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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This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
All animal experiments were performed in accordance with the Institutional Animal Care Committee of Yuhuangding Hospital.
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.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedGoogle Scholar
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.PubMedGoogle Scholar
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.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedPubMedCentralGoogle Scholar
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.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedGoogle Scholar
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.CrossRefGoogle Scholar
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.PubMedGoogle Scholar
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.CrossRefPubMedGoogle Scholar
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.PubMedPubMedCentralGoogle Scholar
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.CrossRefPubMedPubMedCentralGoogle Scholar
Lefort, É.C., and J. Blay. 2013. Apigenin and its impact on gastrointestinal cancers. Molecular Nutrition & Food Research 57(1): 126–144.CrossRefGoogle Scholar
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.Google Scholar
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.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedGoogle Scholar
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.CrossRefGoogle Scholar
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.CrossRefPubMedGoogle Scholar
Li, Q., and I.M. Verma. 2002. NF-kappa B regulation in the immune system. Nature Reviews Immunology 2(10): 725–734.CrossRefPubMedGoogle Scholar
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.PubMedGoogle Scholar
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.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedGoogle Scholar