Resolution of Inflammation after Skeletal Muscle Ischemia–Reperfusion Injury: A Focus on the Lipid Mediators Lipoxins, Resolvins, Protectins and Maresins

Abstract

Skeletal muscle ischemia reperfusion is very frequent in humans and results not only in muscle destruction but also in multi-organ failure and death via systemic effects related to inflammation and oxidative stress. In addition to overabundance of pro-inflammatory stimuli, excessive and uncontrolled inflammation can also result from defects in resolution signaling. Importantly, the resolution of inflammation is an active process also based on specific lipid mediators including lipoxins, resolvins and maresins that orchestrate the potential return to tissue homeostasis. Thus, lipid mediators have received growing attention since they dampen deleterious effects related to ischemia–reperfusion. For instance, the treatment of skeletal muscles with resolvins prior to ischemia decreases polymorphonuclear leukocyte (PMN) infiltration. Additionally, remote alterations in lungs or kidneys are reduced when enhancing lipid mediators’ functions. Accordingly, lipoxins prevented oxidative-stress-mediated tissue injuries, macrophage polarization was modified and in mice lacking DRV2 receptors, ischemia/reperfusion resulted in excessive leukocyte accumulation. In this review, we first aimed to describe the inflammatory response during ischemia and reperfusion in skeletal muscle and then discuss recent discoveries in resolution pathways. We focused on the role of specialized pro-resolving mediators (SPMs) derived from polyunsaturated fatty acids (PUFAs) and their potential therapeutic applications.

Carbon Dot Nanozyme Ameliorating Ischemia-Reperfusion-Induced Muscle Injury by Antioxidation and Downregulating iNOS/COX-2 Pathway

“…This approach resulted in C-dots being accumulated at sites of IR injury. Due to the inflammation plays a significant role in IR, 36 we aimed to investigate the potential of C-dot nanozyme in reducing inflammation levels and tissue edema in skeletal muscle following limb IR injury. Muscle tissue injury was assessed using H&E staining as shown in Figure 4 b and S11 .…”

Lipid metabolism in B cell biology

“…Polyunsaturated fatty acids (PUFAs) with two or more double bonds such as arachidonic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) have two main roles: as precursors of signalling molecules and as building blocks of membrane lipids. PUFAs can also give rise to lipid mediators such as lipoxins, resolvins, protectins, and maresins which play a role in the resolution phase of inflammation [ 20 ] and have been reported to enhance B cell differentiation to plasma cells (PCs) [ 21 ]. Monounsaturated fatty acids (MUFAs) such as oleic acid (OA) and palmitoleic acid (PO) have been reported to support mitochondrial metabolism and mammalian Target of Rapamycin C1 (mTORC1) activity in B cells [ 22 ].…”

Evaluation of the effect of enriched hydrogen saline solution on distant organ (lung) damage in skeletal muscle ischemia reperfusion in rats

“…All these responses lead to the accumulation of inflammatory infiltrates in the alveoli and interstitium. 6 – 9 These factors are responsible for decreased gas exchange and increased work of breathing, exposing the lungs to acute respiratory distress syndrome (ARDS), 10 which may lead to mortality rates of up to 40%. 11 Thus, developing effective treatments for skeletal muscle IR injury is imperative to protect the lungs.…”

“…Skeletal muscle IR can release inflammatory cytokines, endogenous danger molecules, and oxygen-free radicals, and activate the complement system. [6][7][8][9] In normal physiological states, the venous circulation passing through the pulmonary vasculature acts as a neutrophil pool. In the lungs, there is an increased potential for neutrophil-endothelial interactions compared to other vascular beds.…”