Premium
Epidermal growth factor receptor‐tyrosine kinase inhibition by erlotinib causes hypomagnesemia, oxidative stress and cardiac dysfunction
Author(s) -
Weglicki William B,
Mak Iu Tong,
Chmielinska Joanna J,
Spurney Christopher F,
Kramer Jay H
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1128.18
Subject(s) - hypomagnesemia , medicine , oxidative stress , erlotinib , endocrinology , nebivolol , tyrosine kinase , ejection fraction , pharmacology , heart failure , epidermal growth factor receptor , cancer , receptor , chemistry , organic chemistry , blood pressure , magnesium
We assessed cardiac dysfunction using endocardiography in rats treated with the anticancer drug erlotinib (Tarceva) at a dose of 10 mg/kg/day over a 9 week period. We observed significant progressive hypomagnesemia (P<0.05) at 5 and 9 weeks, when a 3‐fold elevation (P<0.05) of neutrophil superoxide production was seen. Moderately decreased (P<0.05) cardiac LV ejection fraction and % fractional shortening were measured at 7 weeks, and diastolic dysfunction (lower mitral valve E/A ratio) achieved significance (P<0.05) at 9 weeks of erlotinib treatment. Our prior studies with another EGFR‐TKI agent, tyrphostin AG1478 (21 mg/kg/day), also showed similar hypomagnesemia, oxidative stress, elevated plasma substance P and cardiac dysfunction after 5 weeks of treatment (Can. J. Physiol. Pharmacol. 90:1145–1149, 2012). Clinical studies have documented persistent hypomagnesemia in cancer patients treated with cetuximab (EGFR‐blocking antibody). We conclude that EGFR‐TK inhibiting agents also cause hypomagnesemia; in addition, oxidative stress and impaired cardiac contractility also occur in our rodent model. The clinical relevance of these findings with the increasing use of EGFR‐TK inhibiting drugs remains to be determined.