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 in the CCR during the 7 days after the injection, while platinum was not detected 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 ester dose-dependently lowered the platinum level. A dose of 5 mg/kg of aminoguanidine reduced the increase in the platinum level of the LPS-treated mouse, and platinum was no longer detected at doses of 20 mg/kg in the aminoguanidine-injected group. At doses of 500 mg/kg aminoguanidine, however, no effect was seen on the platinum level of the CCR induced by LPS. Regarding indomethacin, the injection of 5 mg/kg resulted in a decrease in the platinum content of the CCR, but not undetectable level. These results suggest that LPS increases the penetration of cisplatin into the mouse brain, and platinum may be accumulated in the CCR. Nitric oxide and prostaglandins contribute to the penetration of platinum into the cerebral cortex.
Minami
T
T
Department of Anatomy, Nara Medical University, Kashihara, Japan. minamita@naramed-u.ac.jp
Okazaki
J
J
Kawabata
A
A
Kuroda
R
R
Okazaki
Y
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002945:Cisplatin / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli; D006146:Guanidines / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010984:Platinum / Q000378:metabolism
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D006146:Guanidines; D008070:Lipopolysaccharides; D010984:Platinum; D002945:Cisplatin; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin