Abstract
This study aimed to investigate the protective effects of apigenin against paraquat (PQ)-induced acute lung injury (ALI) in mice. Male Kunming mice were randomly divided into five groups: group 1 (control), group 2 (PQ), group 3 (PQ + apigenin 25 mg/kg), group 4 (PQ + apigenin 50 mg/kg), and group 5 (PQ + apigenin 100 mg/kg). The PQ + apigenin group received apigenin by gavage daily for consecutive 7 days, respectively, while the mice in control and PQ groups were given an equivalent volume of saline. We detected the lung wet/dry weight ratios and the histopathology of the lung. The levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were determined using enzyme-linked immunosorbent assay (ELISA) kits. The activity of nuclear factor (NF)-κB was also determined. The results indicated that apigenin administration decreased biochemical parameters of inflammation and oxidative stress, and improved oxygenation and lung edema in a dose-dependent manner. These protective effects of apigenin were associated with inhibition of NF-κB. In conclusion, apigenin reduces PQ-induced ALI by inhibition of inflammation and oxidative stress.
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Tortorelli, M.C., D.A. Hernández, G. Rey Vázquez, and A. Salibián. 1990. Effects of paraquat on mortality and cardiorespiratory function of catfish fry Plecostomus commersoni. Archives of Environmental Contamination and Toxicology 19(4): 523–529.
Bromilow, R.H. 2004. Paraquat and sustainable agriculture. Pest Management Science 60(4): 340–349.
Chen, J., T. Zeng, Y. Bi, Z. Zhong, K. Xie, and X. Zhao. 2013. Docosahexaenoic acid (DHA) attenuated paraquat induced lung damage in mice. Inhalation Toxicology 25(1): 9–16.
Sabzghabaee, A.M., N. Eizadi-Mood, K. Montazeri, A. Yaraghi, and M. Golabi. 2010. Fatality in paraquat poisoning. Singapore Medical Journal 51(6): 496–500.
Zerin, T., Y.S. Kim, S.Y. Hong, and H.Y. Song. 2012. Protective effect of methylprednisolone on paraquat-induced A549 cell cytotoxicity via induction of efflux transporter, P-glycoprotein expression. Toxicology Letters 208(2): 101–107.
Dinis-Oliveira, R.J., P.G. de Pinho, L. Santos, et al. 2009. Postmortem analyses unveil the poor efficacy of decontamination, anti-inflammatory and immunosuppressive therapies in paraquat human intoxications. PLoS One 4(9): e7149.
Dinis-Oliveira, R.J., J.A. Duarte, A. Sánchez-Navarro, F. Remiao, M.L. Bastos, and F. Carvalho. 2008. Paraquat poisonings: mechanisms of lung toxicity, clinical features, and treatment. Critical Reviews in Toxicology 38(1): 13–71.
Tomita, M., T. Okuyama, H. Katsuyama, et al. 2007. Mouse model of paraquat-poisoned lungs and its gene expression profile. Toxicology 231(2–3): 200–209.
Grommes, J., and O. Soehnlein. 2011. Contribution of neutrophils to acute lung injury. Molecular Medicine 17(3–4): 293–307.
Tao, W., Y.S. Shu, Q.B. Miao, and Y.B. Zhu. 2012. Attenuation of hyperoxia-induced lung injury in rats by adrenomedullin. Inflammation 35(1): 150–157.
Tao, W., Q.B. Miao, Y.B. Zhu, and Y.S. Shu. 2012. Inhaled neutrophil elastase inhibitor reduces oleic acid-induced acute lung injury in rats. Pulmonary Pharmacology & Therapeutics 25(1): 99–103.
Dang, H., S. Wang, L. Yang, F. Fang, and F. Xu. 2012. Upregulation of Shh and Ptc1 in hyperoxia-induced acute lung injury in neonatal rats. Molecular Medicine Reports 6(2): 297–302.
Margolis, A.M., S. Porasuphatana, and G.M. Rosen. 2000. Role of paraquat in the coupling of nitric oxide synthase. Biochimica et Biophysica Acta 1524(2–3): 253–257.
Lin, Y.C., Y.S. Lai, and T.C. Chou. 2013. The protective effect of alpha-lipoic acid in lipopolysaccharide-induced acute lung injury is mediated by heme oxygenase-1. Evidence-Based Complementary and Alternative Medicine 2013: 590363.
Chen, J., Y. Mo, C.F. Schlueter, and G.W. Hoyle. 2013. Inhibition of chlorine-induced pulmonary inflammation and edema by mometasone and budesonide. Toxicology and Applied Pharmacology 272(2): 408–413.
Lefort, É.C., and J. Blay. 2013. Apigenin and its impact on gastrointestinal cancers. Molecular Nutrition & Food Research 57(1): 126–144.
Rice-Evans, C. 2001. Flavonoid antioxidants. Current Medicinal Chemistry 8(7): 797–807.
Patel, D., S. Shukla, and S. Gupta. 2007. Apigenin and cancer chemoprevention: progress, potential and promise (review). International Journal of Oncology 30(1): 233–245.
Shukla, S., and S. Gupta. 2010. Apigenin: a promising molecule for cancer prevention. Pharmaceutical Research 27(6): 962–978.
Fu, M.S., B.J. Zhu, and D.W. Luo. 2014. Apigenin prevents TNF-alpha induced apoptosis of primary rat retinal ganglion cells. Cellular and Molecular Biology (Noisy-le-Grand, France) 60(4): 37–42.
Wang, T., X. Zhang, and J.J. Li. 2002. The role of NF-kappaB in the regulation of cell stress responses. International Immunopharmacology 2(11): 1509–1520.
Kang, J.L., H.W. Lee, H.S. Lee, et al. 2001. Genistein prevents nuclear factor-kappa B activation and acute lung injury induced by lipopolysaccharide. American Journal of Respiratory and Critical Care Medicine 164(12): 2206–2212.
Wright, J.G., and J.W. Christman. 2003. The role of nuclear factor kappa B in the pathogenesis of pulmonary diseases: implications for therapy. American Journal of Respiratory Medicine 2(3): 211–219.
Xia, Y.F., B.Q. Ye, Y.D. Li, et al. 2004. Andrographolide attenuates inflammation by inhibition of NF-kappa B activation through covalent modification of reduced cysteine 62 of p50. Journal of Immunology 173(6): 4207–4217.
Ghosh, S., M.J. May, and E.B. Kopp. 1998. NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annual Review of Immunology 16: 225–260.
Li, Q., and I.M. Verma. 2002. NF-kappa B regulation in the immune system. Nature Reviews Immunology 2(10): 725–734.
Johansson, M.W., M. Patarroyo, F. Oberg, A. Siegbahn, and K. Nilson. 1997. Myeloperoxidase mediates cell adhesion via the alpha M beta 2 integrin (Mac-1, CD11b/CD18). Journal of Cell Science 110(Pt 9): 1133–1139.
Erten, S.F., A. Kocak, I. Ozdemir, S. Aydemir, A. Colak, and B.S. Reeder. 2003. Protective effect of melatonin on experimental spinal cord ischemia. Spinal Cord 41(10): 533–538.
Shaafi, S., M. Afrooz Razm, B. Hajipour, A. Dadadshi, M.M. Hosseinian, and A. Khodadadi. 2011. Anti-oxidative effect of lipoic acid in spinal cord ischemia/reperfusion. Medical Principles and Practice 20(1): 19–22.
Qian, H., and D. Liu. 1997. The time course of malondialdehyde production following impact injury to rat spinal cord as measured by microdialysis and high pressure liquid chromatography. Neurochemical Research 22(10): 1231–1236.
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All animal experiments were performed in accordance with the Institutional Animal Care Committee of Yuhuangding Hospital.
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Luan, RL., Meng, XX. & Jiang, W. Protective Effects of Apigenin Against Paraquat-Induced Acute Lung Injury in Mice. Inflammation 39, 752–758 (2016). https://doi.org/10.1007/s10753-015-0302-2
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DOI: https://doi.org/10.1007/s10753-015-0302-2