Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Reviews: Regulatory Mechanism of Damage-Associated Molecular Patterns and Application to Drug Discovery
A new approach to combat the sepsis including COVID-19 by accelerating detoxification of hemolysis-related DAMPs
Daiki OusakaMasahiro Nishibori
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JOURNAL FREE ACCESS

2022 Volume 157 Issue 6 Pages 422-425

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Abstract

Sepsis is one of the leading cause of death worldwide. Recently, several studies suggested that free-hemoglobin and heme derived from hemolysis are important factors which may be associated with severity of septic patients including COVID-19. In other words, hemolysis-derived products enhance the inflammatory responses as damage-associated molecular patterns (DAMPs) in both intravascular and extravascular space. In addition, hemoglobin has vasoconstrictive activity by depleting nitric oxide, whereas heme or Fe2+ produce reactive oxygen species (ROS) through Fenton reaction leading to tissue injury. At present, we have no therapeutic options against sepsis-related hemolysis in clinical settings, however, there might be two therapeutic strategies in this regard. One is supplemental therapy of depleted scavenging proteins such as haptoglobin and hemopexin, the other is activation of the internal scavenging system including macrophage-CD163 pathway. These novel targets against sepsis are also critical for the next pandemic. In this review, we summarize the current issues regarding sepsis-related hemolysis including COVID-19, as well as for future perspectives.

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© 2022 by The Japanese Pharmacological Society
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