| ObjectiveWith the development of technology, biotoxicity aroused by aluminum (Al) was revealed and generally attended. Aluminum is a ubiquitous metal in nature. It can be ingested in everyday living, cumulate in vivo and exert various of toxicity effect. Now its toxicity on nervous system was generally recognized. Many experiments showed aluminum might be related to various neurodegenerative disorders, such as Alzheimer's Diseases (AD), dialysis encephalopathy, and so on. It can also disturb metabolizm balance of calcium and phosphorus, restrain vivo anti-oxidation system, cause bone damage and weaken of productive function, anaemia, and other disease. Aluminum could arouse reproductive disorder by restraining body anti-oxidation system, changing activity of enzymes, interfering genetic material synthesis, and so on. Chelators have been useful to treat metal-overload diseases. People have tried many chelators for aluminum eliminating, but there was none appeared perfect. In the following experiments, DFP (deferiprone,1,2-dimethyl-3-hydroxy-4-pyridone) was used as a new type of aluminum chelating agent in animals. With Wistar rats as experimental animals, we investigated the mechanism of DFP protecting productive system, to provide foundation for seeking a safe and efficacious medicine for aluminum overload.Methods1 Animal experiment35 male Wistar rats (weight ranged from 180g to 220g) were used as experimental animals. Animals had free access to food and water. They were randomly divided into 5 groups:negative control group, aluminum group, low, mid, and high dose DFP groups. To make aluminum chronic toxicity model, rats were given drugs by gavage, weekly for 5d, interval 2d after administration. Animals were subjected to 172.5 mg/(kg·d) of aluminum chloride daily for 8 weeks except negative group for normal saline. Then DFP groups were given a dose of 13.82,27.44 and 54.88 mg/(kg·d) of the DFP solution, while the aluminum group and negative group were given normal saline.2 weeks later, after 24 hours for last gavage, we sacrificed animals, removed testicles and epididymis, stored them in refrigerator for following experiments.2 Rats treatment and common conditionAnimals were under observation and weighted everyday, then gavaged by different doses according to their weight. Body weight of animals in groups were curved and compared. After sacrificed animals, we dissected them and removed testicles and epididymis. Tissues were used for detection.3 Effect of DFP in expelling aluminum and essential elements in testiclesThe testicle tissues were digested by microwave digestion for following analysis of aluminum by graphite furnace atomic absorption spectrophotometer and zinc, copper, iron, calcium and magnesium elements concentration by flame atomic absorption spectrophotometer. The aim of this experiment was to study DFP's effect of eliminating aluminum and influence on essential elements.4 Effect of DFP in recovering the anti-oxidation system damaged by aluminumThe activity of superoxide dismutase (SOD) and the content of malonadehyde (MDA) in the testicle tissues of the rats were determined in every group. The aim was to investigate the effect of DFP on recovering the antioxidation system in testicle.5 Effect of DFP in recovering marker enzymes of testicle impacted by aluminumThe activities of lactic acid dehydrogenase (LDH) andβ-glucuronidase (β-G) in the testicle tissues of rats were detected in every group. The aim was to investigate the effect of DFP on recovering marker enzymes of testicle.6 Effect of DFP in recovering germ plasm damaged by aluminumWe obtained rat blood for polychromatic erythroblasts micronucleus test, to investigate the effect of DFP on recovering genic damage by aluminum. Effect of DFP for germ cell could be concluded.7 Effects of DFP in recovering sperm damaged by aluminumEpididymis was cut in saline, coated on slide, stained by eosin to make spermatozoa smear. Then smears were observed under light microcope. Normal and aberrated spermatozoa were counted to calculating aberration rate.8 Effects of DFP in recovering testicle tissue damaged by aluminumAfter fixed, testicle was sliced and stained by hematoxylin-eosin (HE) to make pathological section. Then sections were observed under microcope.Results1 Effect for common condition of ratsAnimals appeared in good condition. No significant difference was found in body weight changing trend of groups. No significant difference was found in weight of testicle and epididymis and organ coefficients.2 Effect of expelling aluminum and essential elements in testiclesAluminum content in rat testicle of aluminum group was significant higher than negative group (P<0.01), and higher than DFP groups. No statistical signification was found among groups in contents of iron, zinc, calcium, magnesium and copper.3 Effect of DFP in recovering the anti-oxidation system damaged by aluminumThe SOD activity in rat testicle of aluminum group was significant lower than negative group (P<0.05). With the DFP dose increased, the activity of SOD in testicle showed an upward tendecy, while MDA content presented a downward tendecy. The activity of SOD was higher, and MDA content was lower in high dose DFP group than in aluminum group (P<0.05) and (P<0.01).4 Effect of DFP in recovering marker enzymes of testicle impacted by aluminumThe P-G activity in rat testicle of aluminum group was significant lower than negative group (P<0.05). With the DFP dose increased, the activity ofβ-G in testicle showed a upward tendecy. The activity ofβ-G was higher in high dose DFP group than in aluminum group (P<0.05). Activity of LDH was higher in negative group than other groups (P<0.05). No statistical signification was found in activity of LDH among DFP groups and aluminum group.5 Effect of DFP in recovering germ plasm damaged by aluminumThe micronuclear rate of peripheral blood polychromatic erythroblasts was significantly higher in aluminum control and doses of DFP groups than in the negative control group (P<0.05). The micronuclear rate in middle and high dose of DFP groups was lower than in aluminum control group (P<0.05). The difference of erythrocyte micronucleus rates between in low dose DFP group and in aluminum control group was no significant.6 Effects of DFP in recovering sperm damaged by aluminumThe spermatozoon aberration rate in aluminum control group was significantly higher than in negative control group (P<0.05). The rate in DFP groups was lower than aluminum control group. With the DFP dose increased, the spermatozoon aberration rate showed a downward trend. The spermatozoon aberration rate in aluminum control group and in middle, high dose of DFP groups was significantly different (P<0.05).7 Effects of DFP in recovering testicle tissue damaged by aluminumRelative to the negative control group, the rat testicle tissue of aluminum group was damaged. It was observed under microscope as follows:the contorted seminiferous tubules were significantly atrophy; the tubal wall was thinner; the layer and the number of cells got fewer; in some part of tubal wall, cells fell off and there became a cavity. DFP groups had different degrees of recovery.Conclusions1. DFP can significantly promote the discharge of aluminum in rats' testicular tissue; reduce tissue level of aluminum, while it had no influence to the essential trace element.2. DFP can reduce lipid peroxidation from occurring in aluminum-loaded rat testis, to maintain normal physiological functions.3. DFP can recover rats'activity of some testis marker enzymes depressed by aluminum, to improve reproductive function.4. DFP can depress rats'erythrocyte micronucleus rate and spermatozoon aberration rate raised by aluminum, to recover the damage of genetic material.5. Observed under microscope, visible pathological damage can be caused by aluminum in rat testis tissue, while DFP has a significantly recovering function.In conclusion, DFP can improve the damage of rat's reproductive function caused by aluminum, to display its protective effect on reproductive system.
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