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The effects of arginase inhibitor on lung oxidative stress and inflammation caused by pneumoperitoneum in rats

 Jin Sun Cho  ;  Young Jun Oh  ;  Ok Soo Kim  ;  Sungwon Na 
 BMC ANESTHESIOLOGY, Vol.15 : 129, 2015 
Journal Title
Issue Date
Aminocaproates/administration & dosage ; Aminocaproates/pharmacology* ; Animals ; Arginase/antagonists & inhibitors* ; Boron Compounds/administration & dosage ; Boron Compounds/pharmacology* ; Cytokines/metabolism ; Disease Models, Animal ; Enzyme Inhibitors/administration & dosage ; Enzyme Inhibitors/pharmacology ; Inflammation/etiology ; Inflammation/prevention & control* ; Injections, Subcutaneous ; Lung Injury/etiology ; Lung Injury/prevention & control ; Male ; Malondialdehyde/metabolism ; Nitric Oxide/metabolism ; Oxidative Stress/drug effects* ; Pneumoperitoneum/complications* ; Pneumoperitoneum/drug therapy ; Rats ; Rats, Sprague-Dawley
Arginase ; Inflammation ; Lung injury ; Nitric oxide ; Oxidative stress ; Pneumoperitoneum
BACKGROUND: Pneumoperitoneum-induced oxidative stress and organ injury are known to be associated with nitric oxide (NO) inactivation. Because arginase competes with NO synthase (NOS) for a common substrate, L-arginine, arginase inhibition may increase NO bioavailability. Therefore, we evaluated the ability of the arginase inhibitor, 2 (S)-amino-6-boronohexanoic acid (ABH), to attenuate pneumoperitoneum-induced decrease of NO bioavailability and lung injury. METHODS: Thirty rats were randomly divided into the following groups: 1) the PP-ABH group received a subcutaneous injection of ABH (5 mg/kg) 1 h before induction of pneumoperitoneum (insufflation to intraperitoneal pressure of 15 mmHg for 60 min); 2) the PP group received saline by subcutaneous injection 1 h before induction of pneumoperitoneum; and 3) the control group received saline by subcutaneous injection before a sham procedure with no gas insufflation. After desufflation, blood was collected to determine levels of plasma nitrite, NOS, inflammatory cytokines, and malondialdehyde, a marker of oxidative stress. Lung tissue was obtained for histological evaluation. RESULTS: We found that plasma nitrite levels were lower in the PP group and higher in the PP-ABH group, compared with controls (P <0.01 and P <0.05, respectively). In the PP group, endothelial NOS activity was decreased and inducible NOS activity was increased compared with the PP-ABH and control groups. Malondialdehyde levels increased 3-fold in the PP group and 2-fold in the PP-ABH group compared with controls. Tumor necrosis factor-α, interleukin-6, and interleukin-1ß levels were elevated in the PP group compared to the control group, but the increase in cytokine production was attenuated or blocked in the PP-ABH group. Lung injury scores were 4.8-fold higher in the PP group and 2-fold higher in the PP-ABH group compared with controls (P <0.001 and P <0.01, respectively). DISCUSSION: Pneumoperitoneum decreases NO bioavailability and increases the inflammation cytokines, resulting in organ injuries. Inhibition of arginase activity could maintain NO bioavailability by attenuating pneumoperitoneum-induced changes in NOS activity. In addition, arginase inhibition attenuated the oxidative stress and inflammation and decreased the severity of lung injury caused by pneumoperitoneum. CONCLUSIONS: By increasing NO bioavailability and suppressing oxidative stress and inflammation, pretreatment with an arginase inhibitor may protect against lung injury caused by pneumoperitoneum.
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1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
Yonsei Authors
Na, Sungwon(나성원) ORCID logo https://orcid.org/0000-0002-1170-8042
Oh, Young Jun(오영준) ORCID logo https://orcid.org/0000-0002-6258-5695
Cho, Jin Sun(조진선) ORCID logo https://orcid.org/0000-0002-5408-4188
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