Substance P receptor blocker, aprepitant, inhibited cutaneous and other neurogenic inflammation side effects of the EGFR1-TKI, erlotinib
| Autor: | Joanna J. Chmielinska, I-Tong Mak, Christopher F. Spurney, William B. Weglicki, Jay H. Kramer |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Clinical Biochemistry Substance P Pharmacology Hypomagnesemia Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Erlotinib Hydrochloride 0302 clinical medicine Neurokinin-1 Receptor Antagonists medicine Animals Molecular Biology Aprepitant Neurogenic inflammation integumentary system business.industry Cell Biology General Medicine medicine.disease Hair follicle Rash Rats 030104 developmental biology medicine.anatomical_structure Hair loss chemistry 030220 oncology & carcinogenesis Erlotinib Drug Eruptions medicine.symptom Nervous System Diseases business medicine.drug |
| Zdroj: | Molecular and cellular biochemistry. 465(1-2) |
| ISSN: | 1573-4919 |
| Popis: | Cutaneous changes like rash and hair loss, as well as other neurogenic inflammation side effects, occur frequently during anticancer treatment with the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), erlotinib. These adverse events may be so severe that they impair the patient’s compliance with the treatment or even cause its discontinuation. In the current preclinical study, rats (9.2 weeks) were treated with erlotinib (10 mg/kg/day) ± aprepitant (2 mg/kg/day) for 12 weeks. Visual changes in the development of facial skin lesions/hair loss and SP-receptor expression (immunohistochemically) in facial skin tissue were assessed; also changes in plasma magnesium, 8-isoprostane, substance P (SP), neutrophil superoxide production, and cardiac function (echocardiography) were measured. Erlotinib lowered plasma magnesium 14%, elevated SP 65%, caused 3.7-fold higher basal superoxide production, 2.5-fold higher 8-isoprostane levels, 11.6% lower cardiac systolic, and 10.9% lower diastolic function. Facial dermatological changes (alopecia, skin reddening, scabbing, nose crusting) occurred by 4 weeks (± + to ++) in erlotinib-treated rats, and progressively worsened (±++ to +++) by week 12. Facial skin SP-receptor upregulation (78% higher) occurred in epidermal and hair follicle cells. All adverse effects were substantially and significantly mitigated by aprepitant, including a 62% lowering of skin SP-receptors (p |
| Databáze: | OpenAIRE |
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