Al-Amin Md Mamun, Hasan S M Nageeb, Alam Tanzir, Hasan Ahmed Tasdid, Hossain Imran, Didar Rohini Rowshan, Alam Md Ashraful, Rahman Md Mahbubur
Department of Pharmaceutical Sciences, North South University, Bashundhara, Dhaka 1229, Bangladesh.
Department of Pharmaceutical Sciences, North South University, Bashundhara, Dhaka 1229, Bangladesh.
Eur J Pharmacol. 2014 Dec 15;745:84-90. doi: 10.1016/j.ejphar.2014.10.026. Epub 2014 Oct 23.
Tadalafil, a type-5 phosphodiesterase enzyme inhibitor with long half-life used to treat erectile dysfunction. Recently it has been reported that tadalafil improves cognitive function. Here, we aimed to investigate the age dependent effects of tadalafil on memory, locomotor, behavior, and oxidative stress in the hippocampus. Tadalafil was orally administered everyday (5 mg/kg) to young (2 months) and old (16 months) healthy mice for 4 weeks. Control mice from each group received equal volume of 0.9% normal saline for the same duration. Memory and locomotor activity were tested using radial arm maze and open field test respectively. The level of malondialdehyde (MDA), nitric oxide (NO), and advanced protein oxidation product (APOP) was analyzed and catalase activity was determined from the isolated hippocampus. Treatment with tadalafil in aged mice improves working memory than the corresponding tadalafil treated young mice in radial arm maze test. Tadalafil treated mice traveled less distance in the center and the mean speed of tadalafil treated aged mice was significantly lower than the tadalafil treated young mice in open field test. Tadalafil treatment elicited a decrease of MDA level in the hippocampus of aged mice than that of young mice. APOP level was decreased only in aged mice treated with tadalafil. Treatment with tadalafil decreased NO and increased catalase activity in both young and aged mice. On the basis of previous and our findings, we conclude that tadalafil treatment reduces oxidative stress while increased cGMP level in the hippocampus might be responsible for memory enhancement.
他达拉非是一种用于治疗勃起功能障碍的5型磷酸二酯酶抑制剂，半衰期长。最近有报道称他达拉非可改善认知功能。在此，我们旨在研究他达拉非对年轻（2个月）和老年（16个月）健康小鼠海马体中记忆、运动、行为及氧化应激的年龄依赖性影响。每天给年轻和老年健康小鼠口服他达拉非（5毫克/千克），持续4周。每组的对照小鼠在相同时间段内接受等量的0.9%生理盐水。分别使用放射状臂迷宫和旷场试验测试记忆和运动活动。分析丙二醛（MDA）、一氧化氮（NO）和晚期蛋白质氧化产物（APOP）的水平，并从分离的海马体中测定过氧化氢酶活性。在放射状臂迷宫试验中，老年小鼠接受他达拉非治疗后的工作记忆比相应接受他达拉非治疗的年轻小鼠更好。在旷场试验中，接受他达拉非治疗的小鼠在中央区域移动的距离较短，且接受他达拉非治疗的老年小鼠的平均速度显著低于接受他达拉非治疗的年轻小鼠。与年轻小鼠相比，他达拉非治疗使老年小鼠海马体中的MDA水平降低。仅在接受他达拉非治疗的老年小鼠中，APOP水平降低。他达拉非治疗使年轻和老年小鼠的NO水平降低，过氧化氢酶活性增加。基于先前的研究结果和我们的发现，我们得出结论，他达拉非治疗可降低氧化应激，而海马体中cGMP水平的升高可能是记忆增强的原因。
