Koriem Khaled M M, El-Qady Sara W B
Medical Physiology Department, Medical Research and Clinical Studies Institute, National Research Centre, Dokki, Giza, Egypt.
Pathology Department, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
Neurotoxicology. 2023 Dec;99:70-81. doi: 10.1016/j.neuro.2023.09.007. Epub 2023 Sep 18.
One of the most powerful stimulants of the central nervous system is methamphetamine (METH). Linalool has a neuroprotective effect against ischemia injury by reducing oxidative stress and apoptosis. The present study investigated whether linalool can reverse the hypothalamus neurotoxicity and proteome disturbance in METH-treated rats.
A total of 36 male albino rats were split into two equal groups (normal and METH-treated). Three equal subgroups of normal rats were created; Control, Linalool (25 mg/kg), and Linalool (50 mg/kg); Normal rats were given daily oral doses of 1 ml of distilled water, 25 mg/kg linalool, and 50 mg/kg of linalool, respectively. METH groups were divided into 3 equal subgroups; METH-treated rats, Linalool (25 mg/kg)+METH-treated, and Linalool (50 mg/kg)+METH-treated subgroups; METH-treated rats received daily and oral doses of 1 ml distilled water, 25 mg/kg linalool, and 50 mg/kg of linalool, respectively.
According to the data obtained, METH caused a decrease of the sucrose preference test, travel distance test, and center square entries test, superoxide dismutase, glutathione peroxidase, catalase, NADPH oxidase, interleukin-10 but a rise in the center square duration test, tail suspension test, and forced swimming test, malondialdehyde, conjugated dienes, oxidative index, serotonin, dopamine, norepinephrine, γ-aminobutyric acid, tumour necrosis factor-α, interleukin-1β, interleukin-6 levels. When compared to the control group, rats treated with METH had lower sodium/potassium ATPase activity and missing of prothrombin, fibrinogen, and ceruloplasmin protein bands in the hypothalamus. In METH-treated rats, daily and oral co-administration with linalool brought all these parameters back to values that were close to control.
According to obtained data, linalool could protect the hypothalamus against METH-induced neurotoxicity and proteome disturbance probably by modifying oxidative stress, neurotransmitters, inflammation, sodium/potassium-ATPase activity, proteome disturbance, and tissue histology in METH-treated rats where higher dose of linalool was more efficient than lower dose.
甲基苯丙胺（METH）是中枢神经系统最强大的兴奋剂之一。芳樟醇通过降低氧化应激和细胞凋亡对缺血性损伤具有神经保护作用。本研究调查了芳樟醇是否能逆转METH处理大鼠的下丘脑神经毒性和蛋白质组紊乱。
将36只雄性白化大鼠分成两个相等的组（正常组和METH处理组）。正常大鼠再分为三个相等的亚组：对照组、芳樟醇（25mg/kg）组和芳樟醇（50mg/kg）组；正常大鼠分别每日口服1ml蒸馏水、25mg/kg芳樟醇和50mg/kg芳樟醇。METH组分为3个相等的亚组：METH处理大鼠组、芳樟醇（25mg/kg）+METH处理组和芳樟醇（50mg/kg）+METH处理组；METH处理大鼠分别每日口服1ml蒸馏水、25mg/kg芳樟醇和50mg/kg芳樟醇。
根据所得数据，METH导致蔗糖偏好试验、行进距离试验和中央方格进入试验、超氧化物歧化酶、谷胱甘肽过氧化物酶、过氧化氢酶、NADPH氧化酶、白细胞介素-10降低，但中央方格持续时间试验、尾悬挂试验和强迫游泳试验、丙二醛、共轭二烯、氧化指数、5-羟色胺、多巴胺、去甲肾上腺素、γ-氨基丁酸、肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6水平升高。与对照组相比，METH处理的大鼠下丘脑钠/钾ATP酶活性较低，且缺乏凝血酶原、纤维蛋白原和铜蓝蛋白蛋白条带。在METH处理的大鼠中，每日口服芳樟醇可使所有这些参数恢复到接近对照的值。
根据所得数据，芳樟醇可能通过调节氧化应激、神经递质、炎症、钠/钾-ATP酶活性、蛋白质组紊乱和组织组织学，保护下丘脑免受METH诱导的神经毒性和蛋白质组紊乱，其中较高剂量的芳樟醇比较低剂量更有效。
