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评估左乙拉西坦对雄性 Wistar 大鼠唾液腺生化、功能和氧化还原参数的毒性作用。

Assessment of the toxic effects of levetiracetam on biochemical, functional, and redox parameters of salivary glands in male Wistar rats.

机构信息

Departmento de Ciências Básicas, Universidade Estadual Paulista (Unesp), Faculdade de Odontologia, Araçatuba, São Paulo, Brazil; Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas, SBFis, Universidade Estadual Paulista (Unesp), Faculdade de Odontologia, Araçatuba, São Paulo, Brazil.

Departmento de Ciências Básicas, Universidade Estadual Paulista (Unesp), Faculdade de Odontologia, Araçatuba, São Paulo, Brazil.

出版信息

Toxicology. 2023 Sep;496:153615. doi: 10.1016/j.tox.2023.153615. Epub 2023 Aug 11.

Abstract

Levetiracetam (LEV) is an anticonvulsant for epilepsy. The toxic effects of this medication in tissues have been associated with redox state imbalance, which can lead to salivary gland dysfunction. Therefore, the current work investigated the effects of LEV on the biochemical, functional, and redox parameters of the parotid and submandibular glands in rats. For this, male Wistar rats (Rattus norvegicus albinus) were randomly divided into 3 groups (n = 10/group): Control (0.9% saline solution), LEV100 (100 mg/kg), and LEV300 (300 mg/kg). After 21 consecutive days of intragastric gavage treatments, pilocarpine stimulated saliva secretion was collected for salivary biochemical analysis. The extracted salivary glands were utilized for histomorphometry and redox state analyses. Our results showed that LEV300 increased plasma hepatotoxicity markers and reduced salivary amylase activity and the acinar surface area of the parotid gland. Total oxidant capacity and oxidative damage to lipids and proteins were higher in the parotid gland, while total antioxidant capacity and uric acid levels were reduced in the submandibular gland of the LEV100 group compared to Control. On the other hand, total oxidant capacity, oxidative damage to lipids and proteins, total antioxidant capacity, and uric acid levels were lower in both salivary glands of the LEV300 group compared to Control. Superoxide dismutase and glutathione peroxidase activities were lower in the salivary glands of treated animals compared to Control. In conclusion our data suggest that treatment with LEV represents a potentially toxic agent, that contributes to drug-induced salivary gland dysfunction.

摘要

左乙拉西坦(LEV)是一种抗癫痫药物。该药物在组织中的毒性作用与氧化还原状态失衡有关,这可能导致唾液腺功能障碍。因此,目前的工作研究了 LEV 对大鼠腮腺和颌下腺生化、功能和氧化还原参数的影响。为此,将雄性 Wistar 大鼠(白化 Rattus norvegicus albinus)随机分为 3 组(每组 n=10):对照组(0.9%生理盐水)、LEV100 组(100mg/kg)和 LEV300 组(300mg/kg)。连续灌胃 21 天后,收集匹罗卡品刺激的唾液进行唾液生化分析。提取的唾液腺用于组织形态计量学和氧化还原状态分析。结果显示,LEV300 增加了血浆肝毒性标志物,降低了唾液淀粉酶活性和腮腺的腺泡表面积。与对照组相比,LEV100 组腮腺的总氧化剂能力和脂质及蛋白质的氧化损伤增加,而颌下腺的总抗氧化能力和尿酸水平降低。另一方面,与对照组相比,LEV300 组两种唾液腺的总氧化剂能力、脂质和蛋白质的氧化损伤、总抗氧化能力和尿酸水平均降低。与对照组相比,处理动物的唾液腺中超氧化物歧化酶和谷胱甘肽过氧化物酶的活性较低。综上所述,我们的数据表明,LEV 的治疗可能是一种潜在的有毒物质,会导致药物引起的唾液腺功能障碍。

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