Study On The Intervention Of Proanthocyanidins On Reproductive System Damage In Male Wistar Rats Caused By Cadmium

Cadmium（Cdmium,Cd）is a heavy metal widely present in the environment.Studies have shown that the male reproductive system is extremely sensitive to Cd and the reproductive dysfunction in male animal may caused by low concentration of Cd in testis,testicular toxicity induced by Cd is due to oxidative stress and inflammatory effects.Proanthocyanidins（PAs）,also known as condensed tannins,are a class of flavonoids found in the nuclei,pericarp,or seeds of various plants widely found in nature.PAs is considered as an antioxidant molecule that has a very potent inhibitory effect on oxidative stress and cytoprotection and can remove free radicals in the body effectively.The purpose of this study was to evaluate the potential chemoprotective effect of proanthocyanidins（PAs）against cadmium（Cd）-induced oxidative damage of testes via Nrf2-Keap1 single path in rats.A total 32 male adult Wistar rats were individed into 4 equel groups randomly.GroupⅠwas served as the control group（0.5 ml physiological saline/Kg/d）.GroupsⅡ-Ⅳwere treated with cadmium chloride（CdCl₂）（5 mg/kg/day,orally）,PAs（100 mg/kg/day,orally）,and CdCl₂+PAs（CdCl₂ was given 120 min after PAs administration）for a month,respectively.At the end of the trial,the testis and epididymis organs coefficients were calculated,then the sperm quality and the levels of anti-oxidation of testis were measured.qPCR and Western blot were used to detect the changes of mRNA and protein expressions of Nrf2 and its related genes,respectively.The results showed:（1）Cd induced body growth inhibition and reproductive system damage that was demonstrated by the decrease of testicular organ coefficient,semen quality,serum testosterone level and a series of serious alterations in histology.（2）PAs could inhibit the genital injury caused by Cd exposure and improve the quality of semen,the histopathological and ultrastructural changes showed that PAs antagonize testicular toxicity induced by Cd.（3）PAs could inhibit the changes of antioxidant status induced by Cd exposure,decrease the content of MDA and H₂O₂,increase the content of GSH and increase the activity of antioxidant enzymes CAT,T-SOD and GSH-Px in rats testis.（4）PAs could protect the reproductive system damage of Wistar rats by activating the Nrf2-Keap1 signaling pathway to increase Nrf2 and its downstream genes HO-1,γ-GCS,GSH-Px,NQO1 mRNA and protein expressions that could resist oxidative stress induced by Cd.In conclusion,PAs exhibit a significant potential chemopreventive effect against Cd-induced testes oxidative damage,possibly through the modification of Nrf2-Keap1 signal path in rats.