Study On The Bone Damage Of Co-exposure To Lead Acetate And Cadmium Chloride On Rats

Lead and cadmium are the most common heavy metal pollutants in the environment and cannot be degraded. In recent years, with the frequent human activities, especially the development of modern industry, the production and use of lead and cadmium were increasing in the industry, while the concentration of lead and cadmium showed a rising trend in the living environment. Lead and cadmium are often coexist in artificial and natural sources resulting in compound pollution. So lead and cadmium joint exposure received a great attention to the harm of human health. Because lead and cadmium are accumulative toxicants, bone is the target organ and accumulation areas by lead and cadmium toxic injury. At present, the study on Pb and Cd toxicity is limited to individual exposure, and combined toxicity of lead and cadmium is still lack of comprehensive data, especially in bone. In this study, we present a comprehensive toxicological evaluation on Pb and Cd co-exposure by performing acute and 90 day sub-chronic oral toxicity studies in SD rats. By measuring changes in bone mineral density and metabolism in rats and other indicators of pathological changes in the bones of rats, the evidence that the mixed lead and cadmium poisoning caused by toxic effects of bone was provided. Main results for this study are as follows:1. Study of acute toxicity of lead and cadmium combined on bone of ratsIn order to study the effects of acute toxicity of lead and cadmium combined on bone of rats. The experimental rats that were given the different mixture of solutions lead nitrate and cadmium chloride according the method of equitoxic ratio mixing, rats were exposed by gastric gavage. The modified Bliss method was used to determine median lethal dose (LD50) of lead and cadmium combined in the acute toxicity test and then histopathological and bone mineral density of the bones in both the test group and the control group were analyzed in the accumulative toxicity test. The results showed that LD50 of combined exposure of lead and cadmium was 2696.54 mg/kg, and the 95% confidence interval was 2162.00-3362.89 mg/kg. In the test groups, different degrees of dilation and congestion in the capillary vessel of marrow cavity and the exudation of inflammatory substances within the lumen were observed under the light microscope. However, there was no significant difference in the bone mineral density between the test group and the control group (P>0.05). In conclusion, the acute toxicity of combined effect of lead and cadmium had an additive effect and certain toxic effects on the hematopoietic system of the bone.2. Study of subchronic toxicity of lead and cadmium combined on bone of ratsEighty rats were assigned randomly to a control group and three experimental groups that were given the mixture of Pb(NO3)2 and CdCl2·2.5H2O by gastric gavage at doses of 0 mg/kg body weight (b.w.) (Group Ⅰ, to serve as a control),29.96 mg/kg b.w. (Group Ⅱ, 29.25+0.71),89.88 mg/kg b.w. (Group Ⅲ,87.74+2.14), and 269.65 mg/kg b.w. (Group Ⅳ,263.23+6.42) for at least 90 consecutive days. After exposing30d、60d、90d of the experiment, six rats of each group were randomly selected. The rats were housed in individual metabolic cages for 24-h urine collection. All rats were anesthetized with anhydrous ether and then blood samples were collected from the heart. Finally, Rats that fasted were sacrificed by femur and tibia dissection.2.1 Effects of combined subchronic lead acetate and cadmium chloride on bone metabolism in ratsThe calcitonin (CT) and parathormone (PTH) were tested in serum as calciotropic hormones markers, and the mineral status of the serum, urine and bone, including Ca and Pi concentrations or content, was evaluated. The markers of bone formation and resorption were determined to estimate the rate of bone turnover. These results were indicated by a significant (P<0.05-0.01) increase in BALP, CTX, and PTH concentrations and decrease in CT and OC concentrations. Moreover, the concentrations or content of Ca and Pi in the serum and bone were decreased, whereas those in urine increased. Results indicated that the administration of Pb and Cd induced bone metabolism disorders by decreasing bone formation and increasing bone resorption to destroy the hormonal regulation of mineral metabolism as a result of Ca and Pi imbalance, suggesting that bone formation and resorption were uncoupled.2.2 Effect of joint sub-chronic toxicity of lead and cadmium on bone density, and histopathological evaluationThe rats’ skeletal related variables were measured at the femur, Bone mineral density (BMD) was measured at the tibia and femur region by dual-energy X-ray absorbsiometry. The histopathology of bone was evaluated by light microscope, scanning electron microscope, and transmission electron microscope. The results showed that The BMD and skeletal related variables of rats in the experimental group was significantly lower (P<0.05-0.01) than those in the control group. The histopathological evaluation showed trabecular bone became less; the collagen fiber of bone trabecular arranged in disorder, loose structure and breakage; and the osteoblast showed fewer organelles, focal cytolysis. In general, results indicate that combining Pb with Cd induces bone disorders, and changes the bone structure, increases the risk of osteoporosis.