatory and antioxidant property of alpha-pinene.

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“…Much of the data in the literature on the mechanisms of PKC isoform involvement in ARDS pathogenesis is inferred indirectly from studies in which pharmacological modulation of PKC activity (62–64), or the use of knockout mice for specific PKC isoforms (65, 66), is correlated with improvements in commonly employed experimental animal models of lung injury.…”

Section: Pkcs and Pathogenesis Of Ardsmentioning

confidence: 99%

“…The PKC inhibitor polymixin B (broad spectrum inhibitor which also binds endotoxin) attenuated lung injury and lowered levels of TNF-α, IL-1β, MCP-1 and IL-10 in a murine model of lung injury secondary to acute pancreatitis, suggesting that broad spectrum PKC inhibition dampened the overall inflammatory response in the lung (64). Similarly, systemic infusion of staurosporine (broad spectrum inhibitor which also inhibits PKA and PKG) and polymixin B both reduced pancreatic and pulmonary MPO levels in a rat model of acute pancreatitis (62). …”

Section: Pkcs and Pathogenesis Of Ardsmentioning

confidence: 99%

Protein Kinase C and Acute Respiratory Distress Syndrome

Mondrinos

Kennedy²,

Lyons

et al. 2013

Shock

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The Acute Respiratory Distress Syndrome (ARDS) is a major public health problem and a leading source of morbidity in Intensive Care Units (ICUs). Lung tissue in patients with ARDS is characterized by inflammation, with exuberant neutrophil infiltration, activation and degranulation that is thought to initiate tissue injury through the release of proteases and oxygen radicals. Treatment of ARDS is supportive primarily because the underlying pathophysiology is poorly understood. This gap in knowledge must be addressed in order to identify urgently needed therapies. Recent research efforts in anti-inflammatory drug development have focused on identifying common control points in multiple signaling pathways. The protein kinase C (PKC) serine-threonine kinases are master regulators of proinflammatory signaling hubs, making them attractive therapeutic targets. Pharmacological inhibition of broad spectrum PKC activity and, more importantly, of specific PKC isoforms (as well as deletion of PKCs in mice) exerts protective effects in various experimental models of lung injury. Furthermore, PKC isoforms have been implicated in inflammatory processes that may be involved in the pathophysiologic changes that result in ARDS, including activation of innate immune and endothelial cells, neutrophil trafficking to the lung, regulation of alveolar epithelial barrier functions and control of neutrophil pro-inflammatory and pro-survival signaling. This review focuses on the mechanistic involvement of PKC isoforms in the pathogenesis of ARDS and highlights the potential of developing new therapeutic paradigms based on the selective inhibition (or activation) of specific PKC isoforms.

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Potential effects of PKC or protease inhibitors on acute pancreatitis-induced tissue injury in rats

Abstract: Background: Acute pancreatitis (AP) is still one of the severe diseases that cause the

Cited by 13 publications

References 40 publications

Serine protease inhibitor, 4-(2-aminoethyl)-benzene sulfonyl fluoride, impairs IL-12-induced activation of pSTAT4β, NFκB, and select pro-inflammatory mediators from estrogen-treated mice

Serine protease inhibitor, 4-(2-aminoethyl)-benzene sulfonyl fluoride, impairs IL-12-induced activation of pSTAT4β, NFκB, and select pro-inflammatory mediators from estrogen-treated mice

Current Scenario of Patent Act: Compulsory Licensing

Protein Kinase C and Acute Respiratory Distress Syndrome

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