Safety Assessment Of Blended Essential Oil LZ307 And Its Treatment On Retained Fetal Membranes In Cows

The retained fetal membrane was one of the important diseases that affected the reproductive performance of dairy cow.The disease has brought great economic loss to our dairy industry.Essential oil is a kind of volatile liquid with strong fragrance and sweet smell was extracted from different organization of plants such as fruit,root,leaf or flower.The essential oil is regarded as an"efficient,safe,stable and controllable"plant-derived drug.It has the functions of antibacterial,antiviral,anti-parasite,antifungal,enhancing the animal immune function,anti-stress ability and improving animals production performance,etc.In recent years,more and more research was carried on bioability of Essential oil.The aim is to investigate the safety of clinical medication dosage of essential oil,evaluate the therapeutic effect of essential oil on retained fetal membrane,and explore the treatment mechanism.The acute toxicity,the chronic toxic effects,safety evaluation,clinical efficacy,and phamacoloical mechanism of plant essential oil was evaluated.（1）The LD₅₀ of the essential oil was 5.50 g·（kg·bw）^-1 and the remarks 95%confidence limit of4.65-4.65-1 g·（kg·bw）^-1,this result showed that the essential oils have no toxicity.In chronic toxicity test of the essential oil,there were high dose group(0.55 g·（kg·bw）^-1),middle dose group(0.11g·（kg·bw）^-1),low dose group(g·（kg·bw）^-1,and blank control group（normal saline）.The rats were administered drugs orally with the designed doses for 28 days.The results showed the feed intake decreased significant difference（P<0.05）,the rats weight gain and water consumption has no significant change（P>0.05）in drug treated groups.To compare with blank control group,only the spleen viscera index was extremely significant difference（P<0.01）,others viscera indexe were not significant change（P>0.05）.Routine blood results showed that the average red blood cell count,hemoglobin content and concentration were extremely significant difference in high dose group（P<0.01）.Serum biochemical results showed sera creatinine content was significant differente（P<0.05）.Pathological test results showed that there was congestion phenomenon in spleen,which showed a dose-defense relationship between dose and the pathological symptoms.In high dose group,hyperemia,swelling in the renal tubular epithelial cells was observed,and liver cell shwed swellen,hyperplasia and visible light blood clot.Heart,lung,thymus gland,uterus,ovaries have no obvious pathological changes.（2）The skin irritation test results showed that the 0.60⁶.00 g·（kg·bw）^-1 of the oil have mild irritation.The dose below 0.12 g·（kg·bw）^-1 have no irritation.Allergy test showed that essential oil have no sensitization to guinea pig skin.Under dose of 5.00 g·（kg·bw）^-1 in essential oils,there were mild irritation and mild inflammation in the uterus of rats.（3）Clinical trial showed that the cure rate on the retained fetal membrane was 72%with 40 mL drug per cow.The blood physiological and biochemical analysis suggested that the mechanism of retained fetal membrane was expelled,which owed to the essential oil may regulat the blood lactate dehydrogenase and alanine aminotransferase,lactate kinase content.According to serum metabolomics analysis,pharmaceutical mechanism of essential oil on the retained fetal membrane maybe through arginine and proline metabolism pathway,ABC transporters result in the fetal membrane discharge.In conclusion,the essential oil have no toxic,but long-term high dose lavage administration will have certain toxic effects on rats;the essential oil has a good security and therapeutic effect,the mechanism of treatment may be related to arginine and proline metabolism pathway,ABC transporters.