The Interplay of Oxidative Stress and ROS Scavenging: Antioxidants as a Therapeutic Potential in Sepsis
Abstract
:1. Introduction
2. Oxidative Stress: Worsening the Pathology of Sepsis
3. Antioxidants as a Potential Therapy for Sepsis
3.1. Superoxide Dismutase (SOD)
3.2. Catalase
3.3. Glutathione
3.4. Vitamin C
3.5. Vitamin E
3.6. Vitamin A
3.7. N-Acetylcysteine (NAC)
3.8. Melatonin
3.9. Antioxidants Protecting Mitochondria
4. Failures and Risks of Antioxidants
5. Future Perspectives
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Oxidants (ROS) | Enzyme/Ion | Mechanism/Reaction | References |
---|---|---|---|
Superoxide radical (O2−) | NADPH oxidase | NADPH + 2O2 ➞ 2O2− + NADP+ + H+ | [15] |
Hydrogen peroxide (H2O2) | SOD | 2O2− + 2H+ ➞ H2O2 + O2 | [16] |
Hydroxyl radical (OH−) | Fe2+ | H2O2 ➞ OH− + OH. | [17] |
Hypochlorous acid (HOCl) | Myeloperoxidase | H2O2 + Cl− + H+ ➞ HOCl + H2O | [18] |
Peroxynitrite (OONO−) | NO. | NO. + O2− ➞ ONOO− | [19] |
Nitric oxide (NO.) | NOS | L-Arginine + O2 ➞ L-Citrulline + NO | [20] |
Antioxidant | Location | Mechanism | References | |
---|---|---|---|---|
Enzymatic | Superoxide dismutase | Cytoplasm, mitochondria, peroxisome, and chloroplast | O2− to O2 and H2O2 | [61,62] |
Catalase | Peroxisome and mitochondria | H2O2 to H2O and O2 | [62,63] | |
Glutathione peroxidase | Cytoplasm, mitochondria, and chloroplast | H2O2 to H2O | [64] | |
Non-enzymatic | Vitamin E (exogenous) | Cell membrane | Increases plasma NO, protects against oxidative damage induced-impaired vasorelaxation; prevents tumor initiation | [65] |
Vitamin C (exogenous) | Cytoplasm, mitochondria, peroxisome, and chloroplast | Decreases cellular oxidative damage, prevents tumor initiation; scavenging radical species; decreases pro-inflammatory cytokines; inhibition of NOx and inducible nitric oxide synthase | [49,66] | |
Vitamin A (exogenous) | Chloroplasts | NF-κβ inhibition; 10% reduction of ROS by β-carotene; upregulation of Nrf2 expression | [67,68,69] | |
N-Acetyl cysteine (NAC) (endogenous) | Administered orally or topically | Increases glutathione level in the human body; NAC acts as a methyl donor in the conversion of homocysteine to methionine | [70,71] | |
Melatonin (endogenous) | Pineal gland | Reduces the free radical generation by increasing the activity of the electron transport chain | [72] |
Vitamin | Animal Model | Tissue/ Cell | Outcomes | References |
---|---|---|---|---|
Vitamin A | Rats | Neutrophils | Reduces ROS generation by upregulating the SOD CAT, p22 and p47. | [159] |
Vitamin A | Mice | Lung | Regulates expression of cytochrome P450 | [160] |
Vitamin A | Mice | Liver | Downregulation of NF-κβ associated VCAM-1, IL-1α, MCP-1 and IFN-γ | [161] |
Vitamin A | Mice | Monoblasts | Decreased NF-κβ activity | [65] |
Vitamin E | Human | Lung | Reduces the stroke in CVD | [162] |
Vitamin E | Ex-vivo human samples | Neutrophils | Decreased O2− plasma level | [163] |
Vitamin E | Rat | Neutrophils | Induces an imbalance in hepatic vasoregulatory gene expression | [164] |
Vitamin E | Human | Whole Body | Tends to decrease LPO | [165] |
Vitamin C | Mice | Liver | Gene expression was changed | [166] |
Vitamin C | Human | Endothelial cell | Improves endothelial function | [167] |
Vitamin C | Sheep | Skin | Reduces inflammation | [113] |
Vitamin C | Human | Whole Body | Increases its serum levels, which is associated with decreased levels of CRP, PCT, and NO3−/NO2−. | [165] |
Glutathione | Rat | Mucosal tissue | Decreases glutathione concentration | [168] |
Glutathione | Human | Plasma Cells | significantly decreased the peroxidative damage of patients with septic shock | [169] |
SOD | Rat | Intestine | Increases sod concentration and decreased glutathione | [170] |
SOD mimetic (M40401) | Rat | E.coli challenged animal, blood cells | Improves the vascular reactivity, reduced cytokine production, and mortality | [72] |
SOD mimetic (MnIIITE-2-PyP5+) | Rat | Heart | Improves the vascular reactivity, reduced cytokine production, and mortality | [171] |
CAT mimetic (EUK-207) | Mice | Brain cells | Reduces the level of lipid peroxidation and oxidized nucleic acids in brain cells | [172] |
NAC | Rat | Hippocampus | Decreases the ROS activity as well as intracellular free Ca2+ | [173] |
NAC | Rat | Neural cell | Maintains the level of GSH, increases bioenergetics, and decreases oxidative damage | [174] |
NAC | Human | Whole Body | Reduces LPO and improves antioxidant capacity | [165] |
NAC | Human | Blood | Improves liver function | [137] |
NAC | Human | Blood | Decreases hepatic lactate; increases liver perfusion and function | [175] |
MitoQ | Rat | Lungs, heart, liver, gut, and kidney | Attenuation in the levels of biochemical markers of acute liver and renal dysfunction, maintenance of mitochondrial membrane potential in most organs. | [176] |
MitoQ | Rat, Mouse | Heart | Restores mitochondrial function and reduces caspase activity | [177] |
Hemigramicidin-TEMPO conjugates | Rat | Intestine | Improves the survival | [178] |
Plastoquinone decylrhodamine 19 (SkQR1), | Rat | Kidney | Increases antioxidants and shows a nephroprotective role | [179] |
MitoTEMPOL | Mouse | Diaphragm | Reduces sepsis-induced diaphragm dysfunction | [180] |
SS31 | Mouse | Restores myocardial morphological damage and suppresses inflammatory response | [181] | |
SS31 | Mouse | Diaphragm | Reduces sepsis-induced diaphragm dysfunction, and maintains mitochondrial function | [182] |
Server | Method | Sensitivity (%) | Specificity (%) | Accuracy (%) | Web-Server | Reference |
---|---|---|---|---|---|---|
AodPred | Support vector machine | 75.09 | 74.48 | 74.79 | http://lin.uestc.edu.cn/server/AntioxiPred (accessed on 1 January 2021) | [200] |
SeqSVM | Support vector machine | --- | --- | 89.46 | --- | [201] |
AOPs-SVM | Support vector machine | 68 | 98.5 | 94.2 | http://server.malab.cn/AOPs-SVM/index.jsp (accessed on 1 January 2021) | [202] |
Vote9 | Support vector machine | 65 | 99 | 94.1 | --- | [203] |
SFS-SVM | Support vector machine | --- | --- | 97.54 | https://github.com/salman-khan-mrd/Antioxident_proteins (accessed on 1 January 2021) | [204] |
AnOxPePred | Deep convolutional neural network | --- | --- | --- | http://services.bioinformatics.dtu.dk/service.php?AnOxPePred-1.0 (accessed on 1 January 2021) | [205] |
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Kumar, S.; Saxena, J.; Srivastava, V.K.; Kaushik, S.; Singh, H.; Abo-EL-Sooud, K.; Abdel-Daim, M.M.; Jyoti, A.; Saluja, R. The Interplay of Oxidative Stress and ROS Scavenging: Antioxidants as a Therapeutic Potential in Sepsis. Vaccines 2022, 10, 1575. https://doi.org/10.3390/vaccines10101575
Kumar S, Saxena J, Srivastava VK, Kaushik S, Singh H, Abo-EL-Sooud K, Abdel-Daim MM, Jyoti A, Saluja R. The Interplay of Oxidative Stress and ROS Scavenging: Antioxidants as a Therapeutic Potential in Sepsis. Vaccines. 2022; 10(10):1575. https://doi.org/10.3390/vaccines10101575
Chicago/Turabian StyleKumar, Sanni, Juhi Saxena, Vijay Kumar Srivastava, Sanket Kaushik, Himadri Singh, Khaled Abo-EL-Sooud, Mohamed M. Abdel-Daim, Anupam Jyoti, and Rohit Saluja. 2022. "The Interplay of Oxidative Stress and ROS Scavenging: Antioxidants as a Therapeutic Potential in Sepsis" Vaccines 10, no. 10: 1575. https://doi.org/10.3390/vaccines10101575
APA StyleKumar, S., Saxena, J., Srivastava, V. K., Kaushik, S., Singh, H., Abo-EL-Sooud, K., Abdel-Daim, M. M., Jyoti, A., & Saluja, R. (2022). The Interplay of Oxidative Stress and ROS Scavenging: Antioxidants as a Therapeutic Potential in Sepsis. Vaccines, 10(10), 1575. https://doi.org/10.3390/vaccines10101575