Albukhari Ashwag A, Gashlan Hana M, El-Beshbishy Hesham A, Nagy Ayman A, Abdel-Naim Ashraf B
Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
Food Chem Toxicol. 2009 Jul;47(7):1689-95. doi: 10.1016/j.fct.2009.04.021. Epub 2009 Apr 24.
Tamoxifen (TAM) is widely used in the treatment and prevention of breast cancer. Adverse effects of TAM include hepatotoxicity. Caffeic acid phenethyl ester (CAPE), an active component of propolis, has been used in folk medicine for diverse ailments. In the current study, the protective effects of CAPE against TAM-induced hepatotoxicity in female rats were evaluated. TAM (45 mg/kg/day, i.p., for 10 consecutive days) resulted in an elevation of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), depletion of liver reduced glutathione (GSH) and accumulation of oxidized glutathione (GSSG) and lipid peroxidation (LPO). Also, TAM treatment resulted in inhibition of hepatic activity of glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT). Further, it raised liver tumor necrosis factor-alpha (TNF-alpha) level and induced histopathological changes. Pretreatment with CAPE (2.84 mg/kg/day; i.p., for 20 consecutive days, starting 10 days before TAM injection) significantly prevented the elevation in serum activity of the assessed enzymes. CAPE significantly inhibited TAM-induced hepatic GSH depletion and GSSG and LPO accumulation. Consistently, CAPE normalized the activity of GR, GPx, SOD and CAT, inhibited the rise in TNF-alpha and ameliorated the histopathological changes. In conclusion, CAPE protects against TAM-induced hepatotoxicity.
他莫昔芬（TAM）被广泛用于乳腺癌的治疗和预防。TAM的不良反应包括肝毒性。咖啡酸苯乙酯（CAPE）是蜂胶的一种活性成分，在民间医学中用于治疗多种疾病。在本研究中，评估了CAPE对雌性大鼠TAM诱导的肝毒性的保护作用。TAM（45毫克/千克/天，腹腔注射，连续10天）导致血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）和碱性磷酸酶（ALP）升高，肝脏还原型谷胱甘肽（GSH）耗竭，氧化型谷胱甘肽（GSSG）和脂质过氧化（LPO）积累。此外，TAM治疗导致肝脏谷胱甘肽还原酶（GR）、谷胱甘肽过氧化物酶（GPx）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性受到抑制。此外，它还提高了肝脏肿瘤坏死因子-α（TNF-α）水平并诱导了组织病理学变化。CAPE预处理（2.84毫克/千克/天；腹腔注射，连续20天，从TAM注射前10天开始）显著预防了所评估酶的血清活性升高。CAPE显著抑制了TAM诱导的肝脏GSH耗竭以及GSSG和LPO积累。一致地，CAPE使GR、GPx、SOD和CAT的活性恢复正常，抑制了TNF-α的升高并改善了组织病理学变化。总之，CAPE可预防TAM诱导的肝毒性。
