Effects Of Ganoderma Lucidum Polysaccharides On Cisplatin-induced Pica And Brain Fos Expression In Mice

Chemical therapy is one of the first choice methods to cure cancer, but chemical medicament such as cisplatin always begets serious adverse drug reactions like nausea and vomit. Now, though 5-HT3 receptor antagonists for instance ondansetron,granisetron have good effect of stop vomiting in clinical application, their price is valuable, they have not very well effect to tardive vomit; people still have anxiousness to their safety. The application of Chinese medical science and traditional Chinese drug to relieve chemical therapy-induced nausea/vomiting has acquired great evolvement. But it has some scarcities, like effect is played relative slowly, weak specificity and so on; furthermore, most of this method is used in clinical observation, but few is in mechanism approach, so it is necessary to look for some medicament which has strong specificity,fine safety,good effective and approach. Some fungi polysaccharides have good effect on alleviating chemical therapy-induced symptoms such as nausea/vomiting,anepithymia; but its mechanism is not definitude in report. This research is to explore the influence of ganoderma lucidum polysaccharides on both kaolin intake of KM mice (a recognitive nausea/vomiting model) and Fos expression in their brain induced by cisplatin.Results:1. After injected intraperitoneally cisplatin(3mg/kg), the mice's intake of kaoline was increased; the most kaolin intake was on 1st day, then gradually decreased.2. The mice did not become pica, which were injected intraperitoneally ganoderma lucidum polysaccharides(150mg/kg), the intake of kaolin was basisly same to the Normal Saline group.3. After injected intraperitoneally granisetron(0.3mg/kg)and cisplatin, the intake of kaolin was less than cisplatin group,s on 1st day, the difference had significance(P<0.05); on 2nd-4th day, the two groups had no difference.4. The group injected intraperitoneally ganoderma lucidum polysaccharides and cisplatin, the intake of kaolin was less than cisplatin group,s on 1st-2nd day, difference had significance(P<0.05); on 3rd-4th day, no significant difference. But it still manifested trend that was less than cisplatin group.5. Compared to granisetron and cisplatin group, the intake of kaolin in ganoderma lucidum polysaccharides and cisplatin group was less in the 4 days, difference had significance(P<0.05)on 1st day, no significant difference on 2nd - 4th day.6. The Fos-like immunoreactive (FLI) neurons were extensive distribution in the brain areas including PVN,Arc,LPGi,AP,SolM,Mve,SpVe,LC,PBN and so on among the mice injected intraperitoneally cisplatin, and obvious more than the other 4 groups(injected Normal Saline group,injected ganoderma lucidum polysaccharides group,injected granisetron and cisplatin group,injected ganoderma lucidum polysaccharides and cisplatin group), had significant differences.7. The mice injected intraperitoneally cisplatin had the most FLI neurons in the brain areas. In injected intraperitoneally ganoderma lucidum polysaccharides and cisplatin group, expect SolM, others brain areas had significant differences(P<0.05)in FLI neurons. It explained that ganoderma lucidum polysaccharides could inhibit cisplatin-induced nausea/vomiting.8. Compared injected granisetron and cisplatin group with injected ganoderma lucidum polysaccharides and cisplatin group, the FLI neurons had no significant difference in PBN,AP,Arc,LPGi, FLI neurons of LC,SolM,PVN and MVe-SpVe in ganoderma lucidum polysaccharides and cisplatin group was more than granisetron and cisplatin group, had significant differences.Conclusions:1. In ethological experiment, mice were found obvious pica after injected intraperitoneally cisplatin. It could prove that the research can successfully repeat vomiting model in mice.2. After vomiting model was based, the pica was decreased which were injected intraperitoneally ganoderma lucidum polysaccharides and granisetron. Ganoderma lucidum polysaccharides had inhibitory effects for cisplatin-induced nausea/vomiting, the effect was better than granisetron which was traditional antiemetic. 3. FLI neurons were extensive distribution in the brain areas including PVN,Arc,LPGi,AP,SolM,MVe,SpVe,LC,PBN and so on, which suggested that c-fos expression may play an important role in nausea/vomiting and the sensation of stomach intestine.4. Mice were firstly injected intraperitoneally granisetron or ganoderma lucidum polysaccharides, then injected cisplatin, FLI neurons in the brain areas decreased obviously. Generally the trend basicly conform to the intake of kaolin; which indicated Fos expression reflexed the extent of nausea/vomiting, ganoderma lucidum polysaccharides had obvious inhibitory effects for cisplatin-induced nausea/vomiting.5. From Fos expression level in the brain, FLI neurons in AP,PBN,Arc and LPGi had no significant differences between the group of ganoderma lucidum polysaccharides and cisplatin and the group of granisetron and cisplatin, but showed increased trend. The extensive distribution of FLI neurons had significant differences with the group injected ganoderma lucidum polysaccharides and cisplatin in LC,SolM,PVN and MVe-SpVe. This phenomena suggested there was different mechanism on the inhibitory effects for cisplatin-induced nausea/vomiting with granisetron, such as anti-oxidative damage,immunomodulation to improve the organism intolerance of cisplatin induced toxicity.