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February 14, 2020International Journal of Molecular SciencesOpen Access

Sexual Dimorphism in Doxorubicin-induced Systemic Inflammation: Implications for Hepatic Cytochrome P450 Regulation

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Why the study?

Sex differences in doxorubicin-induced systemic inflammation and the potential effects on hepatic cytochrome P450 expression had not been determined.

Population

Male and female C57Bl/6 mice

Comparison

DOX (20 mg/kg by intraperitoneal injection) evaluated across sexes

Design

Preclinical animal study

Follow-up

24 and 72 h

Authors

MGMarianne GrantIAIbrahim Y. AbdelgawadCLChristine A. Lewis

Discussion

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Overview

May support sex-specific DOX monitoring in cardio-oncology; leaves open prospective validation of CYP effects.

Key Points

  • To determine sex differences in doxorubicin-induced systemic inflammation and assess their downstream effects on hepatic cytochrome P450 enzyme expression.
  • Administered doxorubicin at 20 mg/kg via intraperitoneal injection to male and female C57Bl/6 mice.
  • Sacrificed cohorts at 24 and 72 hours post-treatment to evaluate systemic inflammatory response and hepatic cytochrome P450 isoform expression levels.
  • Doxorubicin triggered systemic inflammation across both sexes, but the response was substantially more pronounced in male mice than in female mice.
  • Hepatic CYP expression was altered in a sex-dependent pattern, showing significantly greater suppression of Cyp2c29 and Cyp2e1 in males that mirrored systemic inflammation severity.

Structured PICO

P
Population
Male and female C57Bl/6 mice
I
Intervention
Doxorubicin (20 mg/kg by intraperitoneal injection)
O
Outcome
Systemic inflammatory response and expression of hepatic cytochrome P450 (CYP) isoformssurrogate

Sex differences in doxorubicin-induced systemic inflammation and hepatic CYP inhibition may contribute to sexually dimorphic drug interactions and organ toxicity.

Cite This Study

Grant et al. (2020) studied this question.

synapsesocial.com/papers/6a6ff6206c240de38cdba29ahttps://doi.org/10.3390/ijms21041279
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Also Consider

Synapse has enriched 4 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Sex-related Differences in Mast Cell Activity and Doxorubicin Toxicity2013 · 54 citations
  2. 2Doxorubicin Administration by Continuous Infusion Is Not Cardioprotective: The Dana-Farber 91-01 Acute Lymphoblastic Leukemia Protocol2002 · 179 citations
  3. 3Highly potent visnagin derivatives inhibit Cyp1 and prevent doxorubicin cardiotoxicity2018 · 41 citations
  4. 4Milk diets influence doxorubicin-induced intestinal toxicity in piglets2016 · 17 citations