Reproductive Toxicity Of Cadmium To Rats And Function And Mechanism Of Huang Qi Ameliorating This Toxicity

Background:In 21^st century heavy metals pollution is one of the most serious problems in the world.In general,it has been demonstrated to cause toxicities through environmental exposure while in humans,occupational exposure is major concern along with environmental exposure.Cadmium(Cd)has widely been reported to cause reproductive toxicities in vertebrates,but the complete mechanism of reproductive toxicity caused by Cd is not fully understood and when the toxicity is induced,could the toxic effect be reversed at gene level?Previous literature has not addressed questions like this,particularly in steroidogenic pathway.Considering these problems,we design the current experiment,in which we used Huang Qi,a well-known traditional Chinese Medicine which is used for centuries because of its bioactive chemicals and pharmacological uses.This plant is reported to control oxidative stress,renal and hepatic toxicities,inflammation etc.whereas Cd induces its toxic effects by oxidative stress,it damages liver,kidney,nervous system,and all the body.1.Damage to the Testicular Structure of Rats by CadmiumThe current study was divided into two parts,in first part we wanted to select best possible dose for our experiment.For that purpose,we divided adult Sprague-Dawley rats into four groups,the first group served as control group and the remaining three groups were treated with oral gavage of 5,10,and 15 mg/kg of Cd per day for 17consecutive days.Our results reveal that there was a significantly low weight gain in10 and 15 mg/kg groups,whereas 5 mg/kg group had gain same weight as control group.The histological results show major structural deformities in the testes of rats,where the tunica albuginea,the interstitial space,and the tubular lumen diameter were significantly reduced,and the epithelial height and seminiferous tubules diameter was increased in Cd treated groups.The comet assay in the sperms showed a significant variation in the total length and head length in all Cd treated groups,which shows damage in heritable DNA,however the total sperm count was not significantly changed in Cd treated groups as compared to control.Overall the three Cd treaded groups produced severe histological and DNA damages,but in 15 mg/kg groups,some animals died in first try,while the 5 mg/kg group induced variations,but there was no change in animal weight or daily sperm production,with a very minor histological damage,so10 mg/kg/day dose was selected for 2^nd part of the experiment.2.Protective Effects of Huang Qi Against Cadmium-Induced Damages in Ovaries of RatsIn this part of this study,we wanted to find,if the toxicity induced by Cd could be alleviated by co-treatment of animals with Cd and Huang Qi.For that reason,we divided animals in 8 groups,in which the first group served as control group,the 2^ndgroup was treated with oral gavage of Cd(10 mg/kg/day),three groups received different doses of Huang Qi(10,20 and 50 mg/kg/day),and the remaining three groups received both Cd(10 mg/kg/day)and different doses of Huang Qi((10,20 and 50mg/kg/day)respectively.Our results indicate that Cd and Huang Qi have no effect on anthropometrical parameters,except the estrous cycle,which is severely damaged in Cd treated animals.Cd not only prolonged some stages of estrous cycle,but the cyclicity was also damaged and the estrous cycle was not in continuous manner,whereas Huang Qi not only control the cyclicity,but the overall cycle was prolonged.This could also be seen in histopathological examination of ovaries,the 50 mg/kg of Huang Qi groups have extra numbers of corpus luteum.The Cd treated animal have higher number of blood vessels in medulla of ovary which is partially alleviated by Huang Qi.In steroidogenic pathway,the expression of Star gene was significantly increased and PKA gene was decreased by Huang Qi.The Cyp17a1 and Cyp19a1 genes showed dose-dependent variations to Huang Qi,their expression was decreased by high and the low doses of Huang Qi but increased by the medium dose of Huang Qi.In Cd group the Cyp17a1 expression was significantly reduced whereas in the Cyp19a1 was not affected.Based on these results we conclude that Cd induced damages to structural morphology and estrus cycle of rats,which are alleviated by Huang Qi.ConclusionThe results of current experiment show that the damages induced by Cd increases with the increase in Cd concentration,and even a very small concentration of Cd above certain level is enough to not only damage the physiology but could kill the animals.In2^nd half of the experiment,we observed that the toxicity could be alleviated by using ethanolic extract of Huang Qi.Even though the concentration of inhibin,estradiol,and progesterone was not affected by Cd,severe variations were noted in relative expression of genes involved in steroidogenesis.