Cyclosporin A enhanced protection of nimodipine against brain damage induced by hypoxia-ischemia in mice and rats.
OBJECTIVE
To study whether P-glycoprotein (P-gp) inhibitor cyclosporin A (CsA) enhanced the protection of nimodipine (NMD) against brain damage.


METHODS
(1) After mice were given ip NMD alone or co-administration of CsA, survival time of mice were recorded following decapitation and ip injection of NaNO2, respectively. (2) After rats were given ip NMD alone or co-administration of CsA, 20 min forebrain ischemia induced by the technique of two-carotid occlusion plus hypovolemic hypotension. Following reperfusion of 1 h, the content of malondialdehyde (MDA), lactic acid (LA) and activity of lactic dehydrogenase (LDH) in cortex tissue were measured. (3) NMD level in brain was also determined after ip injection of NMD 2 mg/kg alone and co-administration of CsA, respectively.


RESULTS
NMD showed potent pharmacological activity in the three models. The survival time of mice by decapitation and ip NaNO2 were significantly (P <0.05) prolonged after co-administration of CsA. In rat forebrain ischemia/reperfusion, levels of MDA, LA, and LDH by co-administration of CsA were greatly modified, compared with those of NMD alone group. The level of NMD in rat brain was increased markedly after co-administration of CsA.


CONCLUSIONS
P-gp inhibitor CsA may enhance the protection of NMD against brain damage.
Liu
Xiao-Dong
XD
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China. xdliu@jlonline.com
Pan
Guo-Yu
GY
Xie
Lin
L
Hou
Yuan-Yuan
YY
Lan
Wen
W
Su
Qing
Q
Liu
Guo-Qing
GQ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000517:prevention & control; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009553:Nimodipine / Q000494:pharmacology* / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002121:Calcium Channel Blockers; D018696:Neuroprotective Agents; D008315:Malondialdehyde; D009553:Nimodipine; D016572:Cyclosporine; D007770:L-Lactate Dehydrogenase