Effect of protamine on the accumulation of gentamicin in opossum kidney epithelial cells

Abstract

Objectives The purpose of this study was to examine whether or not protamine, an arginine-rich basic protein mixture, inhibits the accumulation of gentamicin, a nephrotoxic drug, in cultured opossum kidney (OK) epithelial cells. Methods The effect of protamine from salmon on accumulation and binding of [3H]gentamicin was investigated in OK cells. Key findings Protamine inhibited the binding and accumulation of [3H]gentamicin in a concentration-dependent manner. The accumulation of [14C]inulin, a marker of fluid-phase endocytosis, was not affected by protamine at concentrations up to 1 mm. l-Arginine at concentrations up to 10 mm had no significant effect on the accumulation of [3H]gentamicin. On the other hand, preincubation with 100 μm protamine for 5 min decreased the accumulation of [3H]gentamicin to almost the same extent as coincubation with 100 μm protamine for 60 min. Conclusions Our results indicate that protamine decreases the accumulation of gentamicin in OK cells. These findings suggest that protamine or its derivatives might be useful in preventing the nephrotoxicity of aminoglycoside antibiotics including gentamicin. © 2012. Royal Pharmaceutical Society.