Circulating levels of hydrogen sulfide and substance P in patients with sepsis

2017 ◽  
Vol 75 (4) ◽  
pp. 293-300 ◽  
Author(s):  
Ravinder Reddy Gaddam ◽  
Stephen Chambers ◽  
David Murdoch ◽  
Geoffrey Shaw ◽  
Madhav Bhatia
2021 ◽  
Vol 10 (19) ◽  
pp. 4460
Author(s):  
Rahib K. Islam ◽  
Erinn Donnelly ◽  
Kazi N. Islam

Human immunodeficiency virus (HIV) attacks the immune system and weakens the ability to fight infections/disease. Furthermore, HIV infection confers approximately two-fold higher risk of cardiac events compared with the general population. The pathological mechanisms responsible for the increased incidence of cardiovascular disease in HIV patients are largely unknown. We hypothesized that increased oxidative stress and attenuated circulating levels of the cardioprotective gaseous signaling molecules, nitric oxide (NO), and hydrogen sulfide (H2S) were involved in the cardiovascular pathobiology observed in HIV patients. Plasma samples from both HIV patients and age–matched normal subjects were used for all assays. Oxidative stress was determined by analyzing the levels of advanced oxidation protein products (AOPP) and H2O2. Antioxidant levels were determined by measuring the levels of trolox equivalent capacity. ADMA, hs-CRP, and IL-6 were determined by using ELISA. The levels of H2S (free H2S and sulfane sulfur) and NO2 (nitrite) were determined in the plasma samples by using gas chromatography and HPLC, respectively. In the present study we observed a marked induction in the levels of oxidative stress and decreased antioxidant status in the plasma of HIV patients as compared with the controls. Circulating levels of the cardiovascular disease biomarkers: ADMA, hs-CRP (high-sensitivity C-reactive protein), and IL-6 were significantly increased in the circulatory system of HIV patients. The levels of both nitrite and H2S/sulfane sulfur were significantly reduced in the plasma of HIV patients as compared with normal subjects. Our data demonstrate significant increases in circulating biomarkers of oxidative stress and cardiovascular (CV) in conjunction with decreased bioavailability of H2S and NO in HIV patients. Diminished levels of these two cardioprotective gaseous signaling molecules may be involved in the pathogenesis of CV disease in the setting of HIV.


2007 ◽  
Vol 179 (6) ◽  
pp. 4153-4160 ◽  
Author(s):  
Huili Zhang ◽  
Akhil Hegde ◽  
Siaw Wei Ng ◽  
Sharmila Adhikari ◽  
Shabbir M. Moochhala ◽  
...  

2009 ◽  
Vol 136 (5) ◽  
pp. A-543
Author(s):  
Eric WL Wee ◽  
Madhav Bhatia ◽  
Mark L. Fernandes ◽  
Krishnakumar Madhavan ◽  
Jennie Y. Wong ◽  
...  

Endocrinology ◽  
2011 ◽  
Vol 152 (6) ◽  
pp. 2197-2205 ◽  
Author(s):  
Iordanes Karagiannides ◽  
Dimitris Stavrakis ◽  
Kyriaki Bakirtzi ◽  
Efi Kokkotou ◽  
Tamara Pirtskhalava ◽  
...  

Peripheral administration of a specific neurokinin-1 receptor (NK-1R) antagonist to mice leads to reduced weight gain and circulating levels of insulin and leptin after high-fat diet (HFD). Here, we assessed the contribution of substance P (SP) and NK-1R in diet-induced obesity using NK-1R deficient [knockout (KO)] mice and extended our previous findings to show the effects of SP-NK-1R interactions on adipose tissue-associated insulin signaling and glucose metabolic responses. NK-1R KO and wild-type (WT) littermates were fed a HFD for 3 wk, and obesity-associated responses were determined. Compared with WT, NK-1 KO mice show reduced weight gain and circulating levels of leptin and insulin in response to HFD. Adiponectin receptor mRNA levels are higher in mesenteric fat and liver in NK-1 KO animals compared with WT, after HFD. Mesenteric fat from NK-1R KO mice fed with HFD has reduced stress-activated protein kinase/c-Jun N-terminal kinase and protein kinase Cθ activation compared with WT mice. After glucose challenge, NK-1R KO mice remove glucose from the circulation more efficiently than WT and pair-fed controls, suggesting an additional peripheral effect of NK-1R-mediated signaling on glucose metabolism. Glucose uptake experiments in isolated rat adipocytes showed that SP directly inhibits insulin-mediated glucose uptake. Our results further establish a role for SP-NK-1R interactions in adipose tissue responses, specifically as they relate to obesity-associated pathologies such as glucose intolerance and insulin resistance. Our results highlight this pathway as an important therapeutic approach for type 2 diabetes.


PLoS ONE ◽  
2011 ◽  
Vol 6 (9) ◽  
pp. e24535 ◽  
Author(s):  
Seah-Fang Ang ◽  
Shabbir M. Moochhala ◽  
Paul A. MacAry ◽  
Madhav Bhatia

2019 ◽  
Vol 20 (13) ◽  
pp. 3191 ◽  
Author(s):  
Ravinder Gaddam ◽  
Stephen Chambers ◽  
Robin Fraser ◽  
Victoria Cogger ◽  
David Le Couteur ◽  
...  

Cystathionine-γ-lyase (CSE) is a hydrogen sulfide (H2S)-synthesizing enzyme that promotes inflammation by upregulating H2S in sepsis. Liver sinusoidal endothelial cells (LSECs) are fenestrated endothelial cells (liver sieve) that undergo alteration during sepsis and H2S plays a role in this process. Substance P (SP) is encoded by the preprotachykinin A (PPTA) gene, and promotes inflammation in sepsis; however, its regulation by H2S is poorly understood. Furthermore, the interaction between H2S and SP in modulating LSEC fenestrations following sepsis remains unclear. This study aimed to investigate whether CSE/H2S regulates SP and the neurokinin-1 receptor (NK-1R) and modulates fenestrations in LSECs following caecal ligation and puncture (CLP)-induced sepsis. Here we report that the absence of either CSE or H2S protects against liver sieve defenestration and gaps formation in LSECs in sepsis by decreased SP-NK-1R signaling. Following sepsis, there is an increased expression of liver CSE and H2S synthesis, and plasma H2S levels, which were aligned with higher SP levels in the liver, lungs and plasma and NK-1R in the liver and lungs. The genetic deletion of CSE led to decreased sepsis-induced SP and NK-1R in the liver, lungs and plasma SP suggesting H2S synthesized through CSE regulates the SP-NK-1R pathway in sepsis. Further, mice deficient in the SP-encoding gene (PPTA) preserved sepsis-induced LSEC defenestration and gaps formation, as seen by maintenance of patent fenestrations and fewer gaps. In conclusion, CSE/H2S regulates SP-NK-1R and modulates LSEC fenestrations in sepsis.


2010 ◽  
Vol 12 (10) ◽  
pp. 1191-1202 ◽  
Author(s):  
Madhav Bhatia
Keyword(s):  

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