Studies On Protective Mechanism Of Selenium Nanoparticles On Testosterone Synthesis Disorder In Rats Exposed To Nickel

Objectives: The aim of the study is to investigate the protect effects of Nano-Se against Ni-induced testosterone synthesis disorder and discuss the possibly mechanisms.Methods:(1)Forty male adult Sprague-Dawley rats(n=8 per group,weighing220±10g)were randomly classified into five groups as follows,a control group,a nickel sulfate(Ni)group,co-administration groups(Ni+Nano-Se1/2/3,respectively).Ni was administered(5.0 mg/kg b.w,IP)and Nano-Se1/2/3 were given(0.5,1.0 and2.0 mg/kg b.w,orally,respectively)in concomitant for 14 days,and euthanized under ether anesthesia on day 15.The weight of rats was measured every five days.(2)Enzyme-linked Immunosorbent Assay(ELISA)Kit were used to measured the levels of serum testosterone.(3)To determine Nano-Se whether could attenuate Ni-induced testes injury,the hematoxylin and eosin(H&E)were performed.(4)ELISA kits were used to detect levels of 8-OHdG for testicular tissues.(5)The mRNA and protein levels of testosterone synthetases,including StAR,CYP11A1 and 17?-HSD,were analyzed by RT-qPCR and Western Blot respectively.(6)Western blot were performed to assay the protein expression of MAPKs signal pathways,including ERK1/2,MEK1/2,MKK3,p38,MKK7 and JNK.Results:(1)Compared with the control group,the body weight was significantly declined by day 10 and day 15 after Ni-treatments(P<0.05).(2)Compared with the control group,seminiferous tubules exhibited disintegration of epithelium cells,disruption and loss of the number of each stage of sperm cells in Ni group,which were obviously improved in Nano-Se2 and Nano-Se3 groups.(3)Increased 8-OHdG levels induced by Ni were attenuated by Nano-Se in testes.(4)Compared with the control group,testosterone levels were significantly declined in the Ni group(P<0.05),while increased in Nano-Se2 and Nano-Se3 groups when compared to the Ni group.(5)Compared with the control group,the mRNA and protein expression levels of StAR,CYP11A1 and 17?-HSD were significantly suppressed by Ni(P<0.05).Compared to the Ni group,significantly upregulation of mRNA and protein expression levels of StAR,CYP11A1 and 17?-HSD were observed in Nano-Se groups.(6)Total ERK1/2,MEK1/2,MKK3,p38,MKK7 and JNK proteins were not statistically different among the groups(P>0.05).Compared with the control group,p-ERK1/2,p-MEK1/2,p-MKK3,p-p38,p-MKK7 and p-JNK proteins levels were obviously upregulated in the Ni group(P<0.05).Also,phosphorylation ratio(total-proteins/phosphor-proteins)of ERK1/2,MEK1/2,MKK3,p38,MKK7 and JNK were obviously increased in the Ni group(P<0.05).Compared with the Ni group,p-ERK1/2,p-MEK,p-MKK3,p-p38,p-MKK7 levels were obviously downregulated in Nano-Se2 and Nano-Se3 groups(P<0.05),and the phosphorylation ratio of ERK1/2,MEK1/2,MKK3,p38,MKK7 and JNK significantly decreased in Nano-Se2 and Nano-Se3 groups.Conclusions: These results indicate that Nano-Se may ameliorate the Ni-induced testosterone synthesis disturbance via the inhibition of ERK1/2,p38 and JNK MAPK signal pathways.