Ibrahim A B, Mansour H H, Shouman S A, Eissa A A, Abu El Nour S M
Department of Pharmacology, Faculty of Medicine, Zawia University, Libya.
Department of Health Radiation Research, National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt.
Hum Exp Toxicol. 2014 Sep;33(9):968-79. doi: 10.1177/0960327113506237. Epub 2013 Dec 17.
The aim of this study was to investigate the protective effect of L-carnitine (L-CAR) in tamoxifen (TAM)-induced toxicity and antitumor activity. Adult female rats were randomly divided into four groups. Group I was served as control, groups II and III were treated with TAM (10 mg/kg, periorally) and L-CAR (300 mg/kg, intraperitoneally), respectively, while group IV was treated with both compounds. The treatment continued daily for 28 days. Administration of TAM resulted in significant increase in serum lipid profiles, liver enzymes, and bilirubin level. TAM produced a significant increase in lipid peroxides (LPO) level and nonsignificant change in nitrogen oxide (NO(x)) level accompanied with significant decrease in superoxide dismutase (SOD) activity of hepatic and uterus tissues and significant decrease in glutathione (GSH) content of uterus tissue. Administration of L-CAR for 1 h prior to TAM treatment decreased serum lipids and liver enzymes significantly and significantly increased SOD activity in liver and uterus tissues compared with TAM-treated group. Furthermore, it restored LPO and GSH levels and increased NO(x) level in uterus tissue. DNA fragmentation and the apoptotic marker, caspase-3, were not detected in the liver of all treated groups. Histopathologically, alterations in the liver and uterus structures after TAM treatment, which was attenuated after L-CAR administration. The antitumor effect and survival of the combined treatment of Ehrlich ascites carcinoma (EAC)-bearing mice was less than each one alone. L-CAR interestingly increased survival rate of EAC-bearing mice more than TAM-treated group. In conclusion, L-CAR has beneficial effects regarding TAM toxicity; however, it interferes with its antitumor effect.
本研究旨在探讨左旋肉碱（L-CAR）对他莫昔芬（TAM）诱导的毒性及抗肿瘤活性的保护作用。成年雌性大鼠随机分为四组。第一组作为对照组，第二组和第三组分别经口给予TAM（10 mg/kg）和腹腔注射L-CAR（300 mg/kg），而第四组同时给予这两种化合物。治疗持续28天。给予TAM导致血清脂质谱、肝酶和胆红素水平显著升高。TAM使脂质过氧化物（LPO）水平显著升高，一氧化氮（NO(x)）水平无显著变化，同时肝组织和子宫组织的超氧化物歧化酶（SOD）活性显著降低，子宫组织的谷胱甘肽（GSH）含量显著降低。在TAM治疗前1小时给予L-CAR，与TAM治疗组相比，显著降低了血清脂质和肝酶水平，并显著提高了肝组织和子宫组织的SOD活性。此外，它恢复了子宫组织中LPO和GSH水平，并提高了NO(x)水平。在所有治疗组的肝脏中均未检测到DNA片段化和凋亡标志物caspase-3。组织病理学上，TAM治疗后肝脏和子宫结构发生改变，L-CAR给药后这种改变减弱。荷艾氏腹水癌（EAC）小鼠联合治疗的抗肿瘤效果和生存率低于单独使用每种药物。有趣的是，L-CAR使荷EAC小鼠的生存率比TAM治疗组更高。总之，L-CAR对TAM毒性具有有益作用；然而，它会干扰其抗肿瘤作用。
