Preventive effect of Diallyl Trisulfide on cutaneous toxicities induced by EGFR inhibitor

Int Immunopharmacol. 2019 Apr:69:79-87. doi: 10.1016/j.intimp.2019.01.023. Epub 2019 Jan 23.

Abstract

Cutaneous toxicities are the commonest side effects in patients with cancer treated using epidermal growth factor receptor inhibitors such as erlotinib. For patients with such toxicities, there is a lack of safe, effective pharmacological agents. Here we established a skin toxicity model and investigated the preventive and therapeutic effect of Diallyl Trisulfide (DATS) in vivo. The mouse skin toxicities model was established through continuous administration of erlotinib for 49 days. Meanwhile, the mice in the experimental group underwent DATS treatment for 49 days. Hematoxylin and eosin (HE) staining and oil red O staining of back and limb skin was performed to determine whether DATS aqueous extract can reverse the skin toxicities caused by erlotinib. Compared with the erlotinib group, the incidence of rash in the DATS group was lower. In addition, in the DATS group, the degree of skin redness and herpes was mild, the body weight was stable, and the activity was favorable. By comparing the HE and oil red O staining results for the mouse skin, the degree of keratin hyperplasia was determined to be lower in the experimental group than in the erlotinib group, and the number of purulent neutrophils decreased. The number of follicles was relatively less. The release of TNF-α, IL-6 and other inflammatory factors was reduced by DATS. Erlotinib hydrochloride can cause severe skin toxicities, and DATS prevents skin toxicities, its mechanism may be related to DATS reduced erlotinib-induced inflammatory injury.

Keywords: Cutaneous toxicities; DATS; EGFRIs; Inflammatory.

MeSH terms

  • Allyl Compounds / therapeutic use*
  • Animals
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Disease Models, Animal
  • Drug-Related Side Effects and Adverse Reactions / prevention & control*
  • ErbB Receptors
  • Erlotinib Hydrochloride / adverse effects*
  • Erlotinib Hydrochloride / therapeutic use
  • Exanthema / etiology
  • Exanthema / prevention & control*
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms / drug therapy*
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use
  • Skin / drug effects*
  • Skin / pathology
  • Sulfides / therapeutic use*

Substances

  • Allyl Compounds
  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Sulfides
  • diallyl trisulfide
  • Erlotinib Hydrochloride
  • EGFR protein, human
  • ErbB Receptors