Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Toxicol Mech Methods. 2006;16(6):331-7. doi: 10.1080/15376520600620067.
The effects of chlordiazepoxide, L-Arginine (nitric oxide precursor), L-NAME (nitric oxide synthesis inhibitor), and concurrent treatment of these drugs on concentration of salivary total protein, calcium, sodium, potassium concentrations, amylase activity, and flow rate in rats were studied. Total saliva was collected 2 hours postintraperitoneal administration of chlordiazepoxide (5 mg/kg), L-Arginine (250 mg/kg), and L-NAME (10 mg/kg) intraorally by polyethylene cannula from anaesthetized rats for 30 min using pilocarpine (6 mg/kg) as secretagogue. Chlordiazepoxide reduced flow rate to 43%, total protein concentration to 30%, calcium concentration to 33%, and amylase activity to 33% of control. Potassium and sodium levels were not affected by chlordiazepoxide. L-Arginine increased flow rate to 10%, total protein to 65%, and calcium to 17%, while L-NAME decreased flow rate to 9%, total protein to 55%, and calcium to 25%. Concurrent treatment of rats by chlordiazepoxide plus L-Arginine or L-NAME influenced chlordiazepoxide-induced alterations in saliva composition. The inhibitory effects of chlordiazepoxide on salivary flow rate, amylase activity, and concentrations of total protein and calcium were blocked by L-Arginine while potentiated by L-NAME coadministrations. It is concluded that benzodiazepines induce toxicity in salivary gland function by disturbing the homeostasis of inositol triphosphate and Ca homeostasis in the cells. Administration of L-Arginine prevents benzodiazepine-induced toxicity most probably through its vasoregulatory action and balancing intracellular Ca homeostasis.
研究了氯氮䓬（安定的一种）、L-精氨酸（一氧化氮前体）、L-NAME（一氧化氮合成抑制剂）以及这些药物联合应用对大鼠唾液总蛋白浓度、钙、钠、钾浓度、淀粉酶活性和流率的影响。用聚乙烯套管经口从麻醉大鼠收集 2 小时后腹腔内给予氯氮䓬（5mg/kg）、L-精氨酸（250mg/kg）和 L-NAME（10mg/kg）后的总唾液，用毛果芸香碱（6mg/kg）作为刺激物，收集 30 分钟。氯氮䓬将流率降低到对照的 43%，总蛋白浓度降低到 30%，钙浓度降低到 33%，淀粉酶活性降低到 33%。钾和钠水平不受氯氮䓬影响。L-精氨酸将流率增加到 10%，总蛋白增加到 65%，钙增加到 17%，而 L-NAME 将流率降低到 9%，总蛋白降低到 55%，钙降低到 25%。氯氮䓬加 L-精氨酸或 L-NAME 联合处理大鼠影响氯氮䓬诱导的唾液成分变化。L-精氨酸阻断氯氮䓬对唾液流率、淀粉酶活性以及总蛋白和钙浓度的抑制作用，而 L-NAME 联合处理则增强其作用。结论：苯二氮䓬类通过干扰细胞内三磷酸肌醇和 Ca 平衡干扰唾液腺功能的内稳态而导致毒性。L-精氨酸的给药可能通过其血管调节作用和平衡细胞内 Ca 平衡来预防苯二氮䓬类诱导的毒性。
