Affiliation:
1. Cancer Research and Molecular Biology Laboratories, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan 200004, Nigeria
2. Department of Cancer Immunology and Biotechnology, School of Medicine, University of Nottingham, NG7 2RD, UK
3. School of Chemistry & Biochemistry, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA
Abstract
Abstract
Plant-derived phenolics are utilized as chemopreventive agents to abate adverse toxic responses associated with drug-induced damages. Tamoxifen (TAM)—a chemotherapeutic agent—is used in managing all stages of hormone-dependent breast cancer. Notwithstanding TAM’s clinical side effect—including hepatic toxicity—its use is commonplace. The present study investigates the effect of Chlorogenic acid (CGA: 25 and 50 mg kg−1; per os (p.o)) reported to exhibit various beneficial properties, including antioxidative effect against TAM (50 mg/kg; p.o.)-induced hepatorenal toxicities in rats treated as follows: Control, CGA, or TAM alone, and rats co-treated with CGA and TAM for 2 weeks. Biomarkers of hepatorenal function, oxido-inflammatory stress, and hepatorenal histopathology were performed. We observed that TAM alone decreased relative organ weights (ROW), marginally impacted rat’s survivability, and significantly (P < 0.05) increased hepatorenal toxicities and reactive oxygen and nitrogen species (RONS). TAM decreased (P < 0.05) antioxidant, anti-inflammatory cytokine (IL-10), besides increase in (P < 0.05) lipid peroxidation (LPO), pro-inflammatory cytokines (IL-1β, TNF-α), nitric oxide (NO), xanthine oxidase (XO), myeloperoxidase (MPO), and apoptotic caspases (Casp-3 and -9) levels. These biochemical alterations were accompanied by morphological lesions in experimental rats’ liver and kidney. Conversely, that CGA dose-dependently relieved TAM-mediated toxic responses, restored antioxidants capacities, reduced oxidative stress, pro-inflammatory cytokines levels, and Casp-3 and -9 activities in experimental rats. Furthermore, CGA protected against lesions observed in the liver and kidney of rats treated with TAM alone. Overall, CGA blocked TAM-mediated hepatorenal injuries associated with pro-oxidative, inflammatory, and apoptotic mechanisms. CGA may serve as a chemoprotective agent boosting patients prognosis undergoing TAM chemotherapy.
Publisher
Oxford University Press (OUP)
Subject
Health, Toxicology and Mutagenesis,Toxicology
Cited by
23 articles.
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