Inhibition of gentamicin-induced nephrotoxicity by lithium in rat

Daily intraperitoneal injection of gentamicin in doses of 2, 4 and 10 mg/kg/day for 5 consecutive days produced proximal tubular necrosis in male albino rats as assessed by ultrastructural findings from electron microscopic observations. With respect to nephrotoxicity, aminoglycoside antibiotics (AGs) have been shown to concentrate in the lysosomes of kidney proximal tubular cells to inhibit the activities of phospholipases A and C, including a phospholipidosis, characterized by the formation of myeloid bodies. It has been suggested that the nephrotoxicity of AGs is related to the extent of this phospholipidosis. The concurrent therapy of lithium in doses of 5 and 10 mEq/kg/day, administered subcutaneously, 24 hours prior to gentamicin administration for the same period, proved effective in reducing the gentamicin-induced phospholipidosis in kidney as judged by reduction in lysosomal myeloid bodies to an amount of 26-45 percent. It is well known that lithium interferes with phosphatidylinositol turnover and reduces the cellular availability of myoinositol which is needed for the resynthesis of membrane polyphosphoinositides. Thus, the inhibitory effect of lithium on gentamicin-induced nephrotoxicity may be due to interference of lithium with phosphoinositide cycle.