Metabolism Of Baicalin And Effects On Residue And Elimination Of Norfloxacin In Fenneropenaeus Chinensis

Medicine plays an important role in disease control of aquatic animals, the application of antibiotics can control bacterial diseases in aquaculture, however, it also can bring many problems, for example, medicial resistance and residue, which cause people's attention. Because of their low toxicity and residue, Chinese herbal medicine has gradually applied to aquaculture, it is very important to develop pollution-free fishery medicines. While Chinese herbal medicine also has some deficiencies in practical application, for example, lacking of basic research, producing results slowly, using a large amount of medcines and so on. In view of this, people began to join together of Chinese herbal medicine and antibiotics. however, combined medicines lack effective guidance. Therefore, this research selected Fenneropenaeus chinensis as experimental animals, studied effects of baicalin on resuide and elimination of norfloxacin in Fenneropenaeus chinensis. The study consists of two parts:The first part:Metabolism and elimination of baicalin and effects on CYP450s and GST in Fenneropenaeus chinensisThe shrimps Fenneropenaeus chinensis were treated with baicalin at dose of 100mg/kg weight body per day for seven days at (24±1)℃, different tissues of the shrimp were collected and analyzed by HPLC, HPLC method was established to detect the residue and elimination of the baicalin from shrimps. Activity of APND,ECOD,GST was measured in hepatopancreas and gills of shrimps by UV spectrophotometry and Fluorospectrophotometry, effects on APND,ECOD,GST activity in hepatopancreas and gills were studied following multi-oral baicalin. On this basis, established PKPD model of baicalin in the shrimps taking metabolism changes as an indicator of pharmacokinetics and drug metabolism enzyme activity as an indicator of pharmacodynamic. The results showed that the established HPLC method was efficient because the baicalin and impurities could be highly separated. In four concentration level, averange recovery rate of baicalin was between 80.57%-96.25%, within-day precision was between 3.26%-5.85%, between-day precision was between 3.88%-5.73% from four tissues. Compared with other administrations, baicalin was absorbed slower following seven days of multi-administration, the Tmax of blood,hepatopancreas,muscle and gills were 6h,3h,6h,3h, respectively, the concentration decreased in the following order:hepatopancreas>gills>blood>muscle, t1/2βin hepatopancreas,gills,blood and muscle was 29.62h,27.50h,25.20h,23.73h respectively. The baicalin was less residual in shrimps, it had dropped below detection limit in the fifth day in muscle and blood while in the seventh day in hepatopancreas and gills. The results of eneyme activity showed that three enzyme activity was differently induced after multi-oral baicalin at dose of 1 OOmg/kg weight body per day for seven days at (24±1)℃. APND activity of hepatopancreas and gills rose to highest at 3h after final feeding; ECOD activity of hepatopancreas and gills rose to highest at 1h after final feeding; GST activity of hepatopancreas and gills rose to highest at 6h and 12h respectively. The established PKPD model met with cubic equation, the regression coefficient is high, it had a direct relationship between baicalin content and enzyme activity. The study provided application references for medicine containing baicalin, it reminded us to use medicines reasonably considering inductive effect on CYP450 and GST of baicalin in clinical.The second part:Effects of baicalin on norfloxacin residue and elimination in Fenneropenaeus chinensisThe shrimps were divided into three parts:control group, single treatment group, combined treatment group:control group were fed without medicines, single treatment group were fed with norfloxacin five days, combined treatment group were fed with norfloxacin five days, then fed with baicalin ten days. Norfloxacin was analyzed by HPLC in single treatment group and combined treatment group, activity of APND,ECOD,GST was measured in hepatopancreas of Fenneropenaeus chinensis by UV spectrophotometry and Fluorospectrophotometry. The results showed that:from the respects of metablism and elimination, we can see norfloxacin metabolism rate accelerated, elimination rate accelerated and residue reduced in combined treatment group compared with single treatment group. In addition, the t1/2βwas shortened obviously in combined treatment group, the theory withdrawal period of combined treatment group reduced 19.71%,23.92%,25.92%,27.82% compared with single treatment group, baicalin may accelerated elimination of norfloxacin in Fenneropenaeus chinensis. The results of eneyme activity showed that APND,GST and ECOD activity lowered gradually until the level of control group in single treatment group while first decreased and then arised in combined treatment group. APND was significantly lower than control group in fifth and sixth days in single treatment group(P<0.05), it was also significantly lower than control group in fifth and sixth days in combined treatment group, while it significantly higher than control group in fifteenth day(P<0.01); ECOD was significantly lower than control group in eighth,tenth (P<0.05) and twelveth days(P<0.Ol) in single treatment group, while it was only significantly lower than control group in eighth day(P<0.05), it was significantly higher than control group in fifteenth day(P<0.01); GST was significantly lower than control group in fifth,sixth and eighth days in single treatment group(P<0.05), while it was only significantly lower than control group in fifth and sixth days(P<0.05), it was significantly higher than control group in fifteenth day(P<0.05), in other times they had no significantly difference with control group(P>0.05). we can see that baicalin may accelerated elimination of norfloxacin by inducing drug metabolism enzymes such as CYP450s and GST in Fenneropenaeus chinensis.