| Objective: Cadmium is one of the most dangerous heavy metals and is one of environmental endocrine disruptors (EEDs). It had been proved to have toxic effects to several kinds of organs and tissues of laboratory animals and human beings, especially female reproductive system, which was one of the most sensitive tissues to the toxic effects of cadmium. It had been interested many authors who had done a lot of animal experiments, but few studies were concerned about the prevention on cadmium-induced female gonad toxicity. The objective of this research was demonstrated whether Alpha-lipoic acid could antagonize cadmium-induced female gonad toxicity and by which mechanisms it worked. This study was also to provide the evidences to the preventions and treatment of cadmium-induced toxicity.Method:1 Forty Sprague-Damley(SD), adult and female rats were weighted and randomly assigned to four groups based on body weight, the four groups included that the control group, the Cdcl2 group, the low-dose Alpha -lipoic acid(LA) group and the high-dose Alpha-lipoic acid(LA) group. The control animals were injected sc with saline, the other groups were injected sc with Cdcl2 at a dose of 1.0mg/kg body weight for six weeks (five days a week, daily). Then the low-dose LA group and the high-dose LA group were injected with 20 mg/kg and 100 mg/kg LA respectively for two weeks. The Cdcl2 group and control group were injected with 0.9% Nacl at the same time.2 The twentieth day after first dosage, estrous cycle of each animal was observed with once per twelve hours vaginal smears until the end of the test. After finishing the prevention, blood specimens were collected from the heart of the rats and their uterus and ovary were taken out. The level of serum follicle stimulating hormone(FSH), luteinizing hormone(LH), estradiol (E2) and progesterone(P) were evaluated by radio immunoassay (RIA), the changes of cadmium level in serum, ovary and uterus and the activities of glutathion peroxidase(GSH-Px) and superoxide dismutase(SOD) in the ovary were measured, in addition, the ovaries were observed by electron microscope. All data were analyzed with the SPSS12.0 software, including Chi-square test, Q-test, and one-way ANOVA.Result:1 The SD rats of Cdcl2 group have some abnormal appearance within the experiment session, such as: listless, anorexia, diarrhea and the glossiness of clothing hair decreased; it had been found abdominal dropsy and organ accretion in three rats when they were killed. The groups treated with LA consciousness and diet didn't have any abnormal appearance compared with the control group. 2 The estrus cycle in rats: Compared with the control group, both duration of estrus cycle and the duration of diestrum were significantly longer in the Cdcl2 group, it had significant statistical difference(P<0.05), there were no significant statistical difference in the low-dose LA group and high-dose LA group(P>0.05); Compared with the Cdcl2 group, the radio of estrus cycle abnormity was lower in the low-dose LA group and the high-dose LA group, but it had no significant statistical difference(P>0.05); Compared the other estrus cycle, there were no significant statistical difference between groups(P>0.05).3 The content of gonad hormone in serum: Compared with the control group, the level of serum E2 and P declined significantly in Cdcl2 group, it had significant statistical difference(P<0.01); the level of serum P increased significantly in the low-dose LA group than in the Cdcl2 group (P<0.05), the level of serum E2 increased in the low-dose LA group than in the Cdcl2 group, but it had no significant statistical difference(P>0.05), the level of serum E2 and P increased significantly in the high-dose LA group than in the Cdcl2 group, it had significant statistical difference(P<0.01); there were no significant statistical difference of serum FSH, LH between groups(P>0.05).4 The content of cadmium in serum: Compared with the control group, the content of cadmium in serum increased significantly in the Cdcl2 group, it had significant statistical difference(P<0.01); compared with the Cdcl2 group, the content of cadmium in serum declined in the low-dose LA group(P<0.05), and the high-dose LA group declined significantly (p<0.01); there were no significant statistical difference between the high-dose LA group and the control group(P>0.05).5 The content of cadmium in uterus: Compared with the control group, the content of cadmium in uterus increased significantly in the Cdcl2 group, it had significant statistical difference(P<0.01); compared with the Cdcl2 group, the content of cadmium in uterus declined to some extent in the low-dose LA group, but it had no significant statistical difference(P>0.05), there was significantly declined in the high-dose LA group , it had statistical difference(P<0.01).6 The content of cadmium in ovary: Compared with the control group, the content of cadmium in ovary increased significantly in the Cdcl2 group, it had significant statistical difference(P<0.01); compared with the Cdcl2 group, the content of cadmium in ovary declined in the low-dose LA group(p<0.05), and the content of cadmium in ovary declined significantly in the high-dose LA group, it had significant statistical difference (p<0.01).7 The activities of GSH-Px and SOD in ovary: Compared with the control group, the activities of GSH-Px and SOD in ovary declined significantly in the Cdcl2 group, it had significant statistical difference(P<0.01); the activities of SOD in ovary increased in the low-dose LA group than in the Cdcl2 group(p<0.05), the activities of GSH-Px and SOD in ovary increased significantly in the high-dose LA group than in the Cdcl2 group, it had significant statistical difference(p<0.01).8 Morphologically observation: Observing by the electron microscope, primary follicle in the Cdcl2 group show that there were a lot of lipid droplets and some vacuolar degeneration in the cytoplasm, nucleus was irregular, nucleolus was disappeared, mitochondria was edema, the crista of the mitochondria decreased, some cristae were arranged disorderly, even confluence or disappearance, some cell membrane were confluence or disappearance, the rough endoplasmic ret was broaden or degranulated and so on. It is very similar between the groups treated with LA and the control group, while the alteration would more and more lesson with the dose of LA increased.Conclusion:1 The animal model of cadmium-induced female gonads toxicity established successfully, which could further study on toxicities of female gonads endocrine disrupt of cadmium.2 LA can make the ratio of estrus cycle and diestrum abnormity, the content of cadmium in serum, uterus, ovary declined, and the level of E2, P in serum, the activities of GSH-Px, SOD in ovary increased, thus it show that LA extract exerted striking protective effects on cadmium-induced female gonads toxicity.3 The mechanisms of LA against cadmium-induced female gonads toxicity was possibly through enhance antioxidant activity, increased cadmium excretion, decreased testicular cadmium content, restored enzyme activity in the ovary and maintained serum hormone level.4 These findings suggested that LA extract exerted striking protective effects on cadmium-induced female gonads toxicity, moreover the protection would more and more obviously with the dose of LA increased. It had been shown a new inspiration in basal research and clinical medication and supplied a new way in prophylaxis and treatment of cadmium poisoning, but it had to further research the curative dose of LA. |
