E Owumi Solomon, K Olusola Joseph, O Arunsi Uche, K Oyelere Adegboyega
Cancer Research and Molecular Biology Laboratories, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan 200004, Nigeria.
Department of Cancer Immunology and Biotechnology, School of Medicine, University of Nottingham, NG7 2RD, UK.
Toxicol Res (Camb). 2021 Feb 13;10(2):345-353. doi: 10.1093/toxres/tfab002. eCollection 2021 Mar.
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; )) reported to exhibit various beneficial properties, including antioxidative effect against TAM (50 mg/kg; .)-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 () increased hepatorenal toxicities and reactive oxygen and nitrogen species (RONS). TAM decreased () antioxidant, anti-inflammatory cytokine (IL-10), besides increase in ( 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.
植物源酚类化合物被用作化学预防剂,以减轻与药物诱导损伤相关的不良毒性反应。他莫昔芬(TAM)——一种化疗药物——用于治疗激素依赖性乳腺癌的各个阶段。尽管TAM存在包括肝毒性在内的临床副作用,但其使用仍很普遍。本研究调查了绿原酸(CGA:25和50毫克/千克)的作用,据报道CGA具有多种有益特性,包括对TAM(50毫克/千克)诱导的肝肾毒性的抗氧化作用。对大鼠进行如下处理:单独的对照组、CGA组、TAM组,以及CGA和TAM联合处理2周的组。检测了肝肾功 能、氧化炎症应激和肝肾组织病理学的生物标志物。我们观察到,单独使用TAM会降低相对器官重量(ROW),对大鼠的存活率有轻微影响,并显著增加肝肾毒性以及活性氧和氮物种(RONS)。TAM降低了抗氧化剂、抗炎细胞因子(IL-10),同时增加了(P<0.05)脂质过氧化(LPO)、促炎细胞因子(IL-1β、TNF-α)、一氧化氮(NO)、黄嘌呤氧化酶(XO)、髓过氧化物酶(MPO)和凋亡半胱天冬酶(Casp-3和-9)的水平。这些生化改变伴随着实验大鼠肝脏和肾脏的形态学损伤。相反,CGA剂量依赖性地减轻了TAM介导的毒性反应,恢复了抗氧化能力,降低了氧化应激、促炎细胞因子水平以及实验大鼠中Casp-3和-9的活性。此外,CGA预防了单独用TAM处理的大鼠肝脏和肾脏中观察到的损伤。总体而言,CGA阻断了与促氧化、炎症和凋亡机制相关的TAM介导的肝肾损伤。CGA可能作为一种化学保护剂,改善接受TAM化疗患者的预后。