Epirubicin toxicity in rat's ovary and uterus: A protective role of 3-Indolepropionic acid supplementation

Chem Biol Interact. 2023 Apr 1:374:110414. doi: 10.1016/j.cbi.2023.110414. Epub 2023 Feb 21.

Abstract

The "anthracycline, Epirubicin (EPI)," in managing breast cancer, is highly cytotoxic. Tryptophan-derived 3-indolepropionic acid (3-IPA) decreases oxidative damage, and its prospect of alleviating EPI-induced cytotoxicity was examined in rats' hypothalamus-ovary-uterus axis. Female rats: Control, EPI (2.5 mg/kg), 3-IPA alone (40 mg/kg), EPI+3-IPA (2.5 mg/kg + 20 mg/kg), EPI + 3-IPA2 (2.5 mg/kg + 40 mg/kg) were treated for 28 days. Subsequently, reproductive hormones, oxidative and inflammatory stress biomarkers, and tissue histology were examined. 3-IPA prevented EPI-induced decreases in the follicle-stimulating hormone, estradiol, progesterone and prolactin levels. EPI-mediated reduction in antioxidant enzymes, reduced glutathione and total sulfhydryl groups were partially counteracted by 3-IPA co-treatment. Increased oxidative and inflammatory stress biomarkers caused by treatment with EPI alone were lessened by 3-IPA co-treatment. Also, 3-IPA reduced histological damage in the examined tissues. Conclusively, 3-IPA ameliorated biochemical markers and tissue injury caused by EPI treatment alone via an antioxidative and anti-inflammatory mechanism while stabilising serum hormone dynamics.

Keywords: 3-Indolepropionic acid; Endogenously-derived antioxidants; Epirubicin; Oxido-inflammatory stress; Reproductive hormones; Toxicity.

MeSH terms

  • Animals
  • Antioxidants* / metabolism
  • Antioxidants* / pharmacology
  • Biomarkers / metabolism
  • Dietary Supplements
  • Epirubicin / metabolism
  • Epirubicin / toxicity
  • Female
  • Follicle Stimulating Hormone
  • Ovary* / pathology
  • Oxidative Stress
  • Rats
  • Rats, Wistar
  • Uterus / metabolism

Substances

  • Epirubicin
  • 3-(indol-3-yl)propionic acid
  • Antioxidants
  • Follicle Stimulating Hormone
  • Biomarkers