Effect of Sodium Salicylate on Calcium Currents and Exocytosis in Cochlear Inner Hair Cells: Implications for Tinnitus Generation / 神经科学通报·英文版

Sodium salicylate is an anti-inflammatory medication with a side-effect of tinnitus. Here, we used mouse cochlear cultures to explore the effects of salicylate treatment on cochlear inner hair cells (IHCs). We found that IHCs showed significant damage after exposure to a high concentration of salicylate. Whole-cell patch clamp recordings showed that 1-5 mmol/L salicylate did not affect the exocytosis of IHCs, indicating that IHCs are not involved in tinnitus generation by enhancing their neuronal input. Instead, salicylate induced a larger peak amplitude, a more negative half-activation voltage, and a steeper slope factor of Ca2+ current. Using noise analysis of Ca2+ tail currents and qRT-PCR, we further found that salicylate increased the number of Ca2+ channels along with CaV1.3 expression. All these changes could act synergistically to enhance the Ca2+ influx into IHCs. Inhibition of intracellular Ca2+ overload significantly attenuated IHC death after 10 mmol/L salicylate treatment. These results implicate a cellular mechanism for tinnitus generation in the peripheral auditory system.

enhancing effect of sodium glycocholate and sodium salicylate on rats gastro-intestinal permeability to insulin

There have been numerous efforts to formulate insulin into an oral dosage form. The major problems involved with the oral administration of insulin are acidic and enzymatic decomposition by the gastric medium, and poor absorption in the small intestine due to its macromolecular structure. This study attempted to test the enhancing ability of two absorption enhancers, sodium glycocholate [Na-GC] and sodium salicylate [Na-Sal], in different parts of rat's gastrointestinal tract. The amount of insulin in each formulation was 0.6 iu/kg body weight. The concentration of enhancers [Na-Sal or Na-GC] in each formulation was 10 micro g/ml. Formulations made of insulin and enhancers were prepared and injected directly to stomach, duodenum, jejunum and ileum of anesthetized rats through an abdominal incision. Blood samples were taken at 45 and 60 min intervals. The glucose concentration was determined by the o-toluidine method. Injections [IP] of insulin and normal saline were positive and negative controls, respectively. The blood glucose concentrations showed a significant decrease [p<0.05] due to the injection of insulin into duodenum, while the effect noted in jejunum was insignificant [p>0.05]. Also, there was no anti-hyperglycemic effect accompanied by formulations administered into the stomach and ileum. It could be concluded that insulin, if formulated in a protected form to prevent acidic and enzymatic decomposition, in combination with such enhancers may overcome hyperglycemia due to insulin deficiency