Mohebbi Ehsan, Molavi Mehdi, Mohammadzadeh Mohammad, Hosseinzadeh Hossein, Amin Bahareh
Student Research Committee, Sabzevar University of Medical Sciences, Sabzevar, Iran.
Department of Internal Medicine, Sabzevar University of Medical Sciences, Mashhad, Iran.
Iran J Basic Med Sci. 2020 Jun;23(6):730-736. doi: 10.22038/ijbms.2020.39129.9287.
Ethanol withdrawal following chronic use, is an important challenge clinically. In this study, the effect of clavulanic acid was evaluated on the symptoms of ethanol withdrawal in rats.
Alcohol dependence was induced by the gavage of ethanol (10% v/v, 2 g/kg), twice daily for 10 days. Clavulanic acid (10, 20, 40, and 80 mg/kg) was administered concurrently with ethanol (sub-acute study), or a single dose after ethanol withdrawal (acute study). Six hours after the last dose of ethanol, anxiety was assessed by the elevated plus-maze (EPM). Seizure-like behavior was evaluated by a sub-convulsive dose of pentylenetetrazol (PTZ, 25 mg/kg/IP). Locomotor activity and motor coordination were measured by the open field and rotarod tests, respectively. Lipid peroxidation marker and antioxidant content were assessed through measuring malondialdehyde (MDA) and glutathione (GSH), respectively.
The number of entries and time spent on the open arms of EPM decreased during the withdrawal state. Motor coordination and locomotor activity were significantly decreased. In the sub-acute study, clavulanic acid 80 mg/kg increased time spent and the number of entries to the open arms of EPM, in withdrawn animals. Both motor incoordination and locomotor activity reduction were normalized by clavulanic acid (10, 20, 40 and 80 mg/kg). Withdrawal-induced PTZ kindling seizure was also suppressed by all of the doses. MDA increased, while GSH decreased after withdrawal. Clavulanic acid attenuated such changes.
Clavulanic acid could prevent the development of alcohol withdrawal-induced anxiety and seizure. Alcohol withdrawal causes oxidative stress which can be prevented by clavulanic acid.
长期使用乙醇后的戒断反应是临床上的一项重要挑战。在本研究中，评估了克拉维酸对大鼠乙醇戒断症状的影响。
通过每日两次灌胃给予乙醇（10% v/v，2 g/kg），持续10天诱导酒精依赖。克拉维酸（10、20、40和80 mg/kg）与乙醇同时给药（亚急性研究），或在乙醇戒断后给予单次剂量（急性研究）。在最后一剂乙醇给药6小时后，通过高架十字迷宫（EPM）评估焦虑。通过亚惊厥剂量的戊四氮（PTZ，25 mg/kg/腹腔注射）评估癫痫样行为。分别通过旷场试验和转棒试验测量运动活动和运动协调性。通过分别测量丙二醛（MDA）和谷胱甘肽（GSH）评估脂质过氧化标志物和抗氧化剂含量。
在戒断状态下，EPM开放臂的进入次数和停留时间减少。运动协调性和运动活动显著降低。在亚急性研究中，80 mg/kg的克拉维酸增加了戒断动物在EPM开放臂的停留时间和进入次数。克拉维酸（10、20、40和80 mg/kg）使运动不协调和运动活动减少均恢复正常。所有剂量的克拉维酸也抑制了戒断诱导的PTZ点燃性癫痫发作。戒断后MDA增加，而GSH减少。克拉维酸减轻了这些变化。
克拉维酸可预防酒精戒断引起的焦虑和癫痫发作。酒精戒断会导致氧化应激，而克拉维酸可预防这种应激。
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