Feedback regulation of Nrf2 on cadmium chloride-induced endoplasmic reticulum stress in testicles and ovaries of rats
Objective To investigate the feedback regulatory effects of nuclear factor erythroid 2-related factor 2(Nrf2)on cad-mium chloride(CdCl2)-induced endoplasmic reticulum stress in the testicles and ovaries of rats.Methods Forty-eight Sprague-Daw-ley rats were randomly divided into eight groups(six rats in each group)according to the cadmium chloride exposure dose and whether to administer tert-butylhydroquinone(tBHQ):control group(intraperitoneal injection of 0.9%normal saline);low-dose,medium-dose,and high-dose CdCl2 groups(intraperitoneal injected of CdCl2 solution at 1.14,2.28,and 4.56 mg/kg,respectively);tBHQ group(intraperitoneal injection of 20 mg/kg tBHQ solution);and tBHQ+low-dose,tBHQ+medium-dose,and tBHQ+high-dose CdCl2 groups(pretreatment with 20 mg/kg tBHQ solution 120 minutes before intraperitoneal injection of 1.14,2.28,and 4.56 mg/kg CdCl2 solution,respectively).After 48 hours of exposure,the rats were sacrificed to collect the testicles and ovaries,and the mRNA and protein expression levels of 78 kDa glucose-regulated protein(Bip),PKR-like endoplasmic reticulum kinase(PERK),Nrf2 was de-termined by RT-PCR and Western blot.Results Compared with tBHQ group,the expression of Nrf2 mRNA and protein in the testi-cles in the tBHQ+medium-dose CdCl2 group was significantly increased(F were 144.47 and 302.88,respectively,P<0.05);the ex-pression of Nrf2 mRNA and protein in the ovaries in the tBHQ+low-dose,medium-dose,and high-dose CdCl2 groups was all signifi-cantly increased(F were 55.97 and 80.08,respectively,P<0.05).Compared with the same dose of CdCl2 group,the tBHQ+medi-um-dose CdCl2 group showed significantly increased expression of Nrf2 protein in the testicles(F= 74.66,P<0.05),with no signifi-cant differences in the expression of Bip and PERK in the testicles;the tBHQ+high-dose CdCl2 group showed a significant increase in the expression of Nrf2 protein in the ovaries(F=30.58,P<0.05)and varying degrees of reductions in the expression of Bip mRNA and protein(F were 33.13,25.28,and 30.24,respectively,P<0.05),and PERK mRNA in the ovaries,and the expression of Nrf2 pro-tein was negatively correlated with the expression of Bip mRNA and PERK mRNA in the ovaries(r were-0.783 and-0.817,respec-tively,P<0.05);the tBHQ+high-dose CdCl2 group showed significant decreases in the mRNA expression of PERK and Nrf2,and the protein expression of Bip,PERK,and Nrf2 in the testicles(F were 19.73,53.63,25.28,99.98 and 74.66,respectively,P<0.05).Conclusion Pretreatment with tBHQ can induce varying degrees of Nrf2 expression in the testicles and ovaries of rats exposed to dif-ferent doses of CdCl2.The up-regulation of Nrf2 expression in the ovaries of rats can reduce the level of endoplasmic reticulum stress through the PERK/Nrf2 pathway,thereby alleviating the damage of cadmium to the ovaries.
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