| RESEARCH BACKGROUNDEnvironment pollution of present urbanization and industrialization has not only raised the plumbi level in blood (Pb-B) of Chinese people far higher than that of industrialized western nations, but also altered the saturnine characteristics of the people. The acute occupational disease of saturnine gradually gives way to the epidemic disease of moderated raised Pb-B level which severely affect the growth and development of children as well as the health level of adults. At the same time, the researches on saturnine both at home and aboard remain at a slow pace of advancement. The clinic medication for the treatment of saturnine is only complexing agent as the major. This drug has the positive clinic efficacy with quick feature of plumbi-expelling, but it has a strong adverse reaction and inconvenience in caplendus. It is not suitable choice for the preventive measures of the disease. As the alteration of the characteristics of saturnine, the research and development of plumbi-expelling agents should also moves from rapid treatment drugs of plumbi-expelling to the preventive medicine for Pb-B level as well as plumbi-expelling treatment drugs with better efficacy and less side-effect and convenience in caplendus. The study of kinetics of plumbi within human body has proved that the livers have a strong capacity of plumbi secretion and the plumbi level in bile is 100 to 400 times higher than that in blood. The plumbi is driven to the intestinal tract and then re-absorbed to the blood via intestinal-hepatic circulation; little is discharged out of body. Thus suppose some certain in-taken drug in the intestinal tract combining with the plumbi and form an indissolvable compound or the drug can absorb the plumbi, which can block its intestinal-hepatic circulation and re-absorbance, hence to discharge a greater quantity of plumbi that secreted by the bile through stools and reach the goal of expelling the plumbi from our body. Activated carbon is a solid absorbent with great specific surface; it can absorb the organic complexion of heavy metals and also, under certain conditions, can directly absorb the ion of the metal. In the early 90s of last century there were some reports on plumbi-expelling through intestinal tract with absorbents, but without further information or systematic study.OBJECTIVESAccording to the features of intestinal-hepatic circulation of the plumbi, the present study intend to prove the hypothesis that activated carbon could absorb the bile-secreted plumbi in the intestinal tract thus achieve the goal of expelling of plumbi and preventing the saturnine. The major focus of our study would be on the observations of the effects of activated carbon per os in expelling the plumbi within blood, its changes on the trace elements of the organs, its effects on the plumbi-damaged rental functions its influences on the plumbi-poisoned rats in their growth and development, and anti-lipid peroxidation and so on, thus study the efficacy and mechanism of the activated carbon in expelling plumbi via intestinal tract. On the basis of the observations, the comparison between the new praparatum of intest-bioadhension agents of activated carbon and ordinary activated carbon on plumbi-expelling effects in plumbi poisoned models of dogs. The further possibility study is made to confirm the hypothesis that the activated carbon can expel the plumbi in intestinal tract by means of blockage of it intest-hepatic circulation, also aims at founding of the theoretical support and experimental foundation for the screen the narrow spectrum gastrointestinal tract plumbi expelling drug for the clinic treatment and prevention of the lead-poisoning.METHODS1. Prepared artificial gastric juice and artificial intestinal juice with PH values 2.0 and 2.8 respectively, and assayed the changes of metal ions levels of plumbi, zinc, cuprum and ferrum in the solutions circa the adhesion of activated carbon. Measure the adsorptive capacity and drew the adsorption isotherm, hence make the judgment whether the activated carbon in vitro, had the selectivity in adhesion of the four metal ions.2. Randomly divided the 60 rats into 6 groups (10 rats for each) respectively. Group A served as the normal control group, B as the plumbi-poisoned control group, C as plumbi-poisoned+activated carbon treated (at lower dosage) group, D as plumbi-poisoned+activated carbon treated (at middle dosage) group, E plumbi-poisoned+activated carbon treated (at higher dosage) group, F as plumbi-poisoned+ complexing agent treatment group. The experiment lasted 50 days, in the 20th and 50th days of the experiment, the vena caudalis blood tests of the rats were made respectively. In 50 days, the rats were sacrificed and the organs of livers, brains, spleens and kidneys were collected respectively. The metal ion levels of plumbi, zinc, cuprum, and ferrum in the blood samples and the organ specimens were measured through atomic absorption spectrometry, so as to study the treatment efficacy and advantages of activated carbon in expelling plumbi of saturnine animal models and to identify the possibility of selectivity for the adhesion of the four metal ions in vivo.3. In the 50th day of the above experiment, 24-hr urine and vena caudalis blood were collected respectively in testing zinc protoporphrin of blood, serum creatinine (Scr), blood urea nitrogen,δ-aminolevulinic acid of urine, urine total protein,β2-microglobulin in urine, N-aminoβ-D glucosaminidase and other functional index of the kidney, and also kidney histology tests and comparision study with these index in complexing agent treatment group, to appreciation of the repairing effect and advantages of activated carbon for the plumbi-damaged kidney.4. With 40 initial delactation male rats, four groups (10 rats at each) were divided at random. Group A was served as the normal control, B as the plumbi-poisoned control, C as plumbi-poisoned+activated carbon treatment group, D as plumbi-poisoned+complexing agent treatment. The experiment last 12 weeks, in monitoring the newly-born rats of their changes in body weights, growth conditions, and their development of major organs as well as their weights. Tests of the biochemistry index of MDA, SOD, GSH, GSH-Px and so in both blood and tissue specimens for pre-and post-therapies. Thus studied and assayed the influence of activated carbon on the plumbi-poisoned rats in their growth and development and lipid peroxidation damage after the plumbi-expelling process.5. With 24 dogs divided into 4 groups (6 each) at random. Group A served as normal control, B as plumbi-poisoned control, C as plumbi-poisoned + ordinary activated carbon treatment group, while D as plumbi-poisoned+activated carbon in intest-bioadhension agent treatment. The experiment lasted 30 days. Urines, stools and venous blood (VB) samples were collected at 10th, 20th and 30th days. The plumbi levels of the samples were assayed with absorption spectrometry. The experiment were intended to make further study on the activated carbon of the plumbi-expelling effect via intestinal tract for another kind of animal, and to test the efficacy of our newly developed intest-bioadhension agent in plumbi-expelling for plumbi-poisoned dog models, also to make the comparison with that of the ordinary activated carbon agents, hence to identify the better efficacy and advantage of our intest-bioadhension activated carbon in practical experiment.RESULTS1. A through adsorption capacity determination of activated carbon to several metal ion adsorption capacity, and during the simulation and artificial gastric intestinal fluid conditions adsorption capacity slightly different, but little change; At low concentration, the activated carbon several metal ions adsorption isotherm almost no difference. There were no selective. on the adsorption capacity in note different PH and low concentrations of metal ions by activated carbon impact in vitro.2. The rat plumbi-expelling model experiment of the plumbi poisoned rats exhibited that after the saturnine, the Pb-B level and plumbi levels in the organs of liver, brain, spleen and kidney were significant increased, and after the treatment of activated carbon, the Pb-B level was significant lowered than that of plumbi poisoned control group, and the plumbi-level in above organs were also decreased significantly. This indicated that the intake of activated carbon via gastrointestinal tract had a better plumbi-expelling efficacy. Besides the plumbi levels in liver and kidney of activated carbon treatment group were lower that these of complexing agent treatment group, while in the other organs the results were opposite. In the process of plumbi-expelling, the activated carbon decreased the levels of other trace elements within the organisms but showed a better selectivity than that of complexing agent.3. Compared the changes of Scr, BUN, TP,β2-MG, NAG,δ-ALA, RBP of rats damaged by the saturnine treated with both complexing agent, dimercaptosuccinate sodium (DMS) and activated carbon, we found that the activated carbon displayed a better repairing functions on the damages of kidney and also a greater improvement on the pathologic structure of the kidney tissues that that of the complexing agent.4. The plumbi-poison process obviously suppressed the growth of the immature rats, slowed the pace of their body-weight increase, inhibited their development of brain via lowering the weight of their brains, restrained their immune function with a lower weight of spleen; and also damaged the liver and kidney by increase the weight of organs. With the treatment of both activated carbon and complexing agent, the above indications could be improved at certain degree and without any significant differences. But as for the restoration of kidney weight, the activated carbon group showed significant better efficacy than that of DMS group. We also proved that activated carbon expelling plumbi via intestinal tract absorption, could greatly improve the enzymatic indications within the blood that related to the anti-lipid peroxidation; which were similar to these of complexing group, and no statistical differences. As for the kidney and the restoration of enzymatic indication that related to anti-lipid peroxidation, the activated carbon group statistically significant showed a better effect that that of the complexing agent group. This showed expelling plumbi via absorption within the intestinal tract could improve the damaged organs and could quickly restore the activities of various enzymatic system of anti-lipid peroxidation, and showed an even better repairing on the kidney restoration.5. The plumbi poisoned groups, when compared with empty normal control group, showed higher Pb-B levels, and plumbi levels at both stools and urines were significant higher that later, this showed the successfulness of the model establishment. Both treatment groups, when compared with the plumbi poisoned control, Pb-B level significantly lowered, plumbi level in stools samples were higher and the plumbi discharge via urine were lower; both showed significant differences. All these showed that both agents have a better plumbi-expelling effect in the intestinal tract. But the activated carbon in intest-bioadhension agent, when compared with the ordinary activated carbon agent, the Pb-B level was lower and plumbi level in stool discharges were higher than those that the later group and also showed statistical differences. But the plumbi level in urine discharges showed no statistically significant in both.CONCLUSIONS1. Activated carbon is a broad spectrum absorbent, it shows no selectivity in absorbing plumbi, zinc, cuprum, ferrum and other necessary trace elements of the body in vitro.2. Activated bio charcoal absorbent in gastrointestinal tract can significantly lower the Pb-B level and plumbi level at liver, brain, kidney and other organs of rats.3. Activated bio charcoal absorbent in gastrointestinal tract in treatment of plumbi damage of kidney can have a better effect of recovery. It can obviously improve the renal functional indications such as blood Scr, BUN and TP,β2-MG, NAG,δ-ALA, RBP of urine among the plumbi poisoned rats. When compared with these of DMS treatment group, the activated carbon shows even better results which may be related to the access of plumbi-expelling.4. Activated charcoal absorbent in gastrointestinal tract can obviously improve the growth and development of plumbi poisoned rats and their restoration of organs weights. It can promote the enzymatic activity of anti-lipid peroxidation, especially especially for the restoration of the kidney.5. Intest-bioadhension agent showed better plumbi-expelling effects on plumbi poisoned dog models than that of ordinary activated carbon. It may due to prolong residence time of the new agent in the intestinal tract and enhanced the affinity of the activated carbon with the intestinal mucosa thus reinforced the effect of plumbi-expelling.
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