Abstract
Aim:
To determine whether carbon monoxide (CO)-releasing molecules-liberated CO suppress inflammatory cytokine production and oxidative stress in the small intestine of burnt mice.
Methods:
Twenty-eight mice were assigned to 4 groups. The mice in the sham group (n=7) underwent sham thermal injury, whereas the mice in the burn group (n=7) received 15% total body surface area full-thickness thermal injury, the mice in the burn+CO-releasing molecules (CORM)-2 group (n=7) underwent the same injury with immediate administration of CORM-2 (8 mg/kg, iv), and the mice in the burn+inactivated CORM (iCORM)-2 group (n=7) underwent the same injury with immediate administration of iCORM-2. The levels of inflammatory cytokines in the tissue homogenates were measured by ELISA. The levels of malondialdehyde (MDA), nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) in the small intestine were also assessed. In the in vitro experiment, Caco-2 cells were stimulated by experimental mouse sera (50%, v/v) for 4 h. Subsequently, the levels of interleukin (IL)-8 and NO in the supernatants were assessed. Reactive oxygen species (ROS) generation in Caco-2 cells was also measured.
Results:
The treatment of burnt mice with CORM-2 significantly attenuated the levels of IL-1β, TNF-α, MDA, and NO in tissue homogenates. This was accompanied by a decrease of iNOS expression. In parallel, the levels of IL-8, NO, and intracellular ROS generation in the supernatants of Caco-2 stimulated by the CORM-2-treated burnt mouse sera was markedly decreased.
Conclusion:
CORM-released CO attenuates the production of inflammatory cytokines, prevents burn-induced ROS generation, and suppresses the oxidative stress in the small intestine of burnt mice by interfering with the protein expression of iNOS.
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Project supported by the National Natural Science Foundation of China (No 30772256).
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Liu, Dm., Sun, Bw., Sun, Zw. et al. Suppression of inflammatory cytokine production and oxidative stress by CO-releasing molecules—liberated CO in the small intestine of thermally-injured mice. Acta Pharmacol Sin 29, 838–846 (2008). https://doi.org/10.1111/j.1745-7254.2008.00816.x
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DOI: https://doi.org/10.1111/j.1745-7254.2008.00816.x
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