Table 1.

List of therapies under investigation for mucositis development prevention grouped accordingly to their mechanism of action

Antioxidant agents	Characteristics	Mechanism of action	References
Amifostine	Phosphorylated aminosulfhydryl compound	Promotes recruitment of ROS scavenger, reduces DNA strand breaks	[65, 66]
Glutamine	Amino acid	Exerts antioxidant activities promoting glutathione synthesis	[67–71]
Oral zinc supplement	Essential mineral	Prevents lipids peroxidation, replaces redox reactive metals, induces metallothionein synthesis	[72–77]
Vitamin E	Lipid soluble α-tocopherol	Prevents tissue damages caused by the ROS release	[78–80]
N-acetyl-cysteine	N-acetyl derivative of the natural amino acid L-cysteine	Exerts antioxidant activities promoting glutathione synthesis, myeloperoxidase activity, xanthine dehydrogenase and oxidase activity.	[81, 82]
GC4419	Synthetic manganese-based drug	Counteracts superoxide dismutase activity	[83]
Inhibitors of inflammation and cytokines production	Characteristics	Mechanism of action	References
Turmeric	Flowering plant belonging to Curcuma longa	Counteracts NF- κB activiy	[84]
Clonidine lauriad mucoadhesive buccal tablets	Tablets contain high concentrations of an anti-inflammatory active principle (clonidine)	Inhibits NF-κB activity and the downstream pro-inflammatory cytokines-mediated signal	[85]
SMAD7 over expression	Gene encoding the nuclear protein Smad7 that binds the E3 ubiquitin ligase SMURF2	Impairs TGF-β1 that NF-κB activities in mice model (K5.Smad7) irradiated	[86]
Benzydamine hydrochloride rinses	Indazole non-steroidal anti-inflammatory drug	Inhibits the activity and the production of pro-inflammatory cytokines, TNF-α and IL-1β	[87, 88]
Pentoxifylline	Xanthine derivative	Impairs NF-κB activity and inhibits TNF-α and IL-1β action	[89, 90]
Dusquetide (SGX942)	5-amino acid innate defence regulator (IDR) peptide	Modulates immune innate pro-inflammatory response	[91]
Multi target natural agents	Characteristics	Mechanism of action	References
Honey	Honey topical application	Attenuates burns and pressure wounds.	[92–95]
Manuka and Kanuka essential oils	Mix of essential oil from Leptospermum scoparium and Kunzea ericoides	Anti-inflammatory, analgesic and anti-micotic and -bacterial activities	[96]
Chinese traditional herbs	1-Extract of Indigowood root 2-Extract of Rhodiola algida	1-Anti-inflammatory and antiviral activities 2-Stimulates the immuno system	[97, 98]
Chamomile mouthwash	infusion of powdered flower in water	Anti-inflammatory, analgesic and anti-micotic and -bacterial activities	[99, 100]
Aloe vera gel	Juice of succulent plant species of the genus Aloe	Promotes wound healing	[101]
MF 5232 (Mucotrol®)	Oral poliherbal gel wafer	Analgesic, wound healing and anti oxidant properties	[102]
Traumeel S®	Homeophatic complex mouthwash	Unknown mechanism of action	[103]
Physical intervention	Characteristics	Mechanism of action	Reference
Low-levels laser therapy (LLLT)	Monochromatic laser at low intensity	Promotes regeneration of damaged-tissue	[73, 83]
Oral cryotherapy	ice chips, ice cubes, ice lollipops	Promotes local vasoconstriction, thus leading to a reduction exposure of mucosa to chemotherapy	[73, 81, 104]
Oral care	Standardized oral care and frequent oral cavity examination by oral care experts	Prevents infections	[105]
Lactobacillus	Probiotic	Preserves mucosal intestinal architecture	[106, 107]