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Gender is a factor that can impact the severity of doxorubicin (DXR) toxicity in spontaneously hypertensive rats (SHR)
Author(s) -
Herman Eugene,
Knapton Alan,
Zhang Jun,
Hiraragi Hajime,
Lipshultz Steven
Publication year - 2008
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.22.1_supplement.719.6
Subject(s) - medicine , cardiotoxicity , doxorubicin , endocrinology , lesion , toxicity , blood urea nitrogen , adult male , chemotherapy , kidney , pathology
Female pediatric patients appear to be more susceptible to doxorubicin cardiotoxicity than males. The present study sought to determine whether gender affects the severity of DXR‐induced cardiac and non cardiac tissue toxicity. Male and female SHR (14 weeks of age)(15/group) were administered 1 mg/kg DXR (iv) weekly for 9, 10 or 12 weeks. The study was terminated 1 week after the final dose. Four male SHR died after 9 or 10 DXR doses. Weight gain was retarded to a greater extent in DXR‐treated male than female SHR (5% of male control vs 46% of female control). Serum levels of urea nitrogen (BUN) were elevated only in male SHR (↑220–250%).Changes in serum concentration, over pretreatment levels, of cholesterol (↑630–960% vs 200–520% female), triglycerides (↑910–1790% vs 600% female) and albumin (↓75–77% vs 15–50% female) were significantly more profound in the DXR‐treated male SHR. DXR‐induced myocardial alterations were more severe in male (avg lesion score=2.3) compared to female SHR (avg lesion score=1.5)(p<0.01). Serum levels of cardiac troponin T were significantly higher in male (avg 0.62 ng/ml) than female (avg 0.10 ng/ml)(p<0.01). DXR caused more severe renal lesions in male (avg lesion score=3.9) than in female (avg lesion score=2.2) SHR (p<0.01). The findings in adult male SHR imply that gender can play a significant role in the susceptibility of various tissues, such as the heart, to the toxic effects of DXR.