The Interplay of Oxidative Stress and ROS Scavenging: Antioxidants as a Therapeutic Potential in Sepsis

Abstract

Oxidative stress resulting from the disproportion of oxidants and antioxidants contributes to both physiological and pathological conditions in sepsis. To combat this, the antioxidant defense system comes into the picture, which contributes to limiting the amount of reactive oxygen species (ROS) leading to the reduction of oxidative stress. However, a strong relationship has been found between scavengers of ROS and antioxidants in preclinical in vitro and in vivo models. ROS is widely believed to cause human pathology most specifically in sepsis, where a small increase in ROS levels activates signaling pathways to initiate biological processes. An inclusive understanding of the effects of ROS scavenging in cellular antioxidant signaling is essentially lacking in sepsis. This review compiles the mechanisms of ROS scavenging as well as oxidative damage in sepsis, as well as antioxidants as a potent therapeutic. Direct interaction between ROS and cellular pathways greatly affects sepsis, but such interaction does not provide the explanation behind diverse biological outcomes. Animal models of sepsis and a number of clinical trials with septic patients exploring the efficiency of antioxidants in sepsis are reviewed. In line with this, both enzymatic and non-enzymatic antioxidants were effective, and results from recent studies are promising. The usage of these potent antioxidants in sepsis patients would greatly impact the field of medicine.

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 exaggerates multiple organ injury, inflammation, and immune cell imbalance by activating the NF-κB pathway in sepsis

“…Inflammation is a key parameter of sepsis, which is mediated by the dysregulation of immune cells and release of proinflammatory cytokines ( Cecconi et al, 2018 ). Oxidative stress contributes to inflammation and organ injury during sepsis ( Kumar et al, 2022 ). Various studies have disclosed that inhibition of oxidative stress ameliorates sepsis and/or sepsis-induced multiple organ dysfunctions, including lung, liver, kidney, heart, etc ( Gong et al, 2022 ; He et al, 2022 ; Li X. et al, 2022 ; Li L. et al, 2022 ).…”

“…In addition, the markers of oxidative stress, including NO and MDA, were elevated, but the antioxidant enzyme SOD was reduced by MALT1 overexpression; however, MALT1 knockdown showed the opposite effect. These findings could be explained by the following: MALT1 could activate the NF-κB pathway ( Ekambaram et al, 2018 ); meanwhile, the NF-κB pathway critically increases the levels of inflammation and oxidative stress ( Capece et al, 2022 ; Kumar et al, 2022 ). MALT1 might promote the activation of TCR signaling, which is a vital inducer of both inflammation and oxidative stress ( Mustafa et al, 2021 ).…”

“…The NF-κB pathway is a critical signaling pathway that modulates the pathogenesis and progression of sepsis. As mentioned above, the NF-κB pathway is able to regulate cell apoptosis, inflammation, oxidative stress, and polarization of macrophages and CD4 + T cells ( Ekambaram et al, 2018 ; Kumar et al, 2022 ; Wang et al, 2022 ; Xu et al, 2022 ), which are critical mechanisms of sepsis ( Cecconi et al, 2018 ). Meanwhile, it has also been reported that the NF-κB pathway is activated in an LPS-induced septic mouse model and in septic patients ( Cao et al, 2020 ; Ke and Cai, 2021 ).…”

The role of the gut microbiome and its metabolites in cerebrovascular diseases

“…The activated TRAF6 can signal transduction by activating nuclear factor-κ B-induced kinase (NIK) and transforming growth factor β-activated kinase 1 (TAK1), and activating the corresponding NF-κB and mitogen-activated protein kinase (MAPK). Eventually, it causes the release of IL-1, IL-6, and TNF-α and participates in inflammatory reactions (Cohen, 2002;Kumar et al, 2022).…”

Biological Evaluation and Structural Analysis of Some Aminodiphenylamine Derivatives

“…All of these are highly reactive, and scholars are constantly searching for compounds that can reduce or cancel their action. In biological systems, antioxidants, such as ascorbic acid (vitamin C), polyphenols, or other amine derivatives, are known for their beneficial role in defending and sustaining cells viability [ 10 ].…”