Local Reactions And Systemic Toxicity Effects Of Intramuscular Injection Of Metallic Mercury On Young Rabbits

Objective:To observe the local and systemic toxicity effects of intramuscular injection of metallic mercury on young rabbits and explore the biochemical indicators of central nervous system injury after mercury poisoning.And providing better understanding of the toxicological changes and further interventions after mercury exposure in children.Methods:Twenty healthy and male New Zealand rabbits（40 days old）were randomly divided into normal control group,low-dose group,middle-dose group,and high-dose group.Each group had 5 rats.Normal saline（NS）0.1mL·kg^-1,and hydrargyrum（Hg）700 mg·kg^-1,1400 mg·kg^-1,and 2800 mg·kg^-1 was intramuscularly injected with a single time.Mental status,eating situation,changes of hair and fecal character of each animal were recorded every day.Weight was recorded and X-ray of local injection site was taken before injection,7,14,21,28 and 35 days after the exposure.The Hg level of blood and urine was detected by inductively coupled plasma mass spectrometry（ICP-MS）analysis.Serum neuron-specific enolase（NSE）and S100B was measured by double antibody sandwich enzyme-linked immunosorbent assay（ELISA）.Indicators of liver and kidney function and serum electrolytes was detected by automatic biochemical analyzer.When there was no obvious diffusion of mercury at the injection site,the tissue of the heart,lung,liver,kidney,small intestine,and local injection sites was taken for H﹠E staining to observe the histopathological changes.Results:The experimental group appeared diarrhea,anorexia and weak reaction 7-14days after administration.Irritability and excretion increased appeared 21 days after administration.The body weight of the high-dose group decreased significantly 21 days after administration compared with the control group（P<0.05）.Some animals formed abscesses and knots at the local injection site.The X-ray showed no obvious diffusion tendency of metallic mercury 28 days after administration,the Hg level of blood and urine increased slowly at the same time,and the symptoms of mercury poisoning persisted.Serum NSE in the high-dose group began to rise 21 days after administration,and was significantly increased from the 28 days in the medium and low dose groups,which were different from the control group（P<0.05）.There was no difference between any two experimental groups.Serum S100B in high-dose group was significantly higher than the normal control group,low-dose group and middle-dose group（P<0.05）14 days after the exposure.Serum S100B in middle-dose group was significantly higher than the normal control group and low-dose group 21 days after the exposure（P<0.05）.Serum S100B in low-dose group was significantly higher than the normal control group（P<0.05）28 days after the exposure.The indicators of liver and kidney function indicated that the total protein and albumin began to decrease significantly 21 days after administration（P<0.05）,and triglyceride,total cholesterol,creatinine and urea nitrogen began to increase about 21 days after administration（P<0.05）,the most significant increase of these indicators was in the medium-dose group（P<0.01）.Serum Na⁺,K⁺,Ca⁺⁺,and Cl^-were significantly decreased 28 days after administration（P<0.05）,and the greater the dose,the more obvious the decrease.Inflammatory infiltration and emphysema were the major manifestations in the lungs.Hepatic damage was mainly manifested as hepatocyte edema and inflammatory cell infiltration.Renal damage was mainly manifested as diffuse proliferative glomerulonephritis.Some metallic mercury could be found in the glomeruli.In the small intestine,thickening of the intestinal wall,hemorrhage,and diffuse villus shedding were observed.A complete abscesse could be seen in the local injection site.Histology showed plenty of microabscesses containing vast dispersed mercury droplets surrounded by abundant neutrophils,macrophages and foam cells.Granulomatous response,hyperplasia,hyperemia and hemorrhage in small vessels also could be seen in the lesion area.Conclusion:Single intramuscular injection of metallic mercury can cause local inflammatory reactions and multiple organ damage.Local pathological envelopment formed,local mercury diffusion and mercury absorption slowed down 28 days after the injection,and the local injection site pathological changes conformed to aseptic inflammation.It also caused central nervous system damage,liver and kidney dysfunction,and electrolyte imbalance.All of these provide a scientific basis for the assessment of clinical conditions and correct intervention to children’s metallic mercury poisoning.