Penetration of cisplatin into mouse brain by lipopolysaccharide

We investigated the penetration of cisplatin into the mouse cerebral cortex -rich region (CCR) induced by lipopolysaccharide (LPS). With the injection of cisplatin into mice 3 h after the LPS treatment, platinum was detected i n the CCR during the 7 days after the injection, while platinum was not det ected in the CCR of cisplatin-injected mice without LPS pretreatment and of mice simultaneous treated with cisplatin and LPS. The N-G-nitro-L-arginine methyl eater dose-dependently lowered the platinum level. A dose of 5 mg/k g of aminoguanidine reduced the increase in the platinum level of the LPS-t reated mouse, and platinum was no longer detected at doses of 20 mg/kg in t he aminoguanidine-injected group. At doses of 500 mg/kg aminoguanidine, how ever, no effect was seen on the platinum level of the CCR induced by LPS, R egarding indomethacin, the injection of 5 mg/kg resulted in a decrease in t he platinum content of the CCR, but not undetectable level. These results s uggest that LPS increases the penetration of cisplatin into the mouse brain , and platinum may be accumulated in the CCR. Nitric oxide and prostaglandi ns contribute to the penetration of platinum into the cerebral cortex. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.