Hydrogen sulfide is a novel mediator of lipopolysaccharide-induced inflammation in the mouse Export

@article{citeulike:3832114, abstract = {Hydrogen sulfide (H2S) is synthesized in the body from L-cysteine by several enzymes including cystathionine--lyase (CSE). To date, there is little information about the potential role of H2S in inflammation. We have now investigated the part played by H2S in endotoxin-induced inflammation in the mouse. E. coli lipopolysaccharide (LPS) administration produced a dose (10 and 20 mg/kg ip)- and time (6 and 24 h)-dependent increase in plasma H2S concentration. LPS (10 mg/kg ip, 6 h) increased plasma H2S concentration from 34.1 {+/-} 0.7 M to 40.9 {+/-} 0.6 M (n=6, P<0.05) while H2S formation from added L-cysteine was increased in both liver and kidney. CSE gene expression was also increased in both liver (94.2{+/-}2.7\%, n=6, P<0.05) and kidney (77.5{+/-}3.2\%, n=6, P<0.05). LPS injection also elevated lung (148.2{+/-}2.6\%, n=6, P<0.05) and kidney (78.8{+/-}8.2\%, n=6, P<0.05) myeloperoxidase (MPO, a marker of tissue neutrophil infiltration) activity alongside histological evidence of lung, liver, and kidney tissue inflammatory damage. Plasma nitrate/nitrite (NOx) concentration was additionally elevated in a time- and dose-dependent manner in LPS-injected animals. To examine directly the possible proinflammatory effect of H2S, mice were administered sodium hydrosulfide (H2S donor drug, 14 mol/kg ip) that resulted in marked histological signs of lung inflammation, increased lung and liver MPO activity, and raised plasma TNF- concentration (4.6{+/-}1.4 ng/ml, n=6). In contrast, DL-propargylglycine (CSE inhibitor, 50 mg/kg ip), exhibited marked anti-inflammatory activity as evidenced by reduced lung and liver MPO activity, and ameliorated lung and liver tissue damage. In separate experiments, we also detected significantly higher (150.5{+/-}43.7 M c.f. 43.8{+/-}5.1 M, n=5, P<0.05) plasma H2S levels in humans with septic shock. These findings suggest that H2S exhibits proinflammatory activity in endotoxic shock and suggest a new approach to the development of novel drugs for this condition. Key words: cystathionine--lyase H2S 10.1096/fj.04-3583fje}, author = {Li, Ling and Bhatia, Madhav and Zhu, Yi Z. and Zhu, Yi C. and Ramnath, Raina D. and Wang, Zhong J. and Anuar, Farhana B. and Whiteman, Matthew and Salto-Tellez, Manuel and Moore, Philip K.}, citeulike-article-id = {3832114}, citeulike-linkout-0 = {http://dx.doi.org/10.1096/fj.04-3583fje}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15863703}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15863703}, day = {29}, doi = {10.1096/fj.04-3583fje}, journal = {FASEB J.}, keywords = {endotoxemia, h2s, lps}, month = {April}, pages = {04-3583fje+}, posted-at = {2008-12-28 23:25:38}, priority = {2}, title = {Hydrogen sulfide is a novel mediator of lipopolysaccharide-induced inflammation in the mouse}, url = {http://dx.doi.org/10.1096/fj.04-3583fje}, year = {2005} }

TY - JOUR ID - citeulike:3832114 L3 - citeulike-article-id:3832114 N2 - Hydrogen sulfide (H2S) is synthesized in the body from L-cysteine by several enzymes including cystathionine--lyase (CSE). To date, there is little information about the potential role of H2S in inflammation. We have now investigated the part played by H2S in endotoxin-induced inflammation in the mouse. E. coli lipopolysaccharide (LPS) administration produced a dose (10 and 20 mg/kg ip)- and time (6 and 24 h)-dependent increase in plasma H2S concentration. LPS (10 mg/kg ip, 6 h) increased plasma H2S concentration from 34.1 {+/-} 0.7 M to 40.9 {+/-} 0.6 M (n=6, P<0.05) while H2S formation from added L-cysteine was increased in both liver and kidney. CSE gene expression was also increased in both liver (94.2{+/-}2.7%, n=6, P<0.05) and kidney (77.5{+/-}3.2%, n=6, P<0.05). LPS injection also elevated lung (148.2{+/-}2.6%, n=6, P<0.05) and kidney (78.8{+/-}8.2%, n=6, P<0.05) myeloperoxidase (MPO, a marker of tissue neutrophil infiltration) activity alongside histological evidence of lung, liver, and kidney tissue inflammatory damage. Plasma nitrate/nitrite (NOx) concentration was additionally elevated in a time- and dose-dependent manner in LPS-injected animals. To examine directly the possible proinflammatory effect of H2S, mice were administered sodium hydrosulfide (H2S donor drug, 14 mol/kg ip) that resulted in marked histological signs of lung inflammation, increased lung and liver MPO activity, and raised plasma TNF- concentration (4.6{+/-}1.4 ng/ml, n=6). In contrast, DL-propargylglycine (CSE inhibitor, 50 mg/kg ip), exhibited marked anti-inflammatory activity as evidenced by reduced lung and liver MPO activity, and ameliorated lung and liver tissue damage. In separate experiments, we also detected significantly higher (150.5{+/-}43.7 M c.f. 43.8{+/-}5.1 M, n=5, P<0.05) plasma H2S levels in humans with septic shock. These findings suggest that H2S exhibits proinflammatory activity in endotoxic shock and suggest a new approach to the development of novel drugs for this condition. Key words: cystathionine--lyase H2S 10.1096/fj.04-3583fje JF - FASEB J. TI - Hydrogen sulfide is a novel mediator of lipopolysaccharide-induced inflammation in the mouse SP - 04-3583fje KW - endotoxemia KW - h2s KW - lps AU - Li, Ling AU - Bhatia, Madhav AU - Zhu, Yi AU - Zhu, Yi AU - Ramnath, Raina AU - Wang, Zhong AU - Anuar, Farhana AU - Whiteman, Matthew AU - Salto-Tellez, Manuel AU - Moore, Philip PY - 2005/04/29/ UR - http://dx.doi.org/10.1096/fj.04-3583fje ER -