ArticleBiology of sex differences2017
Sex-dependent alteration of cardiac cytochrome P450 gene expression by doxorubicin in C57Bl/6 mice.
Article in Biology of sex differences, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 51 citations in OpenAlex.
- Colonoid-Based Transcriptomics Reveals Conserved and Model-Specific Mechanisms of Doxorubicin-Induced Intestinal Toxicity.International journal of molecular sciences · 2026Article
- Hepatic Effects of Etoricoxib in Mice: Integrated Histopathological and Gene Expression Analysis.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Mechanisms and the Role of p38 MAPK Signaling in Doxorubicin-Induced Cardiotoxicity: A Review.International journal of general medicine · 2026Review
- The Protective Effects of Carvacrol Against Doxorubicin-Induced Cardiotoxicity In Vitro and In Vivo.Cardiovascular toxicology · 2025Article
- Doxorubicin-Induced Cardiotoxicity Through SIRT1 Loss Potentiates Overproduction of Exosomes in Cardiomyocytes.International journal of molecular sciences · 2024Article
- Sex Differences in the Development of Anthracycline-Associated Heart Failure.Journal of cardiac failure · 2024Article
- Effect of acute high-intensity interval exercise on a mouse model of doxorubicin-induced cardiotoxicity: a pilot study.BMC sports science, medicine & rehabilitation · 2024Article
- Sex-related differences in delayed doxorubicin-induced cardiac dysfunction in C57BL/6 mice.Archives of toxicology · 2024Article
- Exposure to Doxorubicin Modulates the Cardiac Response to Isoproterenol in Male and Female Mice.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Sex-Specific Cardiovascular Risks of Cancer and Its Therapies.Circulation research · 2022Review
- Inter-Individual Variation and Cardioprotection in Anthracycline-Induced Heart Failure.Journal of clinical medicine · 2021Review
- Consideration of Sex as a Biological Variable in the Development of Doxorubicin Myotoxicity and the Efficacy of Exercise as a Therapeutic Intervention.Antioxidants (Basel, Switzerland) · 2021Review
- CYP1B1 as a therapeutic target in cardio-oncology.Clinical science (London, England : 1979) · 2020Article
- Sexual Dimorphism in Doxorubicin-induced Systemic Inflammation: Implications for Hepatic Cytochrome P450 Regulation.International journal of molecular sciences · 2020Article
- Lack of sexual dimorphism in a mouse model of isoproterenol-induced cardiac dysfunction.PloS one · 2020Article
- Article
- Clinical and preclinical evidence of sex-related differences in anthracycline-induced cardiotoxicity.Biology of sex differences · 2018Review
- Co-administration of resveratrol with doxorubicin in young mice attenuates detrimental late-occurring cardiovascular changes.Cardiovascular research · 2018Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThere is inconclusive evidence about the role of sex as a risk factor for doxorubicin (DOX)-induced cardiotoxicity. Recent experimental studies have shown that adult female rats are protected against DOX-induced cardiotoxicity. However, the mechanisms of this sexual dimorphism are not fully elucidated. We have previously demonstrated that DOX alters the expression of several cytochrome P450 (CYP) enzymes in the hearts of male rats. Nevertheless, the sex-dependent effect of DOX on the expression of CYP enzymes is still not known. Therefore, in the present study, we determined the effect of acute DOX exposure on the expression of CYP genes in the hearts of both male and female C57Bl/6 mice.
methodsAcute DOX cardiotoxicity was induced by a single intraperitoneal injection of 20 mg/kg DOX in male and female adult C57Bl/6 mice. Cardiac function was assessed 5 days after DOX exposure by trans-thoracic echocardiography. Mice were euthanized 1 day or 6 days after DOX or saline injection. Thereafter, the hearts were harvested and weighed. Heart sections were evaluated for pathological lesions. Total RNA was extracted and expression of natriuretic peptides, inflammatory and apoptotic markers, and CYP genes was measured by real-time PCR.
resultsAdult female C57Bl/6 mice were protected from acute DOX-induced cardiotoxicity as they show milder pathological lesions, less inflammation, and faster recovery from DOX-induced apoptosis and DOX-mediated inhibition of beta-type natriuretic peptide. Acute DOX exposure altered the gene expression of multiple CYP genes in a sex-dependent manner. In 24 h, DOX exposure caused male-specific induction of Cyp1b1 and female-specific induction of Cyp2c29 and Cyp2e1.
conclusionsAcute DOX exposure causes sex-dependent alteration of cardiac CYP gene expression. Since cardiac CYP enzymes metabolize several endogenous compounds to biologically active metabolites, sex-dependent alteration of CYP genes may play a role in the sexual dimorphism of acute DOX-induced cardiotoxicity.
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