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

From: Clinical and preclinical evidence of sex-related differences in anthracycline-induced cardiotoxicity

Study Species DOX dose Major findings/proposed mechanisms
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