Relevance Of The Ameliorating Of Gastric Emptying By Curcumin To Nitric Oxide In Cisplatin Treated Mice

Objective The content of nitric oxide in gastric tissue and gastric emptying,and the total nitric oxide synthaseactivity,inducible nitric oxide synthase activity was detected,to investigate the effect of curcumin by intragastric administrated for different days on the dysfunction of gastric emptying in mice induced by cisplatin.Furtherly,to explore whether the effect of curcumin worked through NO pathway on ameliorating the dysfunction of gastric emptying in mice induced by cisplatin.Methods Adult male Kunming mice were randomly divided into 9 groups: control,cisplatin,curcumin,cisplatin+curcumin 1 day,5 days,10 days,15 days,20 days and 30 days.There were eight mice in each group.The mice were disposed of curcumin(200mg/kg/d)by intragstraic administration,for the number of days needed individually.The other groups were administrated with menstrum solution.Intraperitoneal injection of cisplatin(2mg/kg/d)was started from 5t h day before the execution.The other groups were injected with menstrum solution.Body weight changes were measured before and after the injection of cisplatin.Mice were fasted for 24 hours after last administration and the gastric emptying rate were detected in each group.Then the mice were dislocated to death,and the stomach tissues of mice were cut out.The content of NO and the activity of NOS in stomach were detected.All data are presented as means ± SD.To compare data among groups of animals,one-way analysis of variance(one-way ANOVA),Q test,variance analysis and factorial analysis by SPSS 17.0 were employed.Differences were considered statistically significant at P < 0.05.Results Compared with control group,the body weight of mice in cisplatin group were reduced significantly after DDP injection(P<0.01),and the gastric emptying rate of mice were decreased obviously(P<0.01).The activity of TNOS(P<0.01)and i NOS(P<0.01)of mice stomach were significantly increased.The content of NO(P<0.01)in mice stomach were obviously increased.Compared with DDP group,curcumin group for 5 days has no significant changes in gastric emptying rate(P>0.05),while in curcumin group for 10 days,15 days,20 days and 30 days,the gastric emptying rates were significantly improved compared with DDP group(P<0.05 or P<0.01),and the body weights of mice were also recovered(P<0.05 or P<0.01)in these four groups compared with DDP group individually.In DDP+curcumin for 30 d group,the activity of TNOS and i NOS of gastric tissue of mice was significantly decreasedcompared with DDP group(P<0.01).At the same time,the content of NO was also decreased significantly(P<0.0 1).No significant changes of NO content and NOS activity were observed in DDP+curcumin for 5-20 days groups(P>0.05).There was no significant effect on normal mice in single curcumin group(P>0.05).Conclusions Cisplatin can induce the dysfunction of gastric emptying in mice,increase the content of NO and the activity of NOS in gastric tiss ue,which may be one of the mechanisms leading to the delayed gastric emptying.Pretreatment of curcumin by intragstraic administration for 30 days can inhibit the changes of NOS and NO induced by DDP in gastric tissue of mice,which may be one of the mechanisms of curcumin improving the delayed gastric emptying induced by DDP.Pretreatment of Curcumin for 10-20 days can also improve the delayed gastric emptying induced by DDP,but does not affect the production of NO of gastric tissue in mice,suggesting t here is other mechanism needs to be explored.Intragstraic administration of curcumin alone does not affect gastric emptying and NO content in normal mice,indicating that curcumin plays a role in intervention only when NO production was increased.