Inhibition of Hydrogen Sulfide Synthesis Attenuates Chemokine Production and Protects Mice Against Acute Pancreatitis and Associated Lung Injury

Pancreas ◽  
2008 ◽  
Vol 36 (4) ◽  
pp. e24-e31 ◽  
Author(s):  
Ramasamy Tamizhselvi ◽  
Philip K. Moore ◽  
Madhav Bhatia
Keyword(s):  
Acute Pancreatitis ◽  
Hydrogen Sulfide ◽  
Lung Injury ◽  
Chemokine Production

Role of hydrogen sulfide in acute pancreatitis and associated lung injury

2005 ◽  
Vol 19 (6) ◽  
pp. 1-17 ◽  
Author(s):  
Madhav Bhatia ◽  
Fei Ling Wong ◽  
Di Fu ◽  
Hon Yen Lau ◽  
Shabbir M. Moochhala ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Hydrogen Sulfide ◽  
Lung Injury

scholarly journals H2S in acute lung injury: a therapeutic dead end(?)

2020 ◽  
Vol 8 (S1) ◽  
Author(s):  
Tamara Merz ◽  
Nicole Denoix ◽  
Martin Wepler ◽  
Holger Gäßler ◽  
David A. C. Messerer ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Circulatory Shock ◽  
Therapeutic Window ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Clinical Reality ◽  
Dead End

AbstractThis review addresses the plausibility of hydrogen sulfide (H2S) therapy for acute lung injury (ALI) and circulatory shock, by contrasting the promising preclinical results to the present clinical reality. The review discusses how the narrow therapeutic window and width, and potentially toxic effects, the route, dosing, and timing of administration all have to be balanced out very carefully. The development of standardized methods to determine in vitro and in vivo H2S concentrations, and the pharmacokinetics and pharmacodynamics of H2S-releasing compounds is a necessity to facilitate the safety of H2S-based therapies. We suggest the potential of exploiting already clinically approved compounds, which are known or unknown H2S donors, as a surrogate strategy.

Hydrogen sulfide attenuates ferroptosis and stimulates autophagy by blocking mTOR signaling in sepsis-induced acute lung injury

2022 ◽  
Vol 141 ◽  
pp. 318-327
Author(s):  
Jianhua Li ◽  
Mengyu Li ◽  
Ling Li ◽  
Jiamin Ma ◽  
Chengye Yao ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Mtor Signaling

Complement factor C5a exerts an anti-inflammatory effect in acute pancreatitis and associated lung injury

2001 ◽  
Vol 280 (5) ◽  
pp. G974-G978 ◽  
Author(s):  
Madhav Bhatia ◽  
Ashok K. Saluja ◽  
Vijay P. Singh ◽  
Jean-Louis Frossard ◽  
Hong-Sik Lee ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Lung Injury ◽  
Acute Inflammation ◽  
Complement Factor ◽  
Neutrophil Sequestration ◽  
C5a Receptors ◽  
Acinar Cell Necrosis ◽  
Anti Inflammatory ◽  
Type Strains ◽  
Inflammatory Effect

Complement factor C5a acting via C5a receptors (C5aR) is recognized as an anaphylotoxin and chemoattractant that exerts proinflammatory effects in many pathological states. The effects of C5a and C5aR in acute pancreatitis and in pancreatitis-associated lung injury were evaluated using genetically altered mice that either lack C5aR or do not express C5. Pancreatitis was induced by administration of 12 hourly injections of cerulein (50 μg/kg ip). The severity of pancreatitis was determined by measuring serum amylase, neutrophil sequestration in the pancreas, and acinar cell necrosis. The severity of lung injury was evaluated by measuring neutrophil sequestration in the lung and pulmonary microvascular permeability. In both strains of genetically altered mice, the severity of pancreatitis and pancreatitis-associated lung injury was greater than that noted in the comparison wild-type strains of C5aR- and C5-sufficient animals. This exacerbation of injury in the absence of C5a function indicates that, in pancreatitis, C5a exerts an anti-inflammatory effect. Potentially, C5a and its receptor are capable of both promoting and reducing the extent of acute inflammation.

Geranylgeranyl transferase regulates CXC chemokine formation in alveolar macrophages and neutrophil recruitment in septic lung injury

2013 ◽  
Vol 304 (4) ◽  
pp. L221-L229 ◽  
Author(s):  
Zirak Hasan ◽  
Milladur Rahman ◽  
Karzan Palani ◽  
Ingvar Syk ◽  
Bengt Jeppsson ◽  
...  
Keyword(s):  
Lung Injury ◽  
Alveolar Macrophages ◽  
Neutrophil Infiltration ◽  
Abdominal Sepsis ◽  
Neutrophil Recruitment ◽  
Chemokine Production ◽  
Tnf Α ◽  
Cxc Chemokine ◽  
Geranylgeranyl Transferase

Overwhelming accumulation of neutrophils is a significant component in septic lung damage, although the signaling mechanisms behind neutrophil infiltration in the lung remain elusive. In the present study, we hypothesized that geranylgeranylation might regulate the inflammatory response in abdominal sepsis. Male C57BL/6 mice received the geranylgeranyl transferase inhibitor, GGTI-2133, before cecal ligation and puncture (CLP). Bronchoalveolar lavage fluid and lung tissue were harvested for analysis of neutrophil infiltration, as well as edema and CXC chemokine formation. Blood was collected for analysis of Mac-1 on neutrophils and CD40L on platelets. Gene expression of CXC chemokines, tumor necrosis factor-α (TNF-α), and CCL2 chemokine was determined by quantitative RT-PCR in isolated alveolar macrophages. Administration of GGTI-2133 markedly decreased CLP-induced infiltration of neutrophils, edema, and tissue injury in the lung. CLP triggered clear-cut upregulation of Mac-1 on neutrophils. Inhibition of geranylgeranyl transferase reduced CLP-evoked upregulation of Mac-1 on neutrophils in vivo but had no effect on chemokine-induced expression of Mac-1 on isolated neutrophils in vitro. Notably, GGTI-2133 abolished CLP-induced formation of CXC chemokines, TNF-α, and CCL2 in alveolar macrophages in the lung. Geranylgeranyl transferase inhibition had no effect on sepsis-induced platelet shedding of CD40L. In addition, inhibition of geranylgeranyl transferase markedly decreased CXC chemokine-triggered neutrophil chemotaxis in vitro. Taken together, our findings suggest that geranylgeranyl transferase is an important regulator of CXC chemokine production and neutrophil recruitment in the lung. We conclude that inhibition of geranylgeranyl transferase might be a potent way to attenuate acute lung injury in abdominal sepsis.

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