CARBON MONOXIDE SUPPRESSES PRODUCTION OF PRO-INFLAMMATORY CYTOKINES DURING ISCHEMIA-REPERFUSION
10.32999/ksu2524-0838/2022-33-4
Abstract
The endogenously produced gaseous transmitter carbon monoxide (CO) affects the cardiovascular system. Enzymes responsible for CO synthesis have been found in endothelial cells and smooth muscle. The mechanism of physiological action of CO is similar to that of nitric oxide. CO is formed from heme, which is part of the heme-containing proteins under the influence of heme oxygenase enzymes. Inducible heme oxygenase has a very important role in the adaptation of body cells and tissues to stress conditions. Ischemic-reperfusion injury accompanies cardiovascular diseases. When exposed to ischemia, mast cell macrophages are activated. After that, the production of pro-inflammatory cytokines increases. Elevated levels of these cytokines attract leukocytes and initiate inflammation in ischemic-damaged tissue. Myocardial ischemia-reperfusion was modelled in vivo in Wistar rats, and a polypropylene ligature was applied to the left coronary artery. Two groups were formed: experimental and control. In animals from both groups, a 30-minute ischemia followed by a 90-minute reperfusion was performed. Animals in the experimental group, before surgery, received CO inhalation at a dose of 250 ppm for 1 hour before ischemia-reperfusion of the heart. Blood samples were collected from each animal. In blood serum obtained 3, 6, 12, and 24 hours after reperfusion, we measured the mRNA for cyclooxygenase (COX)-2, inducible nitric oxide synthase, and the levels of cytokines IL-1β, IFN-α, IL-6, and TNF-α. Analysis of the obtained results showed that CO inhalation at a low dose and short exposure reduces the production of pro-inflammatory cytokines after ischemia-reperfusion. The level of IL-6 and IL-1β was reduced up to 3 hours after ischemia in the group of animals that received low concentrations of CO. mRNA expression for iNOS and COX-2 was also reduced in animals given a low dose of CO for up to 3 hours. TNF-α levels in blood serum decrease after exposure to inhaled CO for up to 6 hours after exposure to ischemia. 12 hours after reperfusion, mRNA expression for iNOS increased significantly. IL-1β after 5 hours recorded an increase in this cytokine.
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