Primarty Study On The Toxicity And Pharmacodynamics Of Poly I:C

Poly I:C, a double-stranded synthetic ribonucleic acid (RNA) generated mixingequimolar quantities of polyribocytidylic acids and polyriboinosinic acids, was firstdescribed by Davis and Rich in 1958 and reported by Field et al. in 1967 to give rise to ahigh titer of interferon in serum of animals which had received a little of materialintravenously. Subsequent studies have amply confirmed that Poly I:C is an effectiveantiviral, anti-tumor and immunoregulatory agent both in vitro and in viro and is the mosteffective synthetic interferon inducer generally available. It commonly has been used forthe treatment of viral and tumorous disease in human clinical medicine, but there were fewreports in veterinary. In this article, primary study on the toxicity and pharmacodynamicseffects of Poly I:C was performed to provide theoretical foundation for its clinicalapplication in veterinary practice.1 Study on the toxicity of Poly I:CThis experiment was designed to investigate acute toxicity, accumulative toxicity,sub-chronic toxicity and mutagenic toxicity of poly I:C injection in mice. Acute toxic effectand accumulative toxic effect of poly I:C injection were detected by modified Kabermethod and accumulation coefficient method respectively. The mice were injected withpoly I:C subsequently for 28 d to evaluate the sub-chronic toxicity. Micronucleus test andsperm structural test of Poly I:C injection were carried out in KM mice to evaluate itsmutagenic toxicity. It was tested out that the half death quantity (LD₅₀) was 59.73mg·kg-1·BW-1 and the 95% confidence interval was 29.49～120.97 mg·kg-1·bw-1. Theaccumulative coefficient (K) was beyond 5.3. The toxic signs of the mice exposed to highdose that included chill, anorexia, depression and poor gain weight during the first week inthe subchronic toxicity test. The results of blood routine examirtation and biochemicalindex of blood indicated that HCT, HGB and ALB of the high groups were significantlower than the control. The results of pathohistology checks indicated that the liver wasslightly inflamed in high groups. The results showed that Poly I:C injection has nomutagenic toxicity to KM mice, but had some toxicity when administered with a highdosage for a long time. 2 Effects of Poly I:C on the immune function in chicksOne hundred and twenty of Roman cocks of 15 days old were randomly divided into 4groups, which were Saline-treated group, low dose group(Poly I:C,0.5 mg/kg), mediumdose group(Poly I:C, 1 mg/kg), and high dose group(Poly I:C, 2 mg/kg). Some immuneparameters were detected on the 2nd day and 10th day after treatment with Poly I:C. Theblood-biochemistry indexes were detected on the 2nd day, 6th day and 10th day aftertreatment. Eighty 50-day-old chicks were randomly divided into 4 groups with 20 chicks ineach group. Chicks were administrated Poly I:C by intravenous injection, intramuscularinjection, nose or oral administration respectively. Blood were collected via wing vein atdifferent time-point to determine the ChIFN-αconcentration by ELISA. The results showedthat both the concentration of TP and the number of LYM in the high dose group werehigher than that in the Saline-treated group significantly (P＜0.05). The concentration ofGLP, rate of EtRFC and the Index of bursa in medium group and high group were alsomarkedly higher than that in the control group (P＜0.05). All groups except oraladministration group reached their maximum ChIFN-αconcentration quickly, which was4-7 times higher than their concentration before administration, and then decreased rapidly.However, in the oral administration group, the concentration of ChIFN-αdid not varyobviously. It was concluded that poly I:C can enhance the immune function of chicks.3 The clinical test of Poly I:C against Newcastle disease600 49-day-old chicks were selected to evaluate the prophylactic and therapeuticefficacies a of Poly I:C gainst Newcastle disease virus. 540 chicks were divided 3 groupsfor early prevention, prevention and treatment test group. Positive group and control groupwere also set up with the other 60 chicks. The mortality rate of chicks in experiment groupwas lower than the positive group significantly(P＜0.05/0.01). And the symptoms of chickstreated with Poly I:C in early prevention examination appeared much later than the positivegroup. The prophylactic effect of Poly I:C was better than it's therapeutic effects toNewcastle disease virus. These results suggested that poly I:C provides a highly effectiveprophylaxis against Newcastle disease infection in chicks.