Studies On The Toxicity And Pharmacodymics Of The Injiection And The Microcapsule Of Poly I:C

As a copolymer of polyinosinic acid and polycytidylic acid,Poly I:C (polyinosinic:polycytidylic acid) is an efficient inducer of interferon and plays a role on the broad-spectrum antiviral,provoking swallow,adjusting immunity,and activity of antineoplastic,antibacterium and antitozoon.In human clinical medicine,Poly I:C exhibit obvious effect especially in treating hepatitis,herpesvirus infection and some neoplastic disease.Only a few Puly I:C reports have been reported in treating swine plague and duck plague in veterinary clinical medicine.The toxicity and pharmacodymics of the injection and the microcapsule of Poly I:C were discussed in this article to provide rationale of exploitation and use of Poly I:C in veterinary clinical medicine.The common toxicity and mutagenic action of Poly I:C in mice To investigate the toxicological effect of Poly I:C on animals,the acute toxicity,accumulative toxicity, inferior-chronic toxicity,mutagenic actions of Poly I:C injection to Kunming mice were studied in this paper.The results revealed that the LD₅₀ of Poly I:C injection in mice is 0.083 5 g·kg^-1,95%confidence interval is 0.066 28～0.105 32 g·kg^-1;Poly I:C injection in mice showed the lower accumulation characteristics with the accumulative coefficient K＞5. The mice showed Poly I:C tolerance with small dosage and long time exposure to Poly I:C injection;The inferior-chronic toxicity of high dose group in mice revealed that Poly I:C injection result in the toxic responses characterized by diarrhea,intestine enlarged with watery contents.Middle dose group mice of Poly I:C injection just showed the lower toxic response and there was no obvious difference in low dose group mice;The negative results of the cellular medullares micronucleus test and the teratospermia test demonstrated that Poly I:C injection has low mutagenic action.Effects of Poly I:C on the IFN-αand Immune Activities of Broilers Challenged by Newcastle Disease Virus Broilers challenged by Newcastle disease were injected Poly I:C and detected its' IFN-αin blood serum and specific and non-specific immune function. The results reveal that the mortality of 0.02 mg/kg·bw,0.01 mg/kg·bwå’Œ0.005 mg/kg·bw dose groups is 40%,20%and 26.7%,which are all lower significantly(p＜0.01) than that of positive control group(63.3%).Effects of Poly I:C on the IFN-αinduction advance as dosage increase,but when exceed some limit,effects are inhibited.Poly I:C has obvious effect on increasing CD3⁺ cell in peripheral blood,but doesn't exhibit effect on increasing titer of antibody of NDV.It seems that on one hand,Poly I:C reduces NDV's damage to lymphocyte by inducing IFN-α,on another hand,anticipates and increases cell immunity of organism,so it can counteract virus.But Poly I:C doesn't show obvious effect on humoral immunity.Inductive effects of IFN-αand immune activities by poly I:C microcapsule I n Newcastle Disease Virus infected broilers To evaluate anti-virus effect of Poly I:C microcapsule,IFN-αlevel and the specific and non-specific immune indicators were detected in Newcastle disease virus(NDV) infected broilers after oral administration of Poly I:C microcapsule.The results showed that the therapeutic efficacy of Poly I:C Microcapsule is similar to that of Poly I:C injection.It reveal that nucleinase in digestive tract do not show obvious effect on the degradation of Poly I:C microcapsule during absorption of Poly I:C.IFN-αconcentration increased with dosage of Poly I:C microcapsule in a limited range,while IFN-αlevel decreased overen the dosage of 0.2 mg/kg·bw.Poly I:C microcapsule administration display obvious effect on improvement of cell immunity but no exhibition on adjusting humoral immunity.