Prevention by L-arginine/nitric oxide of chlordiazepoxide-induced toxic reactions in the rat salivary gland

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.