3-Indolepropionic acid mitigates sub-acute toxicity in the cardiomyocytes of epirubicin-treated female rats.

Abstract

Epirubicin (EPI) is an effective chemotherapeutic against breast cancer, though EPI-related cardiotoxicity limits its usage. Endogenously derived 3-indolepropionic acid (3-IPA) from tryptophan metabolism is of interest due to its antioxidant capabilities which may have cardioprotective effects. Supplementation with 3-IPA may abate EPI's cardiotoxicity, and herein we studied the possibility of lessening EPI-induced cardiotoxicity in Wistar rats. Experimental rats (n = 30; BW 180-200g) were randomly distributed in five cohorts (A-E; n = 6 each). Group A (control), Group B (EPI 2.5mg/mL), and group C (3-IPA 40mg/kg) while Groups D and E were co-treated with EPI (2.5mg/mL) together with 3-IPA (D: 20 and E: 40mg/kg). Following sacrifice, oxidative status, lipid profile, transaminases relevant to cardiac function, and inflammatory biomarkers were analysed. Also, 8-hydroxyl-2'-deoxyguanosine (8-OHdG) and cardiac troponin T (cTnT) levels were assessed using an enzyme-linked immunosorbent assay (ELISA). EPI-initiated increases in cardiotoxicity biomarkers were significantly (p < 0.05) reduced by 3-IPA supplementation. Decreased antioxidant and increases in reactive oxygen and nitrogen species (RONS), 8-OHdG and lipid peroxidation were lessened (p < 0.05) in rat hearts co-treated with 3-IPA. EPI-induced increases in nitric oxide and myeloperoxidase were reduced (p < 0.05) by 3-IPA co-treatment. In addition, 3-IPA reversed EPI-mediated alterations in alanine aminotransferase (ALT), aspartate amino transaminases (AST), lactate dehydrogenase (LDH), cardiac troponin T (cTnT), and serum lipid profile including total cholesterol and triglycerides. Microscopic examination of the cardiac tissues showed that histopathological lesions severity induced by EPI was lesser in 3-IPA co-treated rats. Our findings demonstrate that supplementing endogenously derived 3-IPA can enhance antioxidant protection in the cardiac tissue susceptible to EPI toxicity in female rats. These findings may benefit breast cancer patients undergoing chemotherapy by further validating these experimental data.