Table 3 Sex-related differences in anthracycline-induced cardiomyopathy in preclinical adult animal models

Julicher et al. [76]

Adult Lou/M Wsl rats

Chronic

1 mg/kg for 5 consecutive days, then weekly

Female rats were protected from DOX-induced cardiotoxicity, nephrotoxicity, and hepatotoxicity.

van Almen et al. [86]

Adult WT and thrombospondin-2 KO mice

Chronic

2 mg/kg/week for 12 weeks

Female sex protected against DOX-induced myocardial fibrosis in the KO mice.

Zhang et al. [66]

Adult SHR

Chronic

1 mg/kg/week for 9, 10, or 12 weeks

Female sex is protected against DOX-induced cardiotoxicity and nephrotoxicity. Ovariectomy prevented this protection.

Mechanism: cardiac mast cells activity

Moulin et al. [61]

Adult Wistar rats

Chronic

2 mg/kg/week for 7 weeks

Female sex protected against DOX-induced cardiotoxicity. No mortality in females, up to 50% mortality in males.

Mechanism: mitochondrial dysfunction and AMPK signaling

Moulin et al. [62]

Adult Wistar rats

Chronic

2 mg/kg/week for 7 weeks

Sexual dimorphism of cardiac phospholipid content

Gonzalez et al. [64]

Adult SST-2 tumor-bearing SHR

Acute

10 mg/kg once

Adult tumor-bearing male SHRs are more cardiosensitive to Dox than female or hormone-deficient animals

Zordoky et al. [67]

Adult WKY and SHHF rats

Chronic

2 mg/kg/week for 8 weeks

Female sex protected against DOX-induced hypertension in WKY rats and protected against DOX-induced cardiac dysfunction in SHHF rats. Female sex protected against DOX-induced nephrotoxicity in both strains.

Jenkins et al. [65]

Young adult B6C3F1 mice (8 weeks)

Chronic

3 mg/kg/week for 6, 7, 8, and 9 weeks

Female sex protected against DOX-induced myocardial injury

Grant et al. [68]

Adult C57Bl/6 mice

Acute 20 mg/kg once

Adult male mice are more susceptible to DOX-induced cardiotoxicity. Possible involvement of CYP450 differential expression