Effects of nimodipine and fructose-1,6-diphosphate on cerebral damage in carbon monoxide poisoning mice.
OBJECTIVE
To study the dose- and time-dependent protective effects and the synergistic effects of nimodipine (NMDP) and fructose-1,6-diphosphate (FDP) against cerebral damage induced by acute carbon monoxide (CO) poisoning in mice.


METHODS
Male mice were exposed to CO 170 mL/kg, i.p. After CO intraperitonealy exposure, mortality of mice, change in memory function estimated by passive avoidance test, the pathomorphologic observation of brain tissue slices, as well as changes of activities of monoamine oxidase (MAO)-B and Ca(2+)-Mg(2+)-ATPase in cerebral tissue were studied. In dose-dependent protective effect study, NMDP (10.6, 5.3, 2.7 mg/kg) and FDP (2.6, 1.3, 0.67 g/kg) was injected ip, respectively 15 min after CO exposure. To study the time-effect relationship of drugs, NMDP (5.3 mg/kg) and FDP (1.3 g/kg) were administered ip respectively 15 minutes, 45 minutes and 120 minutes after CO exposure. The combination of NMDP (2.7 mg/kg) and FDP (0.67 g/kg) was administered ip15 minutes, 45 min and 120 minutes after CO exposure to study the synergism of the two drugs.


RESULTS
Either NMDP (10.6, 5.3 mg/kg) or FDP (2.6, 1.3 g/kg) administered ip within 15 minutes after CO exposure significantly decreased the impairment of memory function and mortality rate induced by CO, inhibited the decrease of Ca(2+)-Mg(2+)-ATPase activity, blunted the rising of MAO-B activity and prevented the delayed hippocampal neuronal death in poisoning mice. To our surprise, the combined use of NMDP (2.7 mg/kg) and FDP (0.67 g/kg) within 15 minutes after CO exposure had similar effects to that in NMDP (10.6, 5.3 mg/kg) and FDP (2.6, 1.3 g/kg).


CONCLUSIONS
These results suggest that the impairment of CO on brain can be attenuated if NMDP or FDP are administered sufficiently and quickly as soon as possible after CO exposure and there exists a synergism of FDP and NMDP against CO poisoning damage.
Yang
Junqing
J
Department of Pharmacology, Chongqing Medical University, Chongqing 400016, China. QQQJY@shou.com
Zhao
Xiaohui
X
Zhou
Qixin
Q
Jiang
Qingsong
Q
D000818:Animals; D001925:Brain Damage, Chronic / Q000517:prevention & control*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002249:Carbon Monoxide Poisoning / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005635:Fructosediphosphates / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009553:Nimodipine / Q000627:therapeutic use*; D013997:Time Factors
D002121:Calcium Channel Blockers; D005635:Fructosediphosphates; D018696:Neuroprotective Agents; D009553:Nimodipine; C029063:fructose-1,6-diphosphate