Hafez Mona Hafez, El-Kazaz Sara Elsayed
Physiology Department, Faculty of Veterinary Medicine, Alexandria University, Alexandria, Egypt.
Animal Husbandry and Animal Wealth Development Department, Faculty of Veterinary Medicine, Alexandria University, Alexandria, Egypt.
J Adv Vet Anim Res. 2020 Apr 24;7(2):281-289. doi: 10.5455/javar.2020.g419. eCollection 2020 Jun.
The purpose of this work was to investigate the effect of phosphodiesterase type 5 (PDE-5) inhibitor sildenafil citrate (SC) on the level of brain hippocampal neurophysiological parameters (inhibitory and excitatory neurotransmitters), oxidant/antioxidant status, minerals, and anxiety-like behavior using albino male rats.
A total of 24 albino male rats were allocated to three separate groups (each one had eight rats): control and SC 5 and 10 mg/kg treatments via i.p. infusion every 3 days for 12 injections. For the behavior of anxiety evaluation, the elevated plus maze test was conducted 1 day after the last treatment, and then all the rats were killed. For serum separation, the blood samples were taken, and hippocampus was dissected from the brain and stored frozen until analysis.
Both doses of sildenafil significantly improved brain hippocampal neurotransmitter [norepinephrine, serotonin (5-hydroxytryptamine), and gamma-aminobutyric acid] values accompanied by a decreased dopamine level. Interestingly, the SC higher given dose (10 mg/kg) increased the malondialdehyde level with the reduction of the antioxidant parameters [reduced glutathione (GSH) level, catalase (CAT), and superoxide dismutase (SOD) activities] although the lower dose of SC did not cause oxidative stress. Serum and brain hippocampal K, Cu, and Se concentrations were also increased with SC treatments. Moreover, the test of elevated plus maze revealed an anxiolytic impact of sildenafil.
It was concluded that SC improved the parameters of some hippocampal neurotransmitters and minerals accompanied by anxiolytic impact with the test of elevated plus maze, with a state of oxidative stress revealed with the higher dose of SC which was not recorded with the lower dose.
本研究旨在使用白化雄性大鼠，探讨5型磷酸二酯酶（PDE - 5）抑制剂枸橼酸西地那非（SC）对脑海马神经生理参数（抑制性和兴奋性神经递质）水平、氧化/抗氧化状态、矿物质及焦虑样行为的影响。
将24只白化雄性大鼠分为三个独立组（每组8只）：对照组以及分别给予5 mg/kg和10 mg/kg SC处理组，每3天腹腔注射一次，共注射12次。在最后一次处理后1天进行高架十字迷宫试验以评估焦虑行为，然后处死所有大鼠。采集血样用于血清分离，从脑中分离出海马并冷冻保存直至分析。
两种剂量的西地那非均显著改善脑海马神经递质[去甲肾上腺素、血清素（5 - 羟色胺）和γ - 氨基丁酸]值，同时多巴胺水平降低。有趣的是，较高剂量（10 mg/kg）的SC增加了丙二醛水平，同时抗氧化参数[还原型谷胱甘肽（GSH）水平、过氧化氢酶（CAT）和超氧化物歧化酶（SOD）活性]降低，而较低剂量的SC未引起氧化应激。SC处理还使血清和脑海马中的钾、铜和硒浓度升高。此外，高架十字迷宫试验显示西地那非具有抗焦虑作用。
得出结论，SC改善了一些海马神经递质和矿物质参数，并在高架十字迷宫试验中具有抗焦虑作用，较高剂量的SC显示出氧化应激状态，而较低剂量未出现此情况。
