ABSTRACT
@#Objective To investigate the effect of acute exposure to cadmium combined with bacitracin on the endoplasmic reticulum stress (ERS) in testes and ovaries of rats and its regulation by nuclear factor erythroid-2-related factor 2 (Nrf2). Methods According to the 4×2 factorial design model, 48 specific pathogen free adult SD rats were divided into four groups: the control group and the low-, medium- and high- dose cadmium chloride exposure groups. Each group was further divided into with- or without bacitracin combined subgroup. There were six rats in each subgroup with 3 males and 3 females. The low-, medium- and high- dose groups were intraperitoneally injected with 5, 10, 20 mg/kg body weight of cadmium chloride solution, respectively. The control group was intraperitoneally injected with the same amount of 0.9% sodium chloride solution. Among them, rats in the bacitracin combined subgroup were given a one-time intraperitoneal injection of bacitracin at a dose of 20 mg/kg body weight two hours before cadmium chloride exposure. After 48 hours, the rats were sacrificed. The mRNA expression of glucose regulated protein78 kD (Grp78), protein kinase R-like endoplasmic reticulum kinase (Perk), Nrf2 in testes and ovaries of rats was determined using quantitative real-time polymerase chain reaction. The protein expression of GRP78, PERK, NRF2 was determined using Western blotting. Results The mRNA expression of Grp78, Perk, Nrf2 and the protein expression of GRP78, PERK, NRF2 in testes and ovaries of rats in the no bacitracin combined subgroups of the three dose groups showed different degrees of up-regulated changes compared with the no bacitracin combined subgroup of the control group (all P<0.05). Among them, the expression of the three kinds of mRNAs and proteins in the testes and ovaries of rats in the no bacitracin combined subgroups of the high-dose group was up-regulated (all P<0.05), and most of them were higher than those in the no bacitracin combined subgroups of the low- and medium-dose groups (all P<0.05). The expression of most of the three kinds of mRNAs and proteins in testes of rats showed different degrees of down-regulated changes (all P<0.05), but the expression of the three kinds of mRNAs and proteins showed different degrees of up-regulated changes in ovaries (all P<0.05) in the bacitracin combined subgroups of the three doses groups than that in the bacitracin combined subgroups of the control group, and especially in the bacitracin combined subgroups of the high-dose subgroup. The expression of the three kinds of mRNAs and proteins in testes and ovaries of rats in the bacitracin combined subgroups of the three doses groups showed different degrees of changes (all P<0.05) compared with the no bacitracin combined subgroup in the same group, and the expression in the bacitracin combined subgroups of the medium- and high-dose groups showed mainly down-regulated changes (all P<0.05). Conclusion Acute exposure to cadmium can induce different degrees of ERS, activate PERK/NRF2 signaling pathway, and improve the toxicity to testis and ovary. Bacitracin can inhibit cadmium-induced ERS, thereby inhibiting the activation of PERK/NRF2 signaling pathway, and enhancing the synergistic effect of cadmium on testis and ovary toxicity. The higher the exposure dose of cadmium, the more obvious the inhibitory effect.