Effects Of Polysaccharide From Dendrobium Officinale On The Reproductive Damage In Male Mice Induced By Cisplatin

Background:Damage to the reproductive system can lead to reduced sperm count and decreased quality.The use of chemotherapeutic drugs in treatment cause reproductive damage in male has become common in young people.Therefore,the prevention and protection of reproductive damage has become an increasingly important area of research.Cisplatin?CDDP?is a commonly used chemotherapeutic drug,which has a good therapeutic effects on various tumors.However,severe reproductive damage assoicated with the cisplatin limits its clinical use.Dendrobium officinale Polysaccharides?DOP?is the main active ingredient of Dendrobium officinale which can be used in immunomodulation and tumor treatment.Whether DOP has a protective effect on cisplatin-induced reproductive damage is not explored.Objective:To study effects of the prevention,protection DOP on reproductive damage,and it will provide an experimental basis for the protect and therapeutic application of DOP for reproductive damage.Method:In this study,six-week-old male Kunming mice were used to establish a reproductive damage model with CDDP.The effects of different doses of DOP on reproductive damage during a spermatogenesis cycle were studies.Furthermore,DOP was intragastrically administered at different time before and after cisplatin treatment to study the effects on male reproductive damage induced by cisplatin chemotherapy.Based on the DOP dose-effect results,the preventive and the recovery effects of DOP treatment in model were evaluated.Mice were randomly divided equally into control group,DOP group,CDDP group and CDDP-DOP group.?1?DOP dose-effect analysisMice in the CDDP and CDDP-DOP group were intraperitoneally injected with2.5 mg·kg^-1·d^-11 CDDP for 5 days from day 0 at 9 am,The mice in the DOP group and the control group were intraperitoneally injected with equal volume of saline.Instead the mice in the DOP group and the CDDP-DOP group were intragastrically administered with 100 mg·kg^-1·d^-1,200 mg·kg^-1·d^-11 and 400 mg·kg^-1·d^-11 DOP for 35consecutive days from the 5^thh day,the mice in the control group and CDDP group were intragastrically administered with equal volume of saline for 35 days at 5 pm.The mice were sacrificed at 9 am following the completion of intragastric administration.?2?DOP recovery from reproductive damageCDDP group and CDDP-DOP group mice were intraperitoneally injected with2.5 mg·kg^-1·d^-11 CDDP for 5 days,and mice in the DOP group and control group were intraperitoneally injected with equal volume of saline,the injection time was 9 am.On the next day after the establishment of the CDDP model,the DOP group and the CDDP-DOP group were continuously intragastrically administered with 200 mg·kg^-1·d^-11 DOP,the control group and the CDDP group mice were intragastrically administered with an equal volume of saline at 5pm.The mice in each group were sacrificed at 9 am at the 0^thh day,7^thh day,14^thh day,21^thh day,28^thh day and 35^thh day after DOP treatment.?3?DOP prevention of reproductive damageFrom the 0^thh day,mice in the DOP group and CDDP-DOP group were intragastrically administered with 200 mg·kg^-1·d^-11 DOP for 7 days and 14 days.The control group and the CDDP group mice were continuously intragastrically administered with equal volume of saline.On the following day after intragastric administration,mice in the CDDP group and CDDP-DOP group were intraperitoneally injected with 2.5 mg·kg^-1·d^-11 CDDP for 5 days at 9 am,and mice in the control group and DOP group were intraperitoneally injected with equal volume of saline.After the mice were intraperitoneally injected,they were naturally recovered.After the mice were injected intraperitoneally,they were naturally recovered for 17 days and 35 days,and were sacrificed at the next day 9 am.The testicular and epididymal index,the level of oxidative damage in testicular tissue,the number of sperm and sperm quality,and observed the histopathology of testicular tissue in each group of mice were analyzed.Result:?1?DOP dose-effect analysisCompared with mice in the control group,testicular index,epididymal index,the number of sperm and sperm quality were not significantly affected in mice which intragastrically administered with different dose of DOP for 35 days,and there was no significant change in testicular tissue histopathology.The anti-oxidation level of testis tissue in the DOP low-dose group change was low,but The antioxidant capacity of testis was enhanced,especially in the DOP medium and high dose groups.The main manifestations were SOD,GPx,CAT enzyme activity enhanced,GSH content increased,the MDA content after intragastrically administered with 3 different doses of DOP remained unchanged.Compared with mice in the control group and DOP group,testicular and epididymal index were significantly decreased in the CDDP group,Severe oxidative damage in mouse testis,testicular histopathology observed severe damage to testicular tissue in cisplatin group mice,injection of cisplatin led to a decrease in the number of sperm,and a decrease in the quality of sperm.In CDDP-DOP group mice,with the increase of the continuous intragastric administration dose of DOP,the number of spermatogenic cells,the number of newborn spermatozoa and the number of stromal cells gradually increased in testicular tissue at various stages,the number of sperm gradually increased,the sperm quality gradually improved,and the degree of oxidative damage of the testicular tissue gradually decreased.?2?DOP recovery from reproductive damageThere were no significant changes in testicular index,epididymal index,the number of sperm,sperm quality and testicular tissue histopathology in the mice treated with DOP for 35 days.Compared with mice in the CDDP group,Testicular tissue and sperm damage decreased significantly in the CDDP-DOP group mice,and the speed of damage recovery rate was significantly improved.?3?DOP prevention of reproductive damageThere was no significant effect on the testicular index,epididymal index,the number of sperm and sperm quality in mice that intragastrically administered with DOP continuously,there was no significant change in testicular tissue histopathology.The CDDP-DOP group mice were compared with the CDDP group mice,the number of spermatogenic cells and newborn sperm during each period increased,and the number of leydig cells increased,the number of sperm was increased,and sperm quality was improved.The longer the time of using DOP for prevention,the lighter the testis and sperm were damaged by CDDP.Conclusion:?1?DOP can effectively prevent and reduce the decrease of sperm number,sperm quality,testicular tissue oxidative damage and histopathological damage induced by CDDP injection.?2?DOP can promote the recovery of reproductive damage.?3?The protective effect of DOP on mouse reproductive system is time-dependent and dose-dependent.