Mani Vasudevan, Rabbani Syed Imam, Shariq Ali, Amirthalingam Palanisamy, Arfeen Minhajul
Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia.
Department of Pathology, College of Medicine, Qassim University, Buraydah 51452, Saudi Arabia.
Pharmaceuticals (Basel). 2022 Dec 14;15(12):1563. doi: 10.3390/ph15121563.
Cancer chemotherapy is known to cause cognitive defects in patients. Our study investigated the effect of piracetam (PIRA; 200 or 400 mg/kg) against doxorubicin (DOX)-induced cognitive deficits in a rat model. The cognitive parameters were analyzed using elevated plus-maze, novel object recognition, and Y-maze tests. Acetylcholinesterase (AChE), neuroinflammatory mediators (cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), nuclear factor-κB (NF-κB), tumor necrosis factor-alpha (TNF-α)), apoptotic proteins (B-cell lymphoma-2 (Bcl-2), Bcl2 associated X protein (Bax), cysteine aspartate specific protease-3 (caspase-3)), oxidative parameters (malondialdehyde (MDA), catalase (CAT), and glutathione (GSH)) were also determined in the brain. PIRA administration offered significant protection against DOX-induced cognitive deficits in all maze tests and restored cholinergic functions via a significant reduction in AChE levels. Additionally, PIRA suppressed DOX-induced neuroinflammatory mediators (COX-2, PGE2, NF-κB, and TNF-α), pro-apoptotic proteins (Bax and caspase-3), and oxidative stress (MDA). Besides, it facilitated antioxidant (CAT and GSH) levels. Hence, our study highlighted that the neuroprotective activity of PIRA against DOX-induced cognitive deficits can be linked to reductions of AChE levels, neuro-inflammatory mediators, pro-apoptotic proteins, and oxidative stress.
众所周知，癌症化疗会导致患者出现认知缺陷。我们的研究调查了吡拉西坦（PIRA；200或400毫克/千克）对阿霉素（DOX）诱导的大鼠模型认知缺陷的影响。使用高架十字迷宫、新物体识别和Y迷宫测试分析认知参数。还测定了大脑中的乙酰胆碱酯酶（AChE）、神经炎症介质（环氧合酶-2（COX-2）、前列腺素E2（PGE2）、核因子-κB（NF-κB）、肿瘤坏死因子-α（TNF-α））、凋亡蛋白（B细胞淋巴瘤-2（Bcl-2）、Bcl2相关X蛋白（Bax）、半胱天冬酶-3（caspase-3））以及氧化参数（丙二醛（MDA）、过氧化氢酶（CAT）和谷胱甘肽（GSH））。在所有迷宫测试中，给予PIRA可显著保护大鼠免受DOX诱导的认知缺陷，并通过显著降低AChE水平恢复胆碱能功能。此外，PIRA可抑制DOX诱导的神经炎症介质（COX-2、PGE2、NF-κB和TNF-α）、促凋亡蛋白（Bax和caspase-3）以及氧化应激（MDA）。此外，它还提高了抗氧化剂（CAT和GSH）水平。因此，我们的研究强调，PIRA对DOX诱导的认知缺陷的神经保护活性可能与AChE水平、神经炎症介质、促凋亡蛋白和氧化应激的降低有关。
