Abstract
Critically ill patients with sepsis require a multidisciplinary approach, as this situation implies multiorgan distress, with most of the bodily biochemical and cellular systems being affected by the condition. Moreover, sepsis is characterized by a multitude of biochemical interactions and by dynamic changes of the immune system. At the moment, there is a gap in our understanding of the cellular, genetic, and molecular mechanisms involved in sepsis. One of the systems intensely studied in recent years is the endocannabinoid signaling pathway, as light was shed over a series of important interactions of cannabinoid receptors with biochemical pathways, specifically for sepsis. Furthermore, a series of important implications on inflammation and the immune system that are induced by the activity of cannabinoid receptors stimulated by the delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) have been noticed. One of the most important is their ability to reduce the biosynthesis of pro-inflammatory mediators and the modulation of immune mechanisms. Different studies have reported that cannabinoids can reduce oxidative stress at mitochondrial and cellular levels. The aim of this review paper was to present, in detail, the important mechanisms modulated by the endocannabinoid signaling pathway, as well as of the molecular and cellular links it has with sepsis. At the same time, we wish to present the possible implications of cannabinoids in the most important biological pathways involved in sepsis, such as inflammation, redox activity, immune system, and epigenetic expression.
Highlights
Sepsis is one of the main causes of death in the intensive care unit (ICU) worldwide
If we look at the overall context of sepsis, macrophages and neutrophils are the main substrates responsible for increased free radicals (FR), reactive oxygen species (ROS), and reactive nitrogen species (RNS), affecting important processes such as cellular metabolism, angiogenesis, and the mitochondrial respiratory chain [96]
One of the major objectives of this review was to merge the results presented by other studies on the impact of cannabinoids on the main mechanisms involved in sepsis, such as inflammation, redox activity, and the immune expression
Summary
Sepsis is one of the main causes of death in the intensive care unit (ICU) worldwide. The main mechanisms involved in the pathogenic cascade and in the evolution of sepsis are represented by the inflammatory response, immune response, and redox activity, followed by the involvement of cellular defects, which all lead to severe organ dysfunction. Adding to this phenomenon are severe respiratory infections; tissue hypoxia; acute kidney injury (AKI); metabolic imbalances; and, last but not least, derangements of the biological system as a whole. We wish to present and put into context the implications of endogenous and exogenous cannabinoids on the inflammatory and redox profiles, and on the immune response, in order to present as complete of an image as is possible of their involvement in sepsis
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