Pharmacological Approach for Prevention of Bleomycin-Induced Lung Injury
Abstract
Bleomycin is a chemotherapeutic medication commonly use in the treatment of Hodgkin's disease and germ cell tumors. Pulmonary fibrosis is major and dose limiting adverse effect of the drug. There is not currently any equal alternative approach or a medical agent for prevention of its pulmonary injury. We searched scientific databases in order to find investigational pharmacologic medicines in prevention of bleomycin-induced lung toxicity (BILI). Results revealed that some anti-inflammatory and antioxidant preparations such as statins, N-acetylcysteine (NAC), supplements (vitamin D3, L-arginine, selenium), and renin-angiotensin-aldosterone system (RASS) inhibitors might be effective in preclinical models of pulmonary toxicity mediated by bleomycin. However, we still need more in vivo studies and large human randomized clinical trials to confirm their benefits.
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2. Gerriets V, Kasi A. Bevacizumab. StatPearls [Internet]: StatPearls Publishing; 2022.
3. Reinert T, Baldotto CSdR, Nunes FAP, Scheliga AAdS. Bleomycin-induced lung injury. Journal of Cancer Research. 2013;2013.
4. Schwartz DR, Homanics GE, Hoyt DG, Klein E, Abernethy J, Lazo JS. The neutral cysteine protease bleomycin hydrolase is essential for epidermal integrity and bleomycin resistance. Proc Natl Acad Sci U S A. 1999;96(8):4680-5.
5. Chen J, Chen Y, He Q. Action of bleomycin is affected by bleomycin hydrolase but not by caveolin-1. Int J Oncol. 2012;41(6):2245-52.
6. Camus P. Interstitial lung disease from drugs, biologics, and radiation. Interstitial Lung Disease 5th ed Shelton, CT: People’s Medical Publishing House. 2011;637.
7. O’sullivan J, Huddart R, Norman A, Nicholls J, Dearnaley D, Horwich A. Predicting the risk of bleomycin lung toxicity in patients with germ-cell tumours. Ann Oncol. 2003;14(1):91-6.
8. White DA, Stover DE. Severe bleomycin-induced pneumonitis: clinical features and response to corticosteroids. Chest. 1984;86(5):723-8.
9. Einhorn LH, Williams SD, Loehrer PJ, et al. Evaluation of optimal duration of chemotherapy in favorable-prognosis disseminated germ cell tumors: a Southeastern Cancer Study Group protocol. J Clin Oncol. 1989;7(3):387-91.
10. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Eur Heart J. 2020;41(1):111-88.
11. Rabar S, Harker M, O’Flynn N, Wierzbicki AS. Lipid modification and cardiovascular risk assessment for the primary and secondary prevention of cardiovascular disease: summary of updated NICE guidance. BMJ. 2014;349.
12. Beltowski J. Statins and modulation of oxidative stress. Toxicol Mech Methods. 2005;15(2):61-92.
13. Sørensen AL, Hasselbalch HC, Nielsen CH, Poulsen HE, Ellervik C. Statin treatment, oxidative stress and inflammation in a Danish population. Redox Biol. 2019;21:101088.
14. Tulek B, Kiyan E, Kiyici A, Toy H, Bariskaner H, Suerdem M. Effects of simvastatin on bleomycin-induced pulmonary fibrosis in female rats. Biol Res. 2012;45(4):345-50.
15. Zhu B, Ma AQ, Yang L, Dang XM. Atorvastatin attenuates bleomycin-induced pulmonary fibrosis via suppressing iNOS expression and the CTGF (CCN2)/ERK signaling pathway. Int J Mol Sci. 2013;14(12):24476-91.
16. Liu C, Kuo M, Wu B, et al. NO-releasing xanthine KMUP-1 bonded by simvastatin attenuates bleomycin-induced lung inflammation and delayed fibrosis. Pulm Pharmacol Ther. 2014;27(1):17-28.
17. Fountain JH, Lappin SL. Physiology, Renin Angiotensin System. 2022 Jun 18. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–.
18. Nehme A, Zouein FA, Deris Zayeri Z, Zibara K. An update on the tissue renin angiotensin system and its role in physiology and pathology. J Cardiovasc Dev Dis. 2019;6(2):14.
19. Pacurari M, Kafoury R, Tchounwou PB, Ndebele K. The renin-angiotensin-aldosterone system in vascular inflammation and remodeling. Int J Inflam. 2014;2014:689360.
20. Gupta D, Kumar A, Mandloi A, Shenoy V. Renin angiotensin aldosterone system in pulmonary fibrosis: Pathogenesis to therapeutic possibilities. Pharmacol Res. 2021;174:105924.
21. Tanaka J, Tajima S, Asakawa K, et al. Preventive effect of irbesartan on bleomycin-induced lung injury in mice. Respir Investig. 2013;51(2):76-83.
22. Hara R, Onizuka M, Shiraiwa S, et al. The role of hypertension and renin-angiotensin-aldosterone system inhibitors in bleomycin-induced lung injury. Clinical Lymphoma Myeloma and Leukemia. 2021;21(4):e321-e7.
23. Šalamon Š, Kramar B, Marolt TP, Poljšak B, Milisav I. Medical and dietary uses of N-acetylcysteine. Antioxidants. 2019;8(5):111.
24. Cortijo J, Cerda-Nicolas M, Serrano A, et al. Attenuation by oral N-acetylcysteine of bleomycin-induced lung injury in rats. Eur Respir J. 2001;17(6):1228-35.
25. Serrano-Mollar A, Closa D, Prats N, et al. In vivo antioxidant treatment protects against bleomycin-induced lung damage in rats. Brit J Pharmacol. 2003;138(6):1037.
26. Yildirim Z, Kotuk M, Iraz M, et al. Attenuation of bleomycin-induced lung fibrosis by oral sulfhydryl containing antioxidants in rats: erdosteine and N-acetylcysteine. Pulm Pharmacol Ther. 2005;18(5):367-73.
27. Teixeira KC, Soares FS, Rocha LG, et al. Attenuation of bleomycin-induced lung injury and oxidative stress by N-acetylcysteine plus deferoxamine. Pulm Pharmacol Ther. 2008;21(2):309-16.
28. Brigelius-Flohé R. Selenium in human health and disease: An overview. Selenium. 2018:3-26.
29. Zhang J, Wang X, Xu T. Elemental selenium at nano size (Nano-Se) as a potential chemopreventive agent with reduced risk of selenium toxicity: comparison with se-methylselenocysteine in mice. Toxicol Sci. 2008;101(1):22-31.
30. Huang Z, Rose AH, Hoffmann PR. The role of selenium in inflammation and immunity: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal. 2012;16(7):705-43.
31. Shahabi R, Anissian A, Javadmoosavi SA, Nasirinezhad F. Protective and anti-inflammatory effect of selenium nano-particles against bleomycin-induced pulmonary injury in male rats. Drug Chem Toxicol. 2021;44(1):92-100.
32. Slatopolsky E, Finch J, Ritter C, Takahashi F. Effects of 19-nor-1, 25 (OH) 2D2, a new analogue of calcitriol, on secondary hyperparathyroidism in uremic rats. Am J Kidney Dis. 1998;32(4):S40-S7.
33. Coyne D, Acharya M, Qiu P, et al. Paricalcitol capsule for the treatment of secondary hyperparathyroidism in stages 3 and 4 CKD. Am J Kidney Dis. 2006;47(2):263-76.
34. Chang J, Nie H, Ge X, et al. Vitamin D suppresses bleomycin-induced pulmonary fibrosis by targeting the local renin–angiotensin system in the lung. Sci Rep. 2021;11(1):1-12.
35. Palmer RM, Ashton D, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 1988;333(6174):664-6.
36. Tapiero H, Mathe G, Couvreur P, Tew KI. Arginine. Biomed Pharmacother. 2002;56(9):439-45.
37. Morris Jr SM. Arginine: beyond protein. Am J Clin Nutr. 2006;83(2):508S-12S.
38. Gokce N. L-arginine and hypertension. J Nutr. 2004;134(10):2807S-11S.
39. Gao L, Zhang JH, Chen XX, et al. Combination of L-Arginine and L-Norvaline protects against pulmonary fibrosis progression induced by bleomycin in mice. Biomed Pharmacother. 2019;113:108768.
40. Björk I, Lindahl U. Mechanism of the anticoagulant action of heparin. Mol Cell Biochem. 1982;48(3):161-82.
41. Gunther A, Lubke N, Ermert M, et al. Prevention of bleomycin-induced lung fibrosis by aerosolization of heparin or urokinase in rabbits. Am J Respir Crit Care Med. 2003;168(11):1358-65.
42. Franks ME, Macpherson GR, Figg WD. Thalidomide. Lancet. 2004;363(9423):1802-11.
43. Vargesson N. Thalidomide‐induced teratogenesis: History and mechanisms. Birth Defects Res C Embryo Today. 2015;105(2):140-56.
44. Tabata C, Tabata R, Kadokawa Y, et al. Thalidomide prevents bleomycin-induced pulmonary fibrosis in mice. J Immunol. 2007;179(1):708-14.
45. Yedinak KC, Lopez LM. Felodipine: a new dihydropyridine calcium-channel antagonist. DICP. 1991;25(11):1193-206.
46. Navadiya K, Tiwari S. Pharmacology, efficacy and safety of felodipine with a focus on hypertension and angina pectoris. Curr Drug Saf. 2015;10(3):194-201.
47. Tanaka K-i, Niino T, Ishihara T, et al. Protective and therapeutic effect of felodipine against bleomycin-induced pulmonary fibrosis in mice. Sci Rep. 2017;7(1):1-12.
48. Gillman P. Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Brit J Pharmacol. 2007;151(6):737-48.
49. Zaafan MA, Haridy AR, Abdelhamid AM. Amitriptyline attenuates bleomycin-induced pulmonary fibrosis: modulation of the expression of NF-κβ, iNOS, and Nrf2. Naunyn Schmiedebergs Arch Pharmacol. 2019;392(3):279-86.
50. Rodriguez BSQ, Correa R. Gemfibrozil. StatPearls [Internet]: StatPearls Publishing; 2022.
51. Mohammadi Y, Khodayar MJ, Hemmati A, Mansouri E. The preventive role of gemfibrozil on bleomycin-induced lung injury and fibrosis in rats. Jundishapur Journal of Natural Pharmaceutical Products. 2017;12(3 (Supp));e64314.
2. Gerriets V, Kasi A. Bevacizumab. StatPearls [Internet]: StatPearls Publishing; 2022.
3. Reinert T, Baldotto CSdR, Nunes FAP, Scheliga AAdS. Bleomycin-induced lung injury. Journal of Cancer Research. 2013;2013.
4. Schwartz DR, Homanics GE, Hoyt DG, Klein E, Abernethy J, Lazo JS. The neutral cysteine protease bleomycin hydrolase is essential for epidermal integrity and bleomycin resistance. Proc Natl Acad Sci U S A. 1999;96(8):4680-5.
5. Chen J, Chen Y, He Q. Action of bleomycin is affected by bleomycin hydrolase but not by caveolin-1. Int J Oncol. 2012;41(6):2245-52.
6. Camus P. Interstitial lung disease from drugs, biologics, and radiation. Interstitial Lung Disease 5th ed Shelton, CT: People’s Medical Publishing House. 2011;637.
7. O’sullivan J, Huddart R, Norman A, Nicholls J, Dearnaley D, Horwich A. Predicting the risk of bleomycin lung toxicity in patients with germ-cell tumours. Ann Oncol. 2003;14(1):91-6.
8. White DA, Stover DE. Severe bleomycin-induced pneumonitis: clinical features and response to corticosteroids. Chest. 1984;86(5):723-8.
9. Einhorn LH, Williams SD, Loehrer PJ, et al. Evaluation of optimal duration of chemotherapy in favorable-prognosis disseminated germ cell tumors: a Southeastern Cancer Study Group protocol. J Clin Oncol. 1989;7(3):387-91.
10. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Eur Heart J. 2020;41(1):111-88.
11. Rabar S, Harker M, O’Flynn N, Wierzbicki AS. Lipid modification and cardiovascular risk assessment for the primary and secondary prevention of cardiovascular disease: summary of updated NICE guidance. BMJ. 2014;349.
12. Beltowski J. Statins and modulation of oxidative stress. Toxicol Mech Methods. 2005;15(2):61-92.
13. Sørensen AL, Hasselbalch HC, Nielsen CH, Poulsen HE, Ellervik C. Statin treatment, oxidative stress and inflammation in a Danish population. Redox Biol. 2019;21:101088.
14. Tulek B, Kiyan E, Kiyici A, Toy H, Bariskaner H, Suerdem M. Effects of simvastatin on bleomycin-induced pulmonary fibrosis in female rats. Biol Res. 2012;45(4):345-50.
15. Zhu B, Ma AQ, Yang L, Dang XM. Atorvastatin attenuates bleomycin-induced pulmonary fibrosis via suppressing iNOS expression and the CTGF (CCN2)/ERK signaling pathway. Int J Mol Sci. 2013;14(12):24476-91.
16. Liu C, Kuo M, Wu B, et al. NO-releasing xanthine KMUP-1 bonded by simvastatin attenuates bleomycin-induced lung inflammation and delayed fibrosis. Pulm Pharmacol Ther. 2014;27(1):17-28.
17. Fountain JH, Lappin SL. Physiology, Renin Angiotensin System. 2022 Jun 18. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–.
18. Nehme A, Zouein FA, Deris Zayeri Z, Zibara K. An update on the tissue renin angiotensin system and its role in physiology and pathology. J Cardiovasc Dev Dis. 2019;6(2):14.
19. Pacurari M, Kafoury R, Tchounwou PB, Ndebele K. The renin-angiotensin-aldosterone system in vascular inflammation and remodeling. Int J Inflam. 2014;2014:689360.
20. Gupta D, Kumar A, Mandloi A, Shenoy V. Renin angiotensin aldosterone system in pulmonary fibrosis: Pathogenesis to therapeutic possibilities. Pharmacol Res. 2021;174:105924.
21. Tanaka J, Tajima S, Asakawa K, et al. Preventive effect of irbesartan on bleomycin-induced lung injury in mice. Respir Investig. 2013;51(2):76-83.
22. Hara R, Onizuka M, Shiraiwa S, et al. The role of hypertension and renin-angiotensin-aldosterone system inhibitors in bleomycin-induced lung injury. Clinical Lymphoma Myeloma and Leukemia. 2021;21(4):e321-e7.
23. Šalamon Š, Kramar B, Marolt TP, Poljšak B, Milisav I. Medical and dietary uses of N-acetylcysteine. Antioxidants. 2019;8(5):111.
24. Cortijo J, Cerda-Nicolas M, Serrano A, et al. Attenuation by oral N-acetylcysteine of bleomycin-induced lung injury in rats. Eur Respir J. 2001;17(6):1228-35.
25. Serrano-Mollar A, Closa D, Prats N, et al. In vivo antioxidant treatment protects against bleomycin-induced lung damage in rats. Brit J Pharmacol. 2003;138(6):1037.
26. Yildirim Z, Kotuk M, Iraz M, et al. Attenuation of bleomycin-induced lung fibrosis by oral sulfhydryl containing antioxidants in rats: erdosteine and N-acetylcysteine. Pulm Pharmacol Ther. 2005;18(5):367-73.
27. Teixeira KC, Soares FS, Rocha LG, et al. Attenuation of bleomycin-induced lung injury and oxidative stress by N-acetylcysteine plus deferoxamine. Pulm Pharmacol Ther. 2008;21(2):309-16.
28. Brigelius-Flohé R. Selenium in human health and disease: An overview. Selenium. 2018:3-26.
29. Zhang J, Wang X, Xu T. Elemental selenium at nano size (Nano-Se) as a potential chemopreventive agent with reduced risk of selenium toxicity: comparison with se-methylselenocysteine in mice. Toxicol Sci. 2008;101(1):22-31.
30. Huang Z, Rose AH, Hoffmann PR. The role of selenium in inflammation and immunity: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal. 2012;16(7):705-43.
31. Shahabi R, Anissian A, Javadmoosavi SA, Nasirinezhad F. Protective and anti-inflammatory effect of selenium nano-particles against bleomycin-induced pulmonary injury in male rats. Drug Chem Toxicol. 2021;44(1):92-100.
32. Slatopolsky E, Finch J, Ritter C, Takahashi F. Effects of 19-nor-1, 25 (OH) 2D2, a new analogue of calcitriol, on secondary hyperparathyroidism in uremic rats. Am J Kidney Dis. 1998;32(4):S40-S7.
33. Coyne D, Acharya M, Qiu P, et al. Paricalcitol capsule for the treatment of secondary hyperparathyroidism in stages 3 and 4 CKD. Am J Kidney Dis. 2006;47(2):263-76.
34. Chang J, Nie H, Ge X, et al. Vitamin D suppresses bleomycin-induced pulmonary fibrosis by targeting the local renin–angiotensin system in the lung. Sci Rep. 2021;11(1):1-12.
35. Palmer RM, Ashton D, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 1988;333(6174):664-6.
36. Tapiero H, Mathe G, Couvreur P, Tew KI. Arginine. Biomed Pharmacother. 2002;56(9):439-45.
37. Morris Jr SM. Arginine: beyond protein. Am J Clin Nutr. 2006;83(2):508S-12S.
38. Gokce N. L-arginine and hypertension. J Nutr. 2004;134(10):2807S-11S.
39. Gao L, Zhang JH, Chen XX, et al. Combination of L-Arginine and L-Norvaline protects against pulmonary fibrosis progression induced by bleomycin in mice. Biomed Pharmacother. 2019;113:108768.
40. Björk I, Lindahl U. Mechanism of the anticoagulant action of heparin. Mol Cell Biochem. 1982;48(3):161-82.
41. Gunther A, Lubke N, Ermert M, et al. Prevention of bleomycin-induced lung fibrosis by aerosolization of heparin or urokinase in rabbits. Am J Respir Crit Care Med. 2003;168(11):1358-65.
42. Franks ME, Macpherson GR, Figg WD. Thalidomide. Lancet. 2004;363(9423):1802-11.
43. Vargesson N. Thalidomide‐induced teratogenesis: History and mechanisms. Birth Defects Res C Embryo Today. 2015;105(2):140-56.
44. Tabata C, Tabata R, Kadokawa Y, et al. Thalidomide prevents bleomycin-induced pulmonary fibrosis in mice. J Immunol. 2007;179(1):708-14.
45. Yedinak KC, Lopez LM. Felodipine: a new dihydropyridine calcium-channel antagonist. DICP. 1991;25(11):1193-206.
46. Navadiya K, Tiwari S. Pharmacology, efficacy and safety of felodipine with a focus on hypertension and angina pectoris. Curr Drug Saf. 2015;10(3):194-201.
47. Tanaka K-i, Niino T, Ishihara T, et al. Protective and therapeutic effect of felodipine against bleomycin-induced pulmonary fibrosis in mice. Sci Rep. 2017;7(1):1-12.
48. Gillman P. Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Brit J Pharmacol. 2007;151(6):737-48.
49. Zaafan MA, Haridy AR, Abdelhamid AM. Amitriptyline attenuates bleomycin-induced pulmonary fibrosis: modulation of the expression of NF-κβ, iNOS, and Nrf2. Naunyn Schmiedebergs Arch Pharmacol. 2019;392(3):279-86.
50. Rodriguez BSQ, Correa R. Gemfibrozil. StatPearls [Internet]: StatPearls Publishing; 2022.
51. Mohammadi Y, Khodayar MJ, Hemmati A, Mansouri E. The preventive role of gemfibrozil on bleomycin-induced lung injury and fibrosis in rats. Jundishapur Journal of Natural Pharmaceutical Products. 2017;12(3 (Supp));e64314.
| Files | ||
| Issue | Vol 11, No 1 (Winter 2023) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/jpc.v11i1.12638 | |
| Keywords | ||
| Bleomycin; Lung Injury; Antioxidant; Anti-inflammatory | ||
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How to Cite
1.
Ayoubifar M, Abedi F, Moeini Nodeh M, Arasteh O. Pharmacological Approach for Prevention of Bleomycin-Induced Lung Injury. J Pharm Care. 2023;11(1):32-39.
