Lithium is eliminated from the body primarily in the urine. Amelioration of the lithium clearance by GR205171 is consistent with the improvements in creatinine clearance and histological damage produced by the NK1 receptor antagonist. As previously shown in ferrets, treatment with GR203040, a selective NK 1 receptor antagonist, reduced the renal damage induced by cisplatin in rats. The improvements in histological findings are in agreement with the amelioration in renal function, and support the role for sP and NK 1 receptors in the nephrotoxicity associated with cisplatin treatment. Our findings suggest that at least part of the renal damage and renal dysfunction produced by cisplatin in rats may be the consequence of inflammatory changes associated with or mediated by sP acting on NK 1 receptors.
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