Chlorogenic acid abates oxido-inflammatory and apoptotic responses in the liver and kidney of Tamoxifen-treated rats

被引:31
作者
Owumi, Solomon E. [1 ]
Olusola, Joseph K. [1 ]
Arunsi, Uche O. [2 ]
Oyelere, Adegboyega K. [3 ]
机构
[1] Univ Ibadan, Coll Med, Fac Basic Med Sci, Canc Res & Mol Biol Labs,Dept Biochem, Ibadan 200004, Nigeria
[2] Univ Nottingham, Sch Med, Dept Canc Immunol & Biotechnol, Nottingham NG7 2RD, England
[3] Georgia Inst Technol, Parker H Petit Inst Bioengn & Biosci, Sch Chem & Biochem, Atlanta, GA 30332 USA
关键词
Tamoxifen; chlorogenic acid; hepatorenal toxicity; oxido-inflammatory stress; antioxidant; apoptosis; TOLL-LIKE RECEPTORS; OXIDATIVE STRESS; POTENTIAL ROLE; GLUTATHIONE; EXPRESSION; INJURY; BIOMARKERS; METABOLISM; MECHANISMS; SYNTHASE;
D O I
10.1093/toxres/tfab002
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
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-1 beta, TNF-alpha), 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.
引用
收藏
页码:169 / 182
页数:14
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