Alharbi Ibrahim, Alharbi Hindi, Almogbel Yasser, Alalwan Abdullah, Alhowail Ahmad
Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia.
Department of Pharmacy Practice, College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia.
Brain Sci. 2020 Mar 7;10(3):152. doi: 10.3390/brainsci10030152.
Doxorubicin (DOX) is widely used to treat many types of cancer; however, it is associated with chemotherapy-related complications such as cognitive dysfunction, known as chemobrain. Chemobrain affects up to 75% of cancer survivors, and there are currently no available therapeutic options. This study aims to examine whether metformin (MET) can protect against the neurotoxicity caused by DOX treatment. Forty male rats were divided into four groups (10 rats/group): control, DOX, DOX + MET, and MET. Rats treated with DOX received five doses of 4 mg/kg DOX weekly (cumulative dose: 20 mg/kg). For the DOX-MET and MET groups, MET (3 mg/mL) was dissolved in drinking water. Behavioral and glucose tests were performed one day after treatment was completed. We found DOX (4 mg/kg/week, 5 weeks) caused learning and memory impairment in the Y-maze, novel object recognition, and elevated plus maze behavioral tests. MET did not rescue these DOX-induced memory impairments. Neither DOX nor MET nor MET + DOX altered glucose levels following the treatment. In summary, DOX treatment is associated with memory impairment in rats, but MET does not rescue this cognitive dysfunction.
阿霉素（DOX）被广泛用于治疗多种癌症；然而，它与化疗相关的并发症有关，如认知功能障碍，即所谓的化疗脑。化疗脑影响多达75%的癌症幸存者，目前尚无有效的治疗选择。本研究旨在探讨二甲双胍（MET）是否能预防DOX治疗引起的神经毒性。40只雄性大鼠分为四组（每组10只）：对照组、DOX组、DOX + MET组和MET组。接受DOX治疗的大鼠每周接受5次剂量为4 mg/kg的DOX（累积剂量：20 mg/kg）。对于DOX-MET组和MET组，将MET（3 mg/mL）溶解于饮用水中。在治疗完成后一天进行行为和葡萄糖测试。我们发现DOX（4 mg/kg/周，共5周）在Y迷宫、新物体识别和高架十字迷宫行为测试中导致学习和记忆障碍。MET未能挽救这些由DOX诱导的记忆障碍。治疗后，DOX、MET以及MET + DOX均未改变葡萄糖水平。总之，DOX治疗与大鼠的记忆障碍有关，但MET不能挽救这种认知功能障碍。
