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

• Published in: Chemico-biological interactions Vol. 374; p. 110414
• Main Authors: Owumi, Solomon E., Adebisi, Grace E., Odunola, Oyeronke A.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.04.2023
• Subjects: 3-Indolepropionic acid; Animals; Antioxidants - metabolism; Antioxidants - pharmacology; Biomarkers - metabolism; Dietary Supplements; Endogenously-derived antioxidants; Epirubicin; Epirubicin - metabolism; Epirubicin - toxicity; Female; Follicle Stimulating Hormone; Ovary - pathology; Oxidative Stress; Oxido-inflammatory stress; Rats; Rats, Wistar; Reproductive hormones; Toxicity; Uterus - metabolism; 3-Indolepropionic acid; Reproductive hormones; Epirubicin; Oxido-inflammatory stress; Toxicity; Endogenously-derived antioxidants
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2023.110414

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. •Epirubicin (EPI) -an anthracycline drug class–is used in treating breast cancer.•Tryptophan metabolite -Indole-3propanioc acid (3-IPA), abates oxidative damage.•3-IPA prevented EPI-induced decrease in female rat reproductive hormones.•3-IPA abated EPI-mediated oxidative stress, lipid peroxidation and inflammation.•3-IPA abated EPI-induced hypothalamic, ovarian and uterine histological alterations.