Preventive and therapeutic effect of imatinib mesylate on radiation-induced lung injury mice and its influence on the oxidative stress and transforming growth factor-β1 expression in mice_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

 LIU Wenxiu ¹ , YANG Juan ¹ , CAO Bo ¹ ,  GAO Yuan ²

1. Department of Radiology, Affiliated Hospital of Yan’an University, Yan’an, Shanxi 716000, P. R. China;
2. Department of pulmonary diseases, Yan’an People’s Hospital, Yan’an, Shaanxi, 716000, P. R. China;

Corresponding author：

GAO Yuan, Email: 10272006@qq.com

Keywords：

Imatinib mesylate; Radiation-induced lung injury; Transforming growth factor-β ₁

DOI：

10.7507/1671-6205.201703027

Video：

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Objective To investigate the effect of imatinib mesylate on radiation-induced lung injury mice and its influence on the oxidative stress and transforming growth factor-β1 (TGF-β1) expression in mice. Methods Forty-five C57BL/6 mice were divided into a treatment group, a control group and a model group. The treatment group and model group were given radiation of 18 Gy delivered in the thorax. After 4 h daily of the radiation, the treatment group received imatinib mesylate of 0.081 g/kg, while the other groups were given normal saline solution. The experiments were continued for 30 days. After the experiments, the lungs of mice were divided into 4 parts. The haematoxylin and eosin and immunohistochemical stain were prepared to observe the situation of pathology and TGF-β1. The lung homogenate was prepared and the levels of superoxide dismutase (SOD), malondialdehyde (MDA), total antioxidant capacity (T-Aoc) and glutathione peroxidase (GSH-PX) were detected. Results The levels of GSH-PX, T-Aoc and SOD were (173.15±12.21) U, (119.33±11.06) U/mgprot and (1.73±0.33) nmol/mgprot in the treatment group, significantly higher than the control group, while the levels of MDA was (0.68±0.08) nmol/mgprot, significantly lower than the control group (P<0.05). The HE and immunohistochemical stain showed that there were mild alveolar inflammatory changes in the treatment group while such changes were serious in the model group. The scores of HE and immunohistochemical were 1.26±0.12 and 0.31±0.12 in the treatment group, significantly lower than those in the control group (P<0.05). Conclusion The imatinib mesylate can effectively ameliorate the oxidative stress and inhibite TGF-β1 expression in radiation-induced lung injury mice.

Citation： LIU Wenxiu, YANG Juan, CAO Bo, GAO Yuan. Preventive and therapeutic effect of imatinib mesylate on radiation-induced lung injury mice and its influence on the oxidative stress and transforming growth factor-β1 expression in mice. Chinese Journal of Respiratory and Critical Care Medicine, 2017, 16(5): 446-450. doi: 10.7507/1671-6205.201703027 Copy

1.	黎建绪, 郑雅梅, 胡晓燕, 等. 艾迪注射液对小鼠放射性肺损伤的防治作用. 医药导报, 2014, 33(2): 184-188.0.
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3.	Son Y, Lee HJ, Rho JK, et al. The ameliorative effect of silibinin against radiation-induced lung injury: protection of normal tissue without decreasing therapeutic efficacy in lung cancer. BMC Pulm Med. 2015, 15: 68.
4.	Fang XM, Hu CH, Hu XY, et al. An Appreciation for the Rabbit Ladderlike Modeling of Radiation-induced Lung Injury with High-energy X-Ray. Chin Med J (Engl). 2015, 128(12): 1636-1642.
5.	Malaviya R, Gow AJ, Francis M, et al. Radiation-induced lung injury and inflammation in mice: role of inducible nitric oxide synthase and surfactant protein D. Toxicol Sci. 2015, 144(1): 27-38.
6.	Elias MH, Bada AA, Azlan H, et al. BCＲ-ABL kinase domain mutations, including 2 novel mutations inimatinib resistant Malaysian chronic myeloid leukemia patients-Frequency and clinical Outcome. Leuk Res, 2014, 38(4): 454-459.
7.	Mathisen MS, Kantarjian HM, Cortes J, et al. Practical issues surrounding the explosion of tyrosine kinase inhibitors for the management of chronic myeloid leukemia. Blood Rev, 2014, 28(5): 179-187.
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9.	Jiao J, Gai QY, Zhang L, et al. High-speed homogenization coupled with microwave-assisted extraction followed by liquid chromatography-tandem mass spectrometry for the direct determination of alkaloids and flavonoids in fresh Isatis tinctoria L. hairy root cultures. Anal Bioanal Chem. 2015, 407(16): 4841-4848.
10.	Carter CL, Jones JW, Barrow K, et al. A MALDI-MSI Approach to the Characterization of Radiation-Induced Lung Injury and Medical Countermeasure Development.Health Phys. 2015, 109(5): 466-478.
11.	Giridhar P, Mallick S, Rath GK, et al. Radiation induced lung injury: prediction, assessment and management. Asian Pac J Cancer Prev. 2015, 16(7): 2613-2617.
12.	Santyr G, Fox M, Thind K, et al. Anatomical, functional and metabolic imaging of radiation-induced lung injury using hyperpolarized MRI. NMR Biomed. 2014, 27(12): 1515-1524.
13.	Murigi FN, Mohindra P, Hung C, et al. Dose Optimization Study of AEOL 10150 as a Mitigator of Radiation-Induced Lung Injury in CBA/J Mice. Radiat Res. 2015, 184(4): 422-432. doi: 10.1667/RR14110.1.
14.	Huang Y, Liu W, Liu H, et al. Grape seed pro-anthocyanidins ameliorates radiation-induced lung injury. J Cell Mol Med. 2014, 18(7): 1267-1277.
15.	Zhang J, Li B, Ding X, et al. Genetic variants in inducible nitric oxide synthase gene are associated with the risk of radiation-induced lung injury in lung cancer patients receiving definitive thoracic radiation. Radiother Oncol. 2014, 111(2): 194-198.
16.	Yu J, Yuan X, Liu Y, et al. Delayed Administration of WP1066, an STAT3 Inhibitor, Ameliorates Radiation-Induced Lung Injury in Mice. Lung. 2016, 194(1): 67-74.
17.	Zhao DY, Qu HJ, Guo JM, et al. Protective Effects of Myrtol Standardized Against Radiation-Induced Lung Injury. Cell Physiol Biochem. 2016, 38(2): 619-634.
18.	Kralj E, Zakelj S, Trontelj J, et al. Absorption and elimiation of imatinib through the rat intestine in vitro. Int J Pharm, 2014, 460(1/2): 144-149.
19.	Quinta’s-Cardama A, Jabbour EJ. Considerations for early switch to nilotinib or dasatinib in patients with chronic myeloid leukemia with inadequate response to first-line imatinib. Leuk Res, 2013, 37(5): 487-495.
20.	Liu Y, Tan D, Tong C, et al. Blueberry anthocyanins ameliorate radiation-induced lung injury through the protein kinase RNA-activated pathway. Chem Biol Interact. 2015, 242:363-371.

1. 黎建绪, 郑雅梅, 胡晓燕, 等. 艾迪注射液对小鼠放射性肺损伤的防治作用. 医药导报, 2014, 33(2): 184-188.0.
2. Li X, Xu G, Qiao T, et al. Effects of CpG oligodeoxynucleotide 1826 on acute radiation-induced lung injury in mice. Biol Res. 2016, 49(1): 8.
3. Son Y, Lee HJ, Rho JK, et al. The ameliorative effect of silibinin against radiation-induced lung injury: protection of normal tissue without decreasing therapeutic efficacy in lung cancer. BMC Pulm Med. 2015, 15: 68.
4. Fang XM, Hu CH, Hu XY, et al. An Appreciation for the Rabbit Ladderlike Modeling of Radiation-induced Lung Injury with High-energy X-Ray. Chin Med J (Engl). 2015, 128(12): 1636-1642.
5. Malaviya R, Gow AJ, Francis M, et al. Radiation-induced lung injury and inflammation in mice: role of inducible nitric oxide synthase and surfactant protein D. Toxicol Sci. 2015, 144(1): 27-38.
6. Elias MH, Bada AA, Azlan H, et al. BCＲ-ABL kinase domain mutations, including 2 novel mutations inimatinib resistant Malaysian chronic myeloid leukemia patients-Frequency and clinical Outcome. Leuk Res, 2014, 38(4): 454-459.
7. Mathisen MS, Kantarjian HM, Cortes J, et al. Practical issues surrounding the explosion of tyrosine kinase inhibitors for the management of chronic myeloid leukemia. Blood Rev, 2014, 28(5): 179-187.
8. 孙敬方. 动物实验方法学. 北京: 人民卫生出版社, 2001, 198-201.
9. Jiao J, Gai QY, Zhang L, et al. High-speed homogenization coupled with microwave-assisted extraction followed by liquid chromatography-tandem mass spectrometry for the direct determination of alkaloids and flavonoids in fresh Isatis tinctoria L. hairy root cultures. Anal Bioanal Chem. 2015, 407(16): 4841-4848.
10. Carter CL, Jones JW, Barrow K, et al. A MALDI-MSI Approach to the Characterization of Radiation-Induced Lung Injury and Medical Countermeasure Development.Health Phys. 2015, 109(5): 466-478.
11. Giridhar P, Mallick S, Rath GK, et al. Radiation induced lung injury: prediction, assessment and management. Asian Pac J Cancer Prev. 2015, 16(7): 2613-2617.
12. Santyr G, Fox M, Thind K, et al. Anatomical, functional and metabolic imaging of radiation-induced lung injury using hyperpolarized MRI. NMR Biomed. 2014, 27(12): 1515-1524.
13. Murigi FN, Mohindra P, Hung C, et al. Dose Optimization Study of AEOL 10150 as a Mitigator of Radiation-Induced Lung Injury in CBA/J Mice. Radiat Res. 2015, 184(4): 422-432. doi: 10.1667/RR14110.1.
14. Huang Y, Liu W, Liu H, et al. Grape seed pro-anthocyanidins ameliorates radiation-induced lung injury. J Cell Mol Med. 2014, 18(7): 1267-1277.
15. Zhang J, Li B, Ding X, et al. Genetic variants in inducible nitric oxide synthase gene are associated with the risk of radiation-induced lung injury in lung cancer patients receiving definitive thoracic radiation. Radiother Oncol. 2014, 111(2): 194-198.
16. Yu J, Yuan X, Liu Y, et al. Delayed Administration of WP1066, an STAT3 Inhibitor, Ameliorates Radiation-Induced Lung Injury in Mice. Lung. 2016, 194(1): 67-74.
17. Zhao DY, Qu HJ, Guo JM, et al. Protective Effects of Myrtol Standardized Against Radiation-Induced Lung Injury. Cell Physiol Biochem. 2016, 38(2): 619-634.
18. Kralj E, Zakelj S, Trontelj J, et al. Absorption and elimiation of imatinib through the rat intestine in vitro. Int J Pharm, 2014, 460(1/2): 144-149.
19. Quinta’s-Cardama A, Jabbour EJ. Considerations for early switch to nilotinib or dasatinib in patients with chronic myeloid leukemia with inadequate response to first-line imatinib. Leuk Res, 2013, 37(5): 487-495.
20. Liu Y, Tan D, Tong C, et al. Blueberry anthocyanins ameliorate radiation-induced lung injury through the protein kinase RNA-activated pathway. Chem Biol Interact. 2015, 242:363-371.

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