Protective effect of curcumin on radiation-inducedpancreatic exocrine cell damage
LIU Xianrong, HE Liyan, LU Xianzhou
RADIATION PROTECTION. 2019, 39(2):
157-167.
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In order to elucidate the stress response and energy metabolism of pancreatic exocrine cells induced by ionizing radiation, and to explore the role of curcumin in pancreatic exocrine cell radiation injury and its mechanism,the experiment of Rat pancreatic exocrine cells (AR42J) were established. The rats were divided into experimental group and control group. The two groups were divided into five subgroups of A/B/C/D/E, which were treated with 0, 2, 4, 8 and 16 μM curcumin, repectively. The experimental group was given a one-time high-dose X-ray irradiation (6 Gy), simulating acute radiation damage events. The expression of PARP, BCL-2, stress and energy metabolism related factors HIF-1ɑ, LDHA and PDH were detected by Wensten-blot. The cell viability was detected by MTT assay, Fluorescence detection of cell ATP and ROS production. The experimental results were further validated by in vivo experiments. 24 clean-grade rats were randomly divided into control group, simple drug-added group, simple irradiation group, irradiation + dosing group. Rats in each group were exposed to 12 Gy X-ray or simulated irradiation. The rats were killed 24 hours after irradiation, and the pancreatic tissue was dissected. The expression of energy metabolism related proteins was examined by Wensten-blot method. The results demonstrate: 1) Compared with the control group, the expression of PARP was increased and the BCL-2 protein was slightly down-regulated after 24 hours of irradiation. Meanwhile, the decrease of mitochondrial membrane potential (ΔΨm) was observed which indicated mitochondria damage. 2) The expression of HIF-1α was significantly increased by irradiation, and LDHA, the key factor of glycolysis was significantly increased and PDH expression was down-regulated. 3) MTT assay showed a decrease in cell proliferation and the production of ROS was increased by microplate reader. 4) Silence HIF-1α by RNA technology had eliminated irradiation-induced energy metabolism transformation partly. In the experimental group, the increased expression of HIF-1α and LDHA was reversed by curcumin treatment, PDH was partially restored, the free radical scavenging was effectively removed, and the proliferation of cells and the ATP production were increased. 5) The animal experiments have got the same results. The expression of HIF-1α is up-regulated by ionizing radiation stress in pancreatic exocrine cells, which leads to the change of energy metabolism as the enhancement of glycolysis pathway and the inhibition of aerobic oxidation of mitochondria. Curcumin reduces the energy metabolism disorder induced by radiation by down-regulating HIF-1α, and effectively scavenges oxygen free radicals and protects mitochondria, thus exerting its protective effect on pancreatic exocrine cells.
