Effects of neutron radiation on Nrf2‑regulated antioxidant defense systems in rat lens

Abstract

Accumulating evidence suggests that ionizing radiation (IR)-induced cataract may be associated with oxidative stress. Nuclear factor erythroid 2-related factor 2 (Nrf2) serves as a master regulator of the antioxidant defense system against oxidative stress. The present study aimed to investigate the effects of different doses of neutron radiation on the Nrf2-reegulated antioxidant defense system in rat lens and assess the status of oxidative stress. A total of 24 SD rats were randomly divided into the following four groups: i) Control group; iis) 0.4 Sv group; iii) 1.2 Sv group; and iv) 3.6 Sv group. The rats were sacrificed 7 days after radiation and lenses were dissected for histological, biochemical (malondialdehyde, glutathione and superoxide dismutase) and western blot (Nrf2, glutamate-cysteine ligase catalytic subunit and heme oxygenase 1) analyses. The morphological features of the lenses remained intact in the 0.4 Sv, 1.2 Sv and control groups, whilst the lenses in the 3.6 Sv group exhibited injuries. Results from the TUNEL assay demonstrated apparent apoptosis in lens epithelial cells following 3.6 Sv neutron radiation whereas sparse apoptosis was observed following 0.4 Sv and 1.2 Sv radiation. Malondialdehyde levels were reduced in the 0.4 Sv and 1.2 Sv groups but increased in the 3.6 Sv group, compared with those in the control group. Conversely, glutathione expression and the activity of superoxide dismutase were higher in the 0.4 Sv and 1.2 Sv groups, but lower in the 3.6 Sv group, compared with those in the control group. In addition, the total and nuclear protein levels of Nrf2 were increased following neutron radiation compared with those in the control group, though the Nrf2 protein levels decreased in the 3.6 Sv group compared with those in the 1.2 Sv group. The levels of glutamate-cysteine ligase catalytic subunit and heme oxygenase 1, downstream antioxidant enzymes of Nrf2, demonstrated the same profile as that in Nrf2. Taken together, the results of the present study suggest that neutron radiation affects Nrf2-regulated antioxidant systems in a two-stage process. Namely, the induction phase for low-dose radiation and regression phase for high-dose radiation. Therefore, it was hypothesized that activation and enhancement of the Nrf2-regulated antioxidant system may be useful in preventing or delaying IR-induced cataract, which may be extended even for other diseases associated with oxidative stress.

Ferulic Acid Protects Human Lens Epithelial Cells against Ionizing Radiation-Induced Oxidative Damage by Activating Nrf2/HO-1 Signal Pathway

“…The lens is one of the most radiosensitive tissues in the human body, and it is known that ionizing radiation can induce cataract, which is ranked second among occupational diseases associated with radiation in China [ 27 ]. Our previous study showed that IR-induced cataract is related to the incapacity of Nrf2 antioxidative systems in the lens [ 13 ]. Enhanced oxidative stress and decreased antioxidant defensive capacity are thought to be the two main contributors to the pathogenesis of cataract [ 28 ].…”

“…Nrf2 signal pathway is highly associated with oxidative stress in the lens [ 13 , 42 ]. Nrf2 has been proved to be maintained at a low level through 26S proteasome-mediated degradation and Keap1-mediated ubiquitylation.…”

“…Nuclear factor erythroid 2-related factor 2 (Nrf2) is one of the most important transcription factors that control the transcription of many antioxidant genes, such as glutathione reductase (GR), superoxide dismutase (SOD), GSH-Px (GPx), catalase (CAT), glutamate-cysteine ligase (GCL), and heme oxygenase-1 (HO-1), to combat ROS and boost cell survival [ 11 , 12 ]. Our previous study has shown that IR-induced cataract is related to the incapacity of Nrf2 antioxidative systems [ 13 ]. Taken together, these findings suggest that Nrf2 inducers may serve as potential therapeutic agents for preventing or alleviating IR-induced cataract.…”

Protective effects of ferulic acid against ionizing radiation-induced oxidative damage in rat lens through activating Nrf2 signal pathway

“…They received a single dose of 10 Gy whole-body γ-radiation at a rate of 1.38 Gy/min. The γ-radiation dose was determined based on our previous study about the effect of neutron radiation on rat lens and Nrf2 signal pathway, and the biological effect of 3.6 Sv neutron radiation is equivalent to 10 Gy γ-radiation [12] . The FA dose was determined according to previous literatures [15][16] .…”

“…One of the most crucial defenses against oxidative stress is the antioxidative system controlled by nuclear factor erythroid-2 related factor (Nrf2) [11] . In a previous study, we discovered that IR-induced cataract is associated with a dysfunctional Nrf2 antioxidative system in the lens [12] . Together, these suggest that activating the Nrf2 signal pathway might be a way to attenuate IR-induced lens injury.…”