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Table 1 List of therapies under investigation for mucositis development prevention grouped accordingly to their mechanism of action

From: Oral mucositis: the hidden side of cancer therapy

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

[67,68,69,70,71]

Oral zinc supplement

Essential mineral

Prevents lipids peroxidation, replaces redox reactive metals, induces metallothionein synthesis

[72,73,74,75,76,77]

Vitamin E

Lipid soluble α-tocopherol

Prevents tissue damages caused by the ROS release

[78,79,80]

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.

[92,93,94,95]

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]