PREVENTION OF LITHIUM NEPHROTOXICITY IN A NOVEL ONE-HOUR MODEL IN RATS

It is well established that lithium can cause morphologically visible damage to the kidneys of humans and animals. Although the clinical sig nificance of its nephrotoxicity is debatable, it would be desirable to find a method to prevent lithium's effect on the kidneys. Toward this end, we have developed a novel method for producing nephrotoxicity th at will be useful for research on prevention. A single, large, toxic d ose of lithium chloride (LiCl) caused necrosis of the distal convolute d tubules, which was visible by light microscopy in 30 min, had fully developed in I h, and had disappeared by the next day. The lesions wer e seen after IP or IV injections of fasted rats of three different str ains. Equivalent doses of NaCl, KCI, MgCl2 and combinations thereof ha d no such effect, nor did they inhibit nephrotoxicity when incorporate d into the LiCl solution. However, relatively small doses of LiCl inje cted by any route 3 or 24 h beforehand prevented the nephrotoxicity. T he mechanism of prevention is not known, but it does not involve reduc tion of lithium levels in the kidneys.