Keywords
diisononyl phthalates
asthma
lungs
ellagic acid
mice
How to Cite
Abstract
Polyvinyl chloride is plasticized using diisononyl phthalate (DiNP), and exposure to phthalates has been linked to the emergence of asthma and allergies. The adjuvant impact of DiNP exposure results in allergic airway inflammation. In the current study, we looked into how ellagic acid (ELA) impacted asthma brought on by DiNP. Male BALB/c mice (n=40, 20-30 g) were divided into 4 groups of 10 mice each, and the following treatments were given to each group: group 1 (control) received saline orally for 30 days; group 2 (ELA) received 10 mg/kg of ELA (oral) for 30 days; group 3 (DiNP & ELA) received 10 mg/kg of ELA (oral) for 7 days prior to DiNP (50mg/kg) exposure (intraperitoneal and intranasal); group 4 (DiNP) received 50 mg/kg DiNP. After the last administration, mice were sacrificed, lungs were removed and their bronchoalveolar lavage fluid was collected which was used for biochemical and histopathological analysis. The mice given DiNP had changes in their histoarchitecture, inflammatory cells, antioxidant status, and inflammation markers. Malondialdehyde (MDA) and inflammatory biomarkers (NO, MPO) were considerably higher (p< 0.05) in the lungs of DiNP-treated mice than in the control group. In the lungs, DiNP reduced the concentration of non-enzymatic antioxidants (GSH and AA), and the activity of enzymatic antioxidants (SOD, CAT, and GST). DiNP also altered inflammatory cells (eosinophils, neutrophils, lymphocytes, monocytes, leucocytes) in the BALF. ELA administration ameliorated these changes. Histopathological analysis revealed airway inflammation characterized by inflammatory cell infiltration, oedema, hemorrhage, and constricted alveoli space. Additionally, the mice co-treated with ELA and DiNP experienced mild inflammation of the alveoli and interstitial spaces as well as mild thickening of the alveolar septae. ELA offered a protective effect against DiNP-induced allergic asthma in mice.
References
Ajayi, B. O., Olajide, T. A., & Olayinka, E. T. (2022). 6-gingerol attenuates pulmonary inflammation and oxidative stress in mice model of house dust mite-induced asthma. Advances in Redox Research, 5, 100036.
https://doi.org/10.1016/j.arres.2022.100036
Barnes, P. J. (2020). Oxidative stress-based therapeutics in COPD. Redox Biology, 33, 101544.
https://doi.org/10.1016/j.redox.2020.101544
Bornehag, C., & Nånberg, E. (2010). Phthalate exposure and asthma in children. International Journal of Andrology, 33(2), 333–345.
https://doi.org/10.1111/j.1365-2605.2009.01023.x
Chen, L., Chen, J., Xie, C.M., Zhao, Y., Wang, X., & Zhang, Y.H. (2015). Maternal disononyl phthalate exposure activates allergic airway inflammation via stimulating the phosphoinositide 3-kinase/Akt pathway in rat pups. Biomedical and Environmental Sciences, 28, 190-198.
https://doi.org/10.3967/bes2015.025
Chen, L., Zhao, Y., Li, L., Chen, B., & Zhang, Y. (2012). Exposure assessment of phthalates in non-occupational populations in China. Science of the Total Environment, 427-428, 60-69.
Chen, L. Q., Zhao, Y., Li, L., Chen, B., & Zhang, Y. (2012). Exposure assessment of phthalates in non-occupational populations in China. Science of the Total Environment, 427–428, 60–69.
https://doi.org/10.1016/j.scitotenv.2012.03.090
Chiu, K., Bashir, S. T., Nowak, R. A., Mei, W., & Flaws, J. A. (2020). Subacute exposure to di-isononyl phthalate alters the morphology, endocrine function, and immune system in the colon of adult female mice. Scientific Reports, 10(1).
https://doi.org/10.1038/s41598-020-75882-0
Choi, Y. S., & Yan, G. (2009). Ellagic acid attenuates immunoglobulin E-mediated allergic response in mast cells. Biological & Pharmaceutical Bulletin, 32(6), 1118–1121.
https://doi.org/10.1248/bpb.32.1118
Claiborne, A. (1985). Catalase activity. In: Greenwald, R.A., Ed., Handbook Methods for Oxygen Radical Research, CRC Press, Boca Raton, 283-284.
Favarin, D. C., Teixeira, M. M., De Andrade, E. L., De Freitas Alves, C., Chica, J. C., Sorgi, C. A., Faccioli, L. H., & De Paula Rogerio, A. (2013). Anti-inflammatory effects of ellagic acid on acute lung injury induced by acid in mice. Mediators of Inflammation, 1–13.
https://doi.org/10.1155/2013/164202
Dodson, R. E., Nishioka, M., Standley, L. J., Perovich, L. J., Brody, J. G., & Rudel, R. A. (2012). Endocrine disruptors and asthma-associated chemicals in consumer products. Environmental health perspectives, 120(7), 935-943.
Dodson, R. E., Nishioka, M., Standley, L. J., Perovich, L. J., Brody, J. G., & Rudel, R. A. (2012). Endocrine disruptors and asthma-associated chemicals in consumer products. Environmental Health Perspectives, 120(7), 935–943.
https://doi.org/10.1289/ehp.1104052
Elieh Ali Komi, D., & Bjermer, L. (2019). Mast cell-mediated orchestration of the immune responses in human allergic asthma: current insights. Clinical reviews in allergy & immunology, 56, 234-247.
https://doi.org/10.1007/s12016-018-8720-1
Fahy, J. V. (2009). Eosinophilic and neutrophilic inflammation in asthma: insights from clinical studies. Proceedings of the American Thoracic Society, 6(3), 256-259.
https://doi.org/10.1513/pats.200808-087RM
Fischer, A. H., Jacobson, K. A., Rose, J., & Zeller, R. (2008). Hematoxylin and Eosin Staining of Tissue and Cell Sections. CSH Protocols, pdb.prot4986.
https://doi.org/10.1101/pdb.prot4986
García-Niño, W. R., & Zazueta, C. (2015). Ellagic acid: Pharmacological activities and molecular mechanisms involved in liver protection. Pharmacological Research, 97, 84-103.
https://doi.org/10.1016/j.phrs.2015.04.008
Green, L. C., Wagner, D. A., Glogowski, J., Skipper, P. L., Wishnok, J. S., & Tannenbaum, S. R. (1982). Analysis of nitrate, nitrite and (15N) nitrate in biological fluids. Analytical Biochemistry, 126,131-138.
https://doi.org/10.1016/0003-2697(82)90118-X
Habig, W. H., Pabst, M. J., & Jakoby, W. B. (1974). Glutathione S-transferases: the first enzymatic step in mercapturic acid formation. Journal of Biological Chemistry, 249(22), 7130-7139.
https://doi.org/10.1016/S0021-9258(19)42083-8
Hosseini, B., Berthon, B.S., Wark, P., & Wood, L.G. (2017). Effects of fruit and vegetable consumption on risk of asthma, wheezing and immune responses: a systematic review and meta-analysis. Nutrients, 9, 341.
https://doi.org/10.3390/nu9040341
Hwang, Y. H., Paik, M. J., & Yee, S. T. (2017). Diisononyl phthalate induces asthma via modulation of Th1/Th2 equilibrium. Toxicology letters, 272, 49-59.
https://doi.org/10.1016/j.toxlet.2017.03.014
Ilmarinen, P., Tuomisto, L. E., & Kankaanranta, H. (2015). Phenotypes, risk factors, and mechanisms of adult-onset asthma. Mediators of Inflammation, 2015.
https://doi.org/10.1155/2015/514868
Jaakkola, J.J., & Knight, T.L. (2008). The role of exposure to phthalates from polyvinyl chloride products in the development of asthma and allergies: a systematic review and meta-analysis. Environmental Health Perspectives, 116, 845-853.
https://doi.org/10.1289/ehp.10846
Jagota, S. K., & Dani, H. M. (1982). A new colorimetric technique for the estimation of vitamin C using Folin phenol reagent. Analytical Biochemistry, 127(1): 178-182.
https://doi.org/10.1016/0003-2697(82)90162-2
Jesenak, M., Zelieskova, M., & Babusikova, E. (2017). Oxidative stress and bronchial asthma in children-causes or consequences? Frontiers in Pediatrics, 5, 162.
https://doi.org/10.3389/fped.2017.00162
Jollow, D. J., Mitchell, J. R., Zampaglione, N., & Gillette, J. R. (1974). Bromobenzene induced liver necrosis, Protective role of glutathione and evidence for 3, 4 bromobenzene oxide as the toxic metabolite. Pharmacology II, 151-169.
https://doi.org/10.1159/000136485
Kato, T., Tada-Oikawa, S., Takahashi, K., Saito, K., Wang, L., Nishio, A., Hakamada- Taguchi, R., Kawanishi, S., & Kuribayashi, K. (2006). Endocrine disruptors that deplete glutathione levels in APC promote Th2 polarization in mice leading to the exacerbation of airway inflammation. Eur. J. Immunol, 36, 1199-1209.
https://doi.org/10.1002/eji.200535140
Khazaei, A., Mansouri, S. M. T., Siahpoosh, A., Ghorbanzadeh, B., Salehi, S., & Khodayar, M. J. (2019). Ameliorative effects of ellagic acid on maximal electroshock and pentylenetetrazole-induced seizures in mice. Jundishapur Journal of Natural Pharmaceutical Products, 14(3).
https://doi.org/10.5812/jjnpp.80039
Kim, J. J., Shajib, M. S., Manocha, M. M., & Khan, W. I. (2012). Investigating Intestinal Inflammation in DSS-induced Model of IBD. Journal of Visualized Experiments, 60.
https://doi.org/10.3791/3678-v
Larsen, S.T., Lund, R.M., Nielsen, G.D., & Thygesen, P. (2002). Poulsen OM. Adjuvant effect of di-n-butyl- di-n-octyl-, di-iso-nonyl- and di-iso-decyl phthalate in a subcutaneous injection model using BALB/c mice. Pharmacology & Toxicology, 91, 264- 272.
https://doi.org/10.1034/j.1600-0773.2002.910508.x
Lewis, B.W., Ford, M.L., Rogers, L.K. & Britt, R.D. (2021). Oxidative stress promotes corticosteroid insensitivity in asthma and COPD. Antioxidants, 10, 1335.
https://doi.org/10.3390/antiox10091335
Lin, T. Y., Venkatesan, N., Mahboub, B., & Hamid, Q. (2013). Involvement of lymphocytes in asthma and allergic diseases: a genetic point of view. Current Opinion in Allergy and Clinical Immunology, 13(5), 500-506.
https://doi.org/10.1097/ACI.0b013e328364ea3a
Maruthamuthu, V., Henry, L. J. K., Ramar, M. K., & Kandasamy, R. (2020). Myxopyrum serratulum ameliorates airway inflammation in LPS-stimulated RAW 264.7 macrophages and OVA-induced murine model of allergic asthma. Journal of Ethnopharmacology, 255, 112369.
https://doi.org/10.1016/j.jep.2019.112369
Mishra, V., Banga, J., & Silveyra, P. (2018). Oxidative stress and cellular pathways of asthma and inflammation: Therapeutic strategies and pharmacological targets. Pharmacology & Therapeutics, 181,169-182.
https://doi.org/10.1016/j.pharmthera.2017.08.011
Ndrepepa, G. (2019). Myeloperoxidase-A bridge linking inflammation and oxidative stress with cardiovascular disease. Clinica Chimica Acta, 493, 36-51.
https://doi.org/10.1016/j.cca.2019.02.022
Oishi, H., Takano, K., Tomita, K., Takebe, M., Yokoo, H., Yamazaki, M., & Hattori, Y. (2012). Olprinone and colforsin daropate alleviate septic lung inflammation and apoptosis through CREB‐independent activation of the Akt pathway. American Journal of Physiology Lung Cellular and Molecular Physiology, 303(2), L130-L140.
https://doi.org/10.1152/ajplung.00363.2011
Patel, B.D., Welch, A.A., Bingham, S.A., Luben, R.N., Day, N.E., Khaw, K.T., Lomas, D.A., & Wareham, N. (2006). Dietary antioxidants and asthma in adults. Thorax, 61, 388-393.
https://doi.org/10.1136/thx.2004.024935
Pawankar, R. (2014). Allergic diseases and asthma: a global public health concern and a call to action. World Allergy Organization Journal. 7, 12.
https://doi.org/10.1186/1939-4551-7-12
Promsong, A., Wo, C., Satthakarn, S., & Nittayananta, W. (2014). Ellagic acid modulatesthe expression of oral innate immune mediators: potential role in mucosalprotection, Journal of Oral Pathology & Medicine.
https://doi.org/10.1111/jop.12223
Qu, X., Tang, Y., & Hua, S. (2018). Immunological approaches towards cancer and inflammation: a cross talk. Frontiers in Immunology, 9, 563.
https://doi.org/10.3389/fimmu.2018.00563
Radermecker, C., Louis, R., Bureau, F., & Marichal, T. (2018). Role of neutrophils in allergic asthma. Current Opinion in Immunology, 54, 28-34.
https://doi.org/10.1016/j.coi.2018.05.006
Ramirez-Velazquez, C., Castillo, E. C., Guido-Bayardo, L., & Ortiz-Navarrete, V. (2013). IL-17-producing peripheral blood CD177+ neutrophils increase in allergic asthmatic subjects. Allergy, Asthma & Clinical Immunology, 9, 1-8.
https://doi.org/10.1186/1710-1492-9-23
Rayees, S., & Din, I. (2021). Inflammatory Cells Involved in Asthma. In: Asthma: Pathophysiology, Herbal and Modern Therapeutic Interventions. SpringerBriefs in Immunology. Springer, Cham.
https://doi.org/10.1007/978-3-030-70270-0
Saba, Khan, S., Parvez, S., Chaudhari, B. P., Ahmad, F., Anjum, S., & Raisuddin, S. (2013). Ellagic acid attenuates bleomycin and cyclophosphamide-induced pulmonary toxicity in Wistar rats. Food and Chemical Toxicology, 58, 210–219.
https://doi.org/10.1016/j.fct.2013.03.046
Sahiner, U. M., Birben, E., Erzurum, S., Sackesen, C., & Kalayci, Ö. (2018). Oxidative stress in asthma: Part of the puzzle. Pediatric Allergy and Immunology, 29(8), 789-800.
https://doi.org/10.1111/pai.12965
Shastri, M. D., Chong, W. C., Dua, K., Peterson, G. M., Patel, R. P., Mahmood, M. Q., Tambuwala, M., Chellappan, D. K., Hansbro, N. G., Shukla, S. D., & Hansbro, P. M. (2021). Emerging concepts and directed therapeutics for the management of asthma: regulating the regulators. Inflammopharmacology, 29(1):15-33.
https://doi.org/10.1007/s10787-020-00770-y
Silveira, J. S., Antunes, G. L., Kaiber, D. B., da Costa, M. S., Marques, E. P., Ferreira, F. S., ... & da Cunha, A. A. (2019). Reactive oxygen species are involved in eosinophil extracellular traps release and in airway inflammation in asthma. Journal of Cellular Physiology, 234(12), 23633-23646.
https://doi.org/10.1002/jcp.28931
Soong, Y. Y., & Barlow, P. J. (2006). Quantification of gallic acid and ellagic acid from longan (Dimocarpus longan Lour.) seed and mango (Mangifera indica L.) kernel and their effects on antioxidant activity. Food Chemistry, 97(3), 524-530.
https://doi.org/10.1016/j.foodchem.2005.05.033
Southam, D. S., Ellis, R., Wattie, J., & Inman, M. D. (2007). Components of airway hyperresponsiveness and their associations with inflammation and remodeling in mice. Journal of Allergy and Clinical Immunology, 119(4), 848-854.
https://doi.org/10.1016/j.jaci.2006.12.623
Sun, M., & Zigman, S. (1978). An improved spectrophotometric assay for superoxide dismutase based on epinephrine autoxidation. Analytical Biochemistry, 90(1), 81-89.
https://doi.org/10.1016/0003-2697(78)90010-6
Tang, W., Dong, M., Teng, F., Cui, J., Zhu, X., Wang, W., ... & Wei, Y. (2021). Environmental allergens house dust mite induced asthma is associated with ferroptosis in the lungs. Experimental and Therapeutic Medicine, 22(6), 1-10.
https://doi.org/10.3892/etm.2021.10918
Varshney, R., & Kale, R. K. (1990). Effects of Calmodulin Antagonists on Radiation-induced Lipid Peroxidation in Microsomes. International Journal of Radiation Biology, 58(5): 733-743.
https://doi.org/10.1080/09553009014552121
Vincent, M. J., Bernstein, J. A., Basketter, D., LaKind, J. S., Dotson, G. S., & Maier, A. (2017). Chemical-induced asthma and the role of clinical, toxicological, exposure and epidemiological research in regulatory and hazard characterization approaches. Regulatory Toxicology and Pharmacology, 90, 126-132.
https://doi.org/10.1016/j.yrtph.2017.08.018
Wang, Y., Xu, J., Meng, Y., Adcock, I. M., & Yao, X. (2018). Role of inflammatory cells in airway remodeling in COPD. International journal of chronic obstructive pulmonary disease, 3341-3348.
https://doi.org/10.2147/COPD.S176122
Wu, T. D., Brigham, E. P., & McCormack, M. C. (2019). Asthma in the primary care setting. Medical Clinics, 103(3), 435-452.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright (c) 2023 Abosede Temitope Olajide, Ebenezer Tunde Olayinka , Ayokanmi Ore, Samuel Abiodun Kehinde, Cynthia Chisom Okoye