Abstract
Paraquat (PQ) induces pulmonary fibrosis, a progressive lung disorder resulting in severe respiratory failure and death. Increased oxidative stress, inflammatory reactions, and multiple fibrotic lesions are major features of PQ-induced lung injury. Diosmin (Dio) is a safe drug that is available for clinical use for vascular disorders. Dio exhibits antioxidant, anti-inflammatory, and antifibrotic activities. Accordingly, the aim of this study was to evaluate the protective effect of diosmin on PQ-induced lung injury in mice and the underlying mechanisms involved. Lung injury was induced by PQ (30 mg/kg, intraperitoneally) in NMRI albino mice and Dio (50 and 100 mg/kg, gavage) was administrated 3 days before PQ and continued for 10 or 24 days. After euthanizing the mice, the biochemical and histopathological markers of lung tissue were determined. PQ significantly increased oxidative stress, inflammatory, and fibrotic markers. PQ increased the level of malonedaldehyde (MDA) and hydroxyproline (HYP) and decreased the level of glutathione (GSH) and catalase activity in the lung. Dio (50 and 100 mg/kg) significantly increased GSH levels and catalase activity and decreased HYP content and MDA levels. In addition, Dio reduced histopathological injuries in hematoxylin and eosin–stained and Masson’s trichrome–stained sections. These findings suggest that Dio has protective effects against PQ-induced lung injury, which may be due to its antioxidant, anti-inflammatory, and antifibrotic effects.
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Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126
Arab HH, Salama SA, Omar HA, Arafa el SA, Maghrabi IA (2015) Diosmin protects against ethanol-induced gastric injury in rats: novel anti-ulcer actions. PLoS One 10(3):e0122417
Ashcroft T, Simpson JM, Timbrell V (1988) Simple method of estimating severity of pulmonary fibrosis on a numerical scale. J Clin Pathol 41:467–470
Autor A (1977) Biochemical mechanisms of paraquat toxicity. Academic Press Inc, New York
Baltazar T, Dinis-Oliveira RJ, Duarte JA, de Lourdes Bastos M, Carvalho F (2013) Paraquat research: do recent advances in limiting its toxicity make its use safer? Br J Pharmacol 168(1):44–45
Bedada SK, Neerati P (2018) Modulation of CYP3A enzyme activity by diosmin and its consequence on carbamazepine pharmacokinetics in rats. Naunyn Schmiedebergs Arch Pharmacol 391(2):115–121
Buddhan R, Manoharan S (2017) Diosmin reduces cell viability of A431 skin cancer cells through apoptotic induction. J Cancer Res Ther 13(3):471–476
Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310
Chaudhary NI, Schnapp A, Park JE (2006) Pharmacologic differentiation of inflammation and fibrosis in the rat bleomycin model. Am J Respir Crit Care Med 173:769–776
Chen Y, Nie Y-c, Luo Y-l, Lin F, Zheng Y-f, Cheng G-h, Wu H, Zhang K-J, Su W-W, Shen J-g (2013) Protective effects of naringin against paraquat-induced acute lung injury and pulmonary fibrosis in mice. Food Chem Toxicol 58:133–140
Cheng Y-H, Chou W-C, Yang Y-F, Huang C-W, How CM, Chen S-C, Chen W-Y, Hsieh N-H, Lin Y-J, You S-H, Liao C-M (2018) PBPK/PD assessment for Parkinson’s disease risk posed by airborne pesticide paraquat exposure. Environ Sci Pollut Res 25:5359–5368
Cortijo J, Cerda-Nicolas M, Serrano A, Bioque G, Estrela JM, Santangelo F, Esteras A, Llombart-Bosch A, Morcillo EJ (2001) Attenuation by oral N-acetylcysteine of bleomycin-induced lung injury in rats. Eur Respir J 17:1228–1235
Crespo ME, Galvez J, Cruz T, Ocete MA, Zarzuelo A (1999) Anti-inflammatory activity of diosmin and hesperidin in rat colitis induced by TNBS. Planta Med 65(7):651–653
Dinis-Oliveira R, Duarte J, Sanchez-Navarro A, Remiao F, Bastos M, Carvalho F (2008) Paraquat poisonings: mechanisms of lung toxicity, clinical features, and treatment. Crit Rev Toxicol 38:13–71
Dong J, Yu X, Porter DW, Battelli LA, Kashon ML, Ma Q (2016) Common and distinct mechanisms of induced pulmonary fibrosis by particulate and soluble chemical fibrogenic agents. Arch Toxicol 90(2):385–402
Edwards C, O’Brien W Jr (1980) Modified assay for determination of hydroxyproline in a tissue hydrolyzate. Clin Chim Acta 104:161–167
Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77
Gawarammana IB, Buckley NA (2011) Medical management of paraquat ingestion. Br J Clin Pharmacol 72:745–757
Heusser J, Osswald W (1977) Toxicological properties of diosmin and its actions on the isolated venous tissue of the dog. Arch Farmacol Toxicol 3:33–40
Imam F, Al-Harbi NO, Al-Harbi MM, Ansari MA, Zoheir KM, Iqbal M, Anwer MK, Al Hoshani AR, Attia SM, Ahmad SF (2015) Diosmin downregulates the expression of T cell receptors, pro-inflammatory cytokines and NF-kappaB activation against LPS-induced acute lung injury in mice. Pharmacol Res 102:1–11
Kumar VCR, Rabbins SL (1997) Basic pathology. W.B. Saunders Company, Philadelphia, p 52
Liu WY, Liou SS, Hong TY, Liu IM (2017) The benefits of the citrus flavonoid diosmin on human retinal pigment epithelial cells under high-glucose conditions. Molecules 22(12):2251
Mahmoud G-K, Ali M-K, Masoud S, Parvin M, Ebraheim P-E, Shirin M (2007) Antifibrotic effect of captopril and enalapril on paraquat-induced lung fibrosis in rats. J Appl Toxicol 27:342–349
Nakagawa I, Suzuki M, Imura N, Naganuma A (1995) Enhancement of paraquat toxicity by glutathione depletion in mice in vivo and in vitro. J Toxicol Sci 20:557–564
Novaes RD, Gonçalves RV, Cupertino MC, Marques D, Rosa DD, Peluzio MCG, Neves CA, Leite JPV (2012) Bark extract of Bathysa cuspidata attenuates extra-pulmonary acute lung injury induced by paraquat and reduces mortality in rats. Int J Exp Pathol 93:225–233
Patel S, Sangeeta S (2018) Pesticides as the drivers of neuropsychotic diseases, cancers, and teratogenicity among agro-workers as well as general public. Environ Sci Pollut Res 26(1):91–100
Pehlivan M, Hazinedaroglu SM, Kayaoglu HA, Erkek AB, Keklik T, Canbolat O, Kocak S (2004) The effect of diosmin hesperidin on intestinal ischaemia--reperfusion injury. Acta Chir Belg 104:715–718
Perumal S, Langeshwaran K, Selvaraj J, Ponnulakshmi R, Shyamaladevi B, Balasubramanian MP (2018) Effect of diosmin on apoptotic signaling molecules in N-nitrosodiethylamine-induced hepatocellular carcinoma in experimental rats. Mol Cell Biochem 449(1-2):27–37
Puglisi S, Torrisi SE, Vindigni V, Giuliano R, Palmucci S, Mulè M, Vancheri C (2016) New perspectives on management of idiopathic pulmonary fibrosis. Ther Adv Chronic Dis 7:108–120
Rehman MU, Tahir M, Quaiyoom Khan A, Khan R, Lateef A, Hamiza OO, Ali F, Sultana S (2013) Diosmin protects against trichloroethylene-induced renal injury in Wistar rats: plausible role of p53, Bax and caspases. Br J Nutr 110:699–710
Rose MS, Smith LL, Wyatt I (1974) Evidence for energy-dependent accumulation of paraquat into rat lung. Nature 252:314–315
Ruscitti F, Ravanetti F, Essers J, Ridwan Y, Belenkov S, Vos W, Ferreira F, KleinJan A, van Heijningen P, Van Holsbeke C, Cacchioli A, Villetti G, Stellari FF (2017) Longitudinal assessment of bleomycin-induced lung fibrosis by Micro-CT correlates with histological evaluation in mice. Multidiscip Respir Med 12:8
Sabzghabaee A, Eizadi-Mood N, Montazeri K, Yaraghi A, Golabi M (2010) Fatality in paraquat poisoning. Singapore Med J 51:496–500
Shalkami AS, Hassan MIA, Bakr AG (2017) Anti-inflammatory, antioxidant and anti-apoptotic activity of diosmin in acetic acid-induced ulcerative colitis. Hum Exp Toxicol 37:78–86
Shariati S, Kalantar H, Pashmforosh M, Mansouri E, Khodayar MJ (2019) Epicatechin protective effects on bleomycin-induced pulmonary oxidative stress and fibrosis in mice. Biomed Pharmacother 114:108776
Shen H, Wu N, Wang Y, Zhao H, Zhang L, Li T, Zhao M (2017) Chloroquine attenuates paraquat-induced lung injury in mice by altering inflammation, oxidative stress and fibrosis. Int Immunopharmacol 46:16–22
Srinivasan S, Pari L (2012) Ameliorative effect of diosmin, a citrus flavonoid against streptozotocin-nicotinamide generated oxidative stress induced diabetic rats. Chem Biol Interact 195:43–51
Szapiel SV, Elson NA, Fulmer JD, Hunninghake GW, Crystal RG (1979): Bleomycin-induced interstitial pulmonary disease in the nude, athymic mouse. Am Rev Respir Dis 120, 893-9
Tahir M, Rehman MU, Lateef A, Khan AQ, Khan R, Qamar W, O’Hamiza O, Ali F, Hasan SK, Sultana S (2013) Diosmin abrogates chemically induced hepatocarcinogenesis via alleviation of oxidative stress, hyperproliferative and inflammatory markers in murine model. Toxicol Lett 220:205–218
Tomita M, Okuyama T, Katsuyama H, Miura Y, Nishimura Y, Hidaka K, Otsuki T, Ishikawa T (2007) Mouse model of paraquat-poisoned lungs and its gene expression profile. Toxicology 231:200–209
Tortorelli M, Hernandez D, Vázquez GR, Salibián A (1990) Effects of paraquat on mortality and cardiorespiratory function of catfish fry Plecostomus commersoni. Arch Environ Contam Toxicol 9:523–529
Wang Y, Zhou M, Lu Y, Yu A, Li J (2017) Protective effect of 5-aminosalicylic acid on the kidney of paraquat poisoning rats by Nrf2-ARE signal pathway. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 29:961–966
Wu W-P, Lai M-N, Lin C-H, Li Y-F, Lin C-Y, Wu M-J (2014) Addition of immunosuppressive treatment to hemoperfusion is associated with improved survival after paraquat poisoning: a nationwide study. PLoS One 9:e87568
Xu S, Hu H, Jiang Z, Tang S, Zhou Y, Sheng J, Chen J, Cao Y (2015) APACHE score, Severity Index of Paraquat Poisoning, and serum lactic acid concentration in the prognosis of paraquat poisoning of Chinese Patients. Pediatr Emerg Care 31:117–121
Yang C, Song HW, Liu W, Dong XS, Liu Z (2018) Protective effects of chymostatin on paraquat-induced acute lung injury in mice. Inflammation 41:122–133
Yao R, He Y, Zeng Z, Liang Z, Cao Y (2015) Protective effect of adiponectin on paraquat-induced pulmonary fibrosis in mice. Mol Cell Toxicol 11:247–255
Zerin T, Kim Y-S, Hong S-Y, Song H-Y (2012) Protective effect of methylprednisolone on paraquat-induced A549 cell cytotoxicity via induction of efflux transporter, P-glycoprotein expression. Toxicol Lett 208:101–107
Zhu Y, Deng G, Ji A, Yao J, Meng X, Wang J, Wang Q, Wang R (2017) Porous Se@SiO2 nanospheres treated paraquat-induced acute lung injury by resisting oxidative stress. Int J Nanomedicine 12:7143–7152
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This paper is issued from the Pharm.D thesis of Sirus Mirzaee and was financially supported by the Toxicology Research Center (Grant Number: TRC-9607) of AJUMS.
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Mirzaee, S., Mansouri, E., Shirani, M. et al. Diosmin ameliorative effects on oxidative stress and fibrosis in paraquat-induced lung injury in mice. Environ Sci Pollut Res 26, 36468–36477 (2019). https://doi.org/10.1007/s11356-019-06572-2
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DOI: https://doi.org/10.1007/s11356-019-06572-2