Protective effects of N-acetylcysteine against irinotecan – induced pulmonary toxicity in female albino rats
DOI:
https://doi.org/10.15218/zjms.2024.35Keywords:
Lung, Idiopathic pulmonary fibrosis (IPF), Irinotecan (IRI), N-acetylcysteine, CollagenAbstract
Background and objective: Idiopathic pulmonary fibrosis (IPF) is a deadly lung illness characterized by progressive lung fibrosis and deteriorating lung function, with the uncertain origin and few therapeutic options. Chemotherapy such as Irinotecan (IRI) is the major antineoplastic agent that produces IPF and induces lung damage. N-acetylcysteine (NAC) has a glutathionepre cursor that protects lung function. The present study was designed to evaluate the protective effects of N-acetylcysteine in Irinotecan induced lung toxicity.
Methods: In total, 18 female Albino rats were divided into three groups, aging from 8-12 weeks and weighing between 180-250 g. The control group G1 received 1 ml intraperitoneal (IP) normal saline for 14 days, G2 Irinotecan group was administered a single high dose of Irinotecan (300 mg/kg) intraperitoneal instillation. And G3 N-acetylcysteine group (500 mg/kg/day) orally one week before Irinotecan (300 mg/kg) injection continued to the end of 21 days of the experimental period. Histopathology, cell counts, cytokine responses in the serum (TGF-β, TNF-α, and IL-6), and weight measurements were studied to evaluate the protective effects.
Results: Histopathological study indicated the Irinotecan–induced pulmonary fibrosis with a significant increase in the levels of inflammatory cytokines, and the protective impacts of N-acetylcysteine administration attenuated the degree of inflammation and fibrosis with a reduced level of cytokines concentrations in serum.
Conclusion: N-acetylcysteine can protect the lungs from both histological alterations and activation of cytokines caused by pulmonary toxicity induced by Irinotecan.
Metrics
References
Maher TM, Bendstrup E, Dron L, Langley J, Smith G, Khalid JM, et al. Global incidence and prevalence of idiopathic pulmonary fibrosis. Respir Res 2021; 22(1):197. https://doi.org/10.1186/s12931-021-01791-z
Ermis H, Parlakpinar H, Gulbas G, Vardi N, Polat A, Cetin A, et al. Protective effect of dexpanthenol on bleomycin-induced pulmonary fibrosis in rats. Naunyn Schmiedebergs Arch Pharmacol 2013; 386(12):1103–10. https://doi.org/10.1007/s00210-013-0908-6.
Li LC, Xu L, Hu Y, Cui WJ, Cui WH, Zhou WC, et al. Astragaloside IV Improves Bleomycin-Induced Pulmonary Fibrosis in Rats by Attenuating Extracellular Matrix Deposition. Front Pharmacol 2017; 8:513. https://doi.org/10.3389/fphar.2017.00513.
Marcon A, Schievano E, Fedeli U. Mortality Associated with Idiopathic Pulmonary Fibrosis in Northeastern Italy, 2008–2020: A Multiple Cause of Death Analysis. Int J Environ Res Public Health 2021; 18(14):7249. https://doi.org/10.3390/ijerph18147249.
Kalemci S, Tanrıverdi O, Şimşek A, Aksun S, Celik OI, Barutca S, et al. Evaluation of oxaliplatin-induced pulmonary toxicity in rats. Contemp Oncol (Pozn) 2019; 23(3):151–6. https://doi.org/10.5114/wo.2019.89242.
Li L, Mok H, Jhaveri P, Bonnen MD, Sikora AG, Eissa NT, et al. Anticancer therapy and lung injury: molecular mechanisms. Expert Rev Anticancer Ther 2018; 18(10):1041–57. https://doi.org/10.1080/14737140.2018.1500180.
Bailly C. Irinotecan: 25 years of cancer treatment. Pharmacol Res 2019;148:104398. https://doi.org/10.1080/14737140.2018.1500180.
Ozawa Y, Koda K, Akahori D, Matsui T, Hasegawa H, Kakutani T, et al. Preexisting Interstitial Lung Disease and Lung Injury Associated with Irinotecan in Patients with Neoplasms. Anticancer Research 2018; 38(10):5937–41. https://doi.org/10.21873/anticanres.12939.
Meng L, Deng B, Liu B, Majeed U, Wang W. A Rare Case of Irinotecan-induced Interstitial Pulmonary Disease and Diffuse Alveolar Hemorrhage in a Patient with Pancreatic Cancer. Cureus 2019; 11(6):e5041. https://doi.org/10.7759/cureus.5041.
Schwalfenberg GK. N-Acetylcysteine: A Review of Clinical Usefulness (an Old Drug with New Tricks). J Nutr Metab 2021; 2021:9949453. https://doi.org/10.1155/2021/9949453.
Kahraman H, Kurutaş E, Tokur M, Bozkurt S, Çıralık H, Kabakcı B, et al. Protective Effects of Erythropoietin and N-Acetylcysteine on Methotrexate-Induced Lung Injury in Rats. Balkan Med J 2013; 30(1):99–104. https://doi.org/10.5152/balkanmedj.2012.078.
Al-hamdany M, Al-Hubaity A. Protective Effects of N-acetylcysteine against 5-Fluorouracil- Induced Pulmonary Toxicity in Albino Rats. Iraq J Med 2014; 12(2):139–49.
Yao Y, Zhang P, Wang J, Chen J, Wang Y, Huang Y, et al. Dissecting Target Toxic Tissue and Tissue Specific Responses of Irinotecan in Rats Using Metabolomics Approach. Frontiers in Pharmacology 2017; 8:122. https://doi.org/10.3389/fphar.2017.00122.
Zhang H, Yin G, Jiang H, Zhang C. High-dose N-acetylcysteine decreases silica-induced lung fibrosis in the rat. J Int Med Res 2013; 41(4):1179–86. https://doi.org/10.1177/0300060513488503.
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. https://doi.org/10.3390/ijms141224476.
Michielin O, Udry E, Périard D, Matzinger O, Lobrinus JA, Stupp R. Irinotecan-induced interstitial pneumonia. Lancet Oncol 2004; 5(5):322–4. https://doi.org/10.1016/S1470-2045(04)01471-8.
Aoyagi H, Ito H, Higuchi K, Koseki K, Watanabe I, Tanaka Y, et al. [A Case of Fatal Interstitial Pneumonia during FOLFIRI plus Cetuximab Therapy for Liver Metastasis of Colon Cancer]. Gan To Kagaku Ryoho 2018; 45(1):51–3. PMID: 29362307
Kim YS, Li Q, Youn HY, Kim DY. Oral Administration of Chitosan Attenuates Bleomycin-induced Pulmonary Fibrosis in Rats. In Vivo 2019; 33(5):1455–61. https://doi.org/10.21873/invivo.11624.
Hatipoglu OF, Uctepe E, Opoku G, Wake H, Ikemura K, Ohtsuki T, et al. Osteopontin silencing attenuates bleomycin-induced murine pulmonary fibrosis by regulating epithelial-mesenchymal transition. Biomed Pharmacother 2021; 139:111633. https://doi.org/10.1016/j.biopha.2021.111633.
Tang L, Li X, Wan L, Xiao Y, Zeng X, Ding H. Herbal Medicines for Irinotecan-Induced Diarrhea. Front Pharmacol 2019 ;10:182. https://doi.org/10.3389/fphar.2019.00182
Chitra P, Saiprasad G, Manikandan R, Sudhandiran G. Berberine attenuates bleomycin induced pulmonary toxicity and fibrosis via suppressing NF-κB dependant TGF-β activation: a biphasic experimental study. Toxicol Lett 2013; 219(2):178–93. https://doi.org/10.1016/j.toxlet.2013.03.009.
Fathimath Muneesa M, Shaikh SB, Jeena TM, Bhandary YP. Inflammatory mediators in various molecular pathways involved in the development of pulmonary fibrosis. Int Immunopharmacol 2021; 96:107608. https://doi.org/10.1016/j.intimp.2021.107608
She YX, Yu QY, Tang XX. Role of interleukins in the pathogenesis of pulmonary fibrosis. Cell Death Discov 2021; 7(1):52. https://doi.org/10.1038/s41420-021-00437-9
Zhang Q, Ju Y, Ma Y, Wang T. N-acetylcysteine improves oxidative stress and inflammatory response in patients with community acquired pneumonia. Medicine (Baltimore) 2018; 97(45):e13087. https://doi.org/10.1097/MD.0000000000013087
Kanaji N, Shimizu J, Sakai K, Ueda Y, Miyawaki H, Watanabe N, et al. Clinical features of patients with small cell lung cancer and idiopathic pulmonary fibrosis treated with chemotherapy or chemoradiotherapy. Ther Adv Respir Dis 2020; 14:1753466620963866.
Farag A, Faruk E, Kharboush T, Abu-Raia NH, Fakher HM. Protective effect of N-acetylcysteine (NAC) against Di-ethylhexyl phthalate (DEHP) induced pulmonary toxicity in male albino rats (histological and immunohistochemical study). The EJFSAT 2021; 21(2):89–109. https://doi.org/10.21608/ejfsat.2020.27601.1138
Chen H, Ma N, Song X, Wei G, Zhang H, Liu J, et al. Protective Effects of N-Acetylcysteine on Lipopolysaccharide-Induced Respiratory Inflammation and Oxidative Stress. Antioxidants 2022; 11(5):879. https://doi.org/10.3390/antiox11050879
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Hawrin Burhan Khudhur, Ansam Al-Hassani (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The copyright on any article published in Zanco J Med Sci is retained by the author(s) in agreement with the Creative Commons Attribution Non-Commercial ShareAlike License (CC BY-NC-SA 4.0).
