Regulatory effect and mechanisms of carbon monoxide-releasing molecule II on hepatic energy metabolism in septic mice.
OBJECTIVE
To investigate the possible mechanisms of exogenous carbon monoxide-releasing molecule II (CORM-2) intervention on hepatic energy metabolism in experimental sepsis.


METHODS
Forty-eight C57BL/6 mice were randomly divided into four groups (n = 12): sham group; cecal ligation and puncture (CLP) group; CLP + CORM-2 group and CLP + iCORM-2 (inactive CORM-2) group. Survival rates were determined after 72 h. Twenty-four similarly treated mice (n = 6 in each group) were assayed for post-operative continuous blood glucose in the first 36 h. Thirty-six similarly treated mice (n = 9 in each group) underwent micro-positron emission tomography (PET) scanning after tail vein injection of (18)F-fluorodeoxyglucose (FDG) 24 h after operation. Plasma and liver specimens were collected for assay of liver pathology, alanine transaminase (ALT) and aspartate transaminase (AST) activities. Hepatic glucokinase activity, lactic acid levels and mitochondrial swelling were also determined.


RESULTS
Improved survival was observed in CORM-2 treated mice. Both the CLP and CLP + CORM-2 groups had sustained low blood glucose levels within the first post-operative 36 h. (18)F-FDG micro-PET images showed abnormally high levels of hepatic glucose metabolism (standardized uptake value) in the CLP group (2.76 ± 0.39 vs 0.84 ± 0.14, P < 0.01), which declined to normal levels after CORM-2 intervention (1.29 ± 0.32 vs 2.76 ± 0.39, P < 0.05). glucokinase activity was markedly increased in the CLP group (6.38 ± 0.56 U/g vs 4.60 ± 0.21 U/g, P < 0.01), but was normal after CORM-2 intervention (4.74 ± 0.14 U/g vs 6.38 ± 0.56 U/g, P < 0.05). CORM-2 suppressed plasma lactic acid levels (4.02 ± 0.02 mmol/L vs 7.72 ± 2.37 mmol/L, P < 0.05) and protected hepatic mitochondria in CLP mice. CORM-2 intervention also reduced elevated plasma AST (199.67 ± 11.08 U/L vs 379.67 ± 16.34 U/L, P < 0.05) and ALT (63.67 ± 12.23 U/L vs 112.67 ± 9.74 U/L, P < 0.05) activities in CLP mice.


CONCLUSIONS
The release of CO molecules by CORM-2 protects mitochondria and maintains a stable level of hepatic glucose metabolism. Thus, CORM-2 improves liver function and survival in septic mice.
Feng Liang, Jie Cao, Wei-Ting Qin, Xu Wang, Xue-Feng Qiu, Bing-Wei Sun, Department of Burn and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
Feng
F
Liang
Feng Liang, Jie Cao, Wei-Ting Qin, Xu Wang, Xue-Feng Qiu, Bing-Wei Sun, Department of Burn and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
Jie
J
Cao
Feng Liang, Jie Cao, Wei-Ting Qin, Xu Wang, Xue-Feng Qiu, Bing-Wei Sun, Department of Burn and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
Wei-Ting
WT
Qin
Feng Liang, Jie Cao, Wei-Ting Qin, Xu Wang, Xue-Feng Qiu, Bing-Wei Sun, Department of Burn and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
Xu
X
Wang
Feng Liang, Jie Cao, Wei-Ting Qin, Xu Wang, Xue-Feng Qiu, Bing-Wei Sun, Department of Burn and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
Xue-Feng
XF
Qiu
Feng Liang, Jie Cao, Wei-Ting Qin, Xu Wang, Xue-Feng Qiu, Bing-Wei Sun, Department of Burn and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
Bing-Wei
BW
Sun
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D002248:Carbon Monoxide / Q000737:chemistry; D002432:Cecum / Q000601:surgery; D019788:Fluorodeoxyglucose F18 / Q000737:chemistry; D005786:Gene Expression Regulation; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D009942:Organometallic Compounds / Q000737:chemistry*; D049268:Positron-Emission Tomography; D018805:Sepsis / Q000378:metabolism*
D001786:Blood Glucose; D009942:Organometallic Compounds; C447082:tricarbonyldichlororuthenium (II) dimer; D019788:Fluorodeoxyglucose F18; D002248:Carbon Monoxide; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
Carbon monoxide; Energy metabolism; Liver; Regulation; Sepsis