Pro-Inflammatory Signalling PRRopels Cisplatin-Induced Toxicity
Abstract
:1. Introduction
Inflammation and Pro-Inflammatory Signalling
2. Pattern Recognition Receptors (PRRs) in Cisplatin-Induced Toxicities
2.1. Toll-Like Receptors (TLRs)
2.2. NOD-Like Receptors (NLRs) and Inflammasomes
3. Pro-Inflammatory Messengers (Cytokines and Chemokines)
4. Oxidative Stress and Immunologic Regulation
5. Anti-Inflammatory Remedies
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Classification | Name | Anti-Inflammatory Mechanism(s) of Action | Targeted CITs | Reference(s) |
---|---|---|---|---|
Non- Flavonoid Polyphenol Phytoalexin | Resveratrol | Inhibits TLR4 Signalling Inhibits IL-6, TNF-α, Inhibits NF-κB Signalling Radical Scavenging Metal Chelation | CIO CIOV (Ovarian) CIU (Uterine) CIN | [165,166,167,168,169,170,171,172,173,174,175,176] |
Bee Products | Honey | Inhibits IL6, TNF-α, MCP-1, ICAM1 | CIN | [177] |
Caffeic Acid | Radical Scavenging | CIO | [178] | |
Bee Pollen Extract | Inhibits IL6, IL1β Inhibits NF-κB Signalling | CIN CIH | [179] | |
Mellit (Bee Venom) | Inhibits IL-6, IL-1β, TNF-α Upregulates IL-10 Alters/Inhibits Mθ Invasion Enhanced T-Reg Activity Inhibits COX2 | CIN CIPN (Potential) | [180,181,182] | |
Flavonoid | Curcumin | Inhibits IL-6, IL-1β, TNF-α, MCP-1 Upregulates/maintains IL-10 Free Radical Scavenging Inhibits COX Inhibits JAK/STAT Signalling Inhibits NF-κB Signalling | CIN CIO CIPN CIH | [183,184,185,186,187,188,189,190,191,192,193] |
Epigallocatechin Gallate (EGCG) | Inhibits MAPK Signalling Dis-regulates STAT1/STAT3 Signalling Inhibits IL-6, IL-1β, TNF-α Inhibits NF-κB Signalling Upregulates Nrf2 | CIN CIH CICN (Cerebral Neurotoxicity) | [194,195,196,197,198,199] | |
Quercetin | Inhibits NF-κB Signalling Potential COX Inhibition Potential iNOS Inhibition | CIO CIN | [200,201,202,203,204,205] | |
Baicalein | Inhibits IL-6, TNF-α Inhibits NF-κB Inhibits TLR-2, TLR-4 Signalling Upregulates Nrf2 Upregulates HO-1 | CIN | [93,206] | |
Wogonin | Inhibits IL-6, IL-8, IL-1β, MCP-1, TNF-α Inhibits NF-κB Signalling Inhibit COX2 | CIN | [207,208,209] | |
Glycyrrhizic Acid (Licorice) | Inhibits IL-1β, TNF-α Inhibits NF-κB Signalling Reduces DAMP Release | CIN CIH | [210,211,212] | |
Hesperetin | Inhibits MAPK Signalling Upregulates TNF-α Signal Inhibitor Upregulates Nrf2 Upregulates HO-1 | CIN | [213] | |
D-Pinitol | Inhibits IL-6, IL-1β, TNF-α | CIN | [214] | |
Sappanone A | Inhibits IL-6, IL-1β, TNF-α Inhibits NF-κB Signalling Inhibits COX2 Upregulates Nrf2 | CIN | [215,216,217] | |
Xanthohumol | Inhibits IL-6, IL-1β, TNF-α Inhibits TLR4 Expression Inhibits NF-κB Signalling | CIN | [218] | |
Puerarin | Inhibits IL-6, TNF-α Inhibits TLR4 Signalling Inhibits ΝF-κB | CIN CIO | [219,220] | |
Icariin | Inhibits IL-1β, TNF-α Inhibits NF-κΒ Signalling Inhibits iNOS | CIN | [221,222] | |
Genistein | Inhibits ICAM-1, MCP-1 Inhibits Mθ Infiltration Inhibits NF-κB Signalling | CIN CIO | [223,224] | |
Galangin | Inhibits IL-6, IL-1β, TNF-α Inhibits MAPK Signalling Inhibits NF-κΒ Signalling | CIN | [225,226] | |
Luteolin | Inhibits TNF-α Inhibits NF-κB Signalling Inhibits COX2 | CIN | [227] | |
Saponins | Ginsenosides (Several) | Inhibit IL-1β, TNF-α Inhibit NF-κB Signalling Inhibit COX2 Inhibit iNOS | CIN CIO | [228,229,230,231,232,233] |
Alkaloids | Berberine | Inhibits IL-6, IL-1β, TNF-α Inhibits MAPK Signalling Inhibits NF-κB Signalling Upregulates IL-10 s Antioxidant Effect (Reduced ROS Generation) | CIPN CIO | [234,235] |
Betaine | Inhibits IL-6, IL-1β, TNF-α Inhibits NF-κB Signalling | CIN | [236,237] | |
Tetramethylpyrazine | Inhibits IL-1β, TNF-α Inhibits TLR4 Signalling Reduces DAMP Release Upregulates Nrf2s | CIN CIO (Potential) | [238,239] | |
Other Natural Compounds | Astragaloside | Inhibits IL-1β, TNF-α Inhibits Caspase-1 & NLRP3 Inhibits NF-κB Signalling Upregulates Nrf2 | CIN | [113,240] |
Sinapic Acid | Inhibits IL-6, IL-1β, TNF-α Inhibits NF-κB Signalling Upregulates Nrf2 Upregulates HO-1 | CIN | [241,242] | |
Vanillin | Inhibits IL-18, TNF-α Inhibits NF-κB Signalling Inhibits iNOS Upregulates IL-10 Upregulates Nrf2 | CIN | [243,244] |
Classification | Name | Anti-Inflammatory Mechanism(s) of Action | Targeted CITs | Reference(s) |
---|---|---|---|---|
Anti-Inflammatory (Iridoid Glycoside) | Aucubin | Inhibits TNF-α Inhibits STAT3/MAPK Signalling Inhibits NF-κB Signalling Upregulates HO-1 | CIN | [245] |
Anti-Inflammatory (COX2 Inhibitor) | Etoricoxib | Inhibits TNF-α Inhibits iNOS Inhibits COX2 | CIN | [173] |
Anti-Inflammatory (Clove Oil) | Eugenol | Inhibits IL-6, TNF-α Inhibits COX2 | CIO CIN CITT (Testicular) | [246,247,248,249] |
Anti-Inflammatory (Iridoid Monoterpinoid) | Monotropein | Upregulated HO-1 Upregulated Nrf2 | CIN | [250,251,252] |
Anti-Inflammatory (Synthetic Luteolin) | Isoorientin | Inhibits MAPK Signalling Reduces DAMP Release Inhibits NF-κB Signalling Upregulated HO-1 Upregulates Nrf2 | CIN | [253] |
Anti-Inflammatory (Calcium Antagonist) | Flunarizine | Inhibits IL-6, IL-1β, TNF-α Inhibits MAPK Signalling Inhibits NF-κB Signalling Upregulates Nrf2 Upregulates HO-1 | CIO CIUN (Uremic Neuropathy) | [75,254,255,256] |
Anti-Inflammatory | R-Phenylisopropyladenosine (R-PIA) | Inhibits TNF-α Inhibits MAPK Signalling Inhibits STAT1 Signalling Inhibits iNOS Inhibits COX2 | CIO | [257] |
Solubilised Membrane Protein | Thrombomodulin Alfa | Thrombin-Mediated DAMP Degradation | Chemotherapy-IPN | [258,259,260] |
Anti-Inflammatory (Nrf2 Activator) | Dimethyl Fumarate | Inhibits Immune Cell Infiltrations Upregulation of Nrf2s Inhibits IL-6, IL4, IL-10, TNF-α | Chemotherapy-IPN CIPNs CIN | [261,262,263] |
Clinical Trial Status | Intervention (Name) | Mechanism(s) of Action | Listed Target Condition (CIT) | Additional Reference(s) |
---|---|---|---|---|
Recruiting | N-Acetylcysteine | Antioxidant | CIO (CIN) | [266,267,268,269] |
Terminated | Sodium Thiosulfate (Trans-Tympanic Gel) | Antioxidant | CIO | [270,271] |
Completed | Ginkgo Biloba Extract (GBE761) | Antioxidant Anti-Inflammatory | CIO | [272,273,274,275] |
Completed | Sodium Thiosulfate | Antioxidant | CIO | [270,271] |
Not Recruiting | Sodium Thiosulfate (+Mannitol) | Antioxidant | CIO | [270,271] |
Recruiting | Rosuvastatin | Cholesterol Reduction (HMG-CoA Inhibition) Antioxidant Anti-Inflammatory | CIO CIN | [276,277,278,279,280,281,282] |
Completed | Dexamethasone (Synthetic Corticosteroid) | Anti-Inflammatory Antioxidant | CIO | [283,284,285,286,287,288] |
Terminated | OTO-104 (Dexamethasone Hydrogel) | Anti-Inflammatory Antioxidant | CIO | [289] |
Recruiting | Tempol (SOD and Catalase Mimetic) | Antioxidant | CIN CIO | [290,291,292,293] |
Completed | Silymarin | Antioxidant Anti-Inflammatory | CIN | [294,295,296] |
Completed | Mannitol (Intravenous) | Osmotic Diuretic | CIN | [297,298,299,300] |
Completed | Preloaded Magnesium | Homeostatic Cisplatin Efflux Regulation (Downregulated Transporters) | CIN | [301,302,303,304,305,306] |
Completed | Acetazolamide + Mannitol, (+N-Acetylcysteine) | Alkaline Diuretic (Carbonic Anhydrase Inhibitor) | CIN | [307,308] |
Recruiting | Pantoprazole | Cisplatin Influx Regulation (OCT2 Inhibitor) Anti-Inflammatory | CIN | [309,310] |
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Domingo, I.K.; Latif, A.; Bhavsar, A.P. Pro-Inflammatory Signalling PRRopels Cisplatin-Induced Toxicity. Int. J. Mol. Sci. 2022, 23, 7227. https://doi.org/10.3390/ijms23137227
Domingo IK, Latif A, Bhavsar AP. Pro-Inflammatory Signalling PRRopels Cisplatin-Induced Toxicity. International Journal of Molecular Sciences. 2022; 23(13):7227. https://doi.org/10.3390/ijms23137227
Chicago/Turabian StyleDomingo, Ivan K., Asna Latif, and Amit P. Bhavsar. 2022. "Pro-Inflammatory Signalling PRRopels Cisplatin-Induced Toxicity" International Journal of Molecular Sciences 23, no. 13: 7227. https://doi.org/10.3390/ijms23137227