Toxic Effects Of Lead To Mice Liver, Kindey And Brain

Lead is a widely used metal which has been associated with human activities for 5000 years, but it is simultaneously a versatile, subtle, and persistent poison. Exposure to lead is an environmental threat to health and to physical development in young children. The widespread environmental contamination makes this ubiquitous neurotoxicant a public health problem of global magnitude.Lead is a poison that affects virtually every system in the body with the most deleterious effects on the hemopoietic, nervous, reproductive systems and kidney function. Microcytic hypochromic anemia is often diagnosed in victims of lead exposure. Headaches, poor attention span, irritability, loss of memory, and dullness are the early symptoms of the effects of lead exposure on the central nervous system. The most serious manifestation of lead poisoning is acute encephalopathy, the symptoms of which include persistent vomiting, ataxia, seizures, pappiledema, impaired consciousness, and coma. Characteristics of chronic lead nephropathy include progressive interstitial fibrosis and the reduction in the glomerular filtration rate irreversibly. Otherwise, lead typically causes increased blood pressure in adults, constipation and colic. Reduced sperm counts and motility have also been associated with chronic lead exposure. Because of the ability of crossing placenta, the effects of lead on foetus also can't be ignored.In spite of the extensive documentation of the toxic effects of lead , a complete and detailed explanation on the mechanisms of lead toxicity have not be defined yet. So this study aimed at to investigate the effects of lead on some organs(especially on liver) in mice, at aspects of ultrastructure and protein expression.According to the experiment design, twenty five ICR mouse were randomly assigned into five groups and administrated by oral gavage with 0,10,50,100 and 500 mg-kg"1 body weight of lead acetate every other day for successive 28 days. The tissue slices of liver > kidney and brain were made for ultrastructure observation. Meanwhile, the expression of p53, Bax and Bcl-2 in liver were measured by western blotting. DNA extracted from liver tissue was estimated by agarose gel electrophoresis.The results were shown as below:1. Each organ coefficient was't changed compared to the control except for liver. The liver/body coefficient was significantly higher than that of control (p<0.05) at the doage of 500 mg-kg"1 body weight.2. It can be observed that nuclear chromatin condensation, nuclear membrane shrinkage, mitochondria and endoplasmic reticulum swelling distinctly in mouse liver exposed to lead. Abnormal nuclei also existed in kidney and brain tissue at the high dosages. Meanwhile, microvilli were damaged on the epithelial cell of Renal tubule.3. The expression of p53 and Bax were significantly higher than that of control (p<0.05) at the doage of 10 mg-kg"1 body weight. But as the increasing of dosage, they were decreased steadly and significantly lower than that of control (p<0.05) at the dosage of 500 mg-kg"1 body weight. The expression of Bcl-2 showed no difference in lead-treated groups compared with control group except for the highest dosage group. It was significantly lower than that of control(p<0.05). The ratio of Bax/Bcl-2 was significantly higher than that of control (p<0.05) at the doage of 10and 50 mg-kg" body weight.4. Only genome DNA was observed by agarose gel electrophoresis . Conclusions:1. The liver/body coefficient rose at the doage of 500 mg-kg"1 body weight. It indicated that compensatory hypertrophy of liver may be occurred.2. The ultrastructure of liver > kidney and brain tissues were abnormal. The changes indicated that lead may have an influence on the function of these organs.3. Lead had an affect on the expression of p53. P53 were up-regulated at the low dosageClOmg-kg"1). The change may affect a series of events associated with p53.4. The rise of Bax/Bcl-2 ratio in mice liver may be associated with hepatocytes apoptosis.