Cromolyn Sodium Attenuates Paraquat-Induced Lung Injury by Modulation of Proinflammatory Cytokines

Abstract

The current study aimed to investigate the effects of Cromolyn Sodium (CS) on proinflammatory cytokines in Paraquat (PQ)-induced lung damage in rat. Animals were randomly divided into 5 groups. Group 1 and 2 received nebulized vehicle and CS (8 mg/kg) for 3 consecutive weeks, respectively. Group 3 was treated with single oral dose of PQ (40 mg/kg). Groups 4 and 5 were PQ groups which received nebulized CS (6 and 8 mg/kg/day, respectively) from 1 week before to 2 weeks after PQ administration. Finally, the animals were scarified and the changes of hydroxyproline (HP) and histology were evaluated in lung tissue. In addition, IL-1β, TNF-α and IL-8 levels were determined in serum samples. The results showed that lung HP level as well as IL-1β, TNF-α and IL-8 were significantly lower in the CS treated rats as compared to PQ group. The best response, however, was observed with the 8 mg/kg of CS as confirmed by histology findings. This study suggests that CS may prevent progression of PQ-induced lung damage by decreasing of inflammatory cytokines.

Key words

cromolyn sodium - paraquat - proinflammatory cytokines

• References

• 1 Chen Y, Nie YC, Luo YL. et al. Protective effects of naringin against paraquat-induced acute lung injury and pulmonary fibrosis in mice. Food Chem Toxicol 2013; 58: 133-140
• 2 Pourgholamhossein F, Sharififar F, Rasooli R. et al. Thymoquinone effectively alleviates lung fibrosis induced by paraquat herbicide through down-regulation of pro-fibrotic genes and inhibition of oxidative stress. Environ Toxicol Pharmacol 2016; 45: 340-345
• 3 Sun Y, Zhang J, Yan Y. et al. The protective effect of C-phycocyanin on paraquat-induced acute lung injury in rats. Environ Toxicol Pharmacol 2011; 32: 168-174
• 4 Charão MF, Baierle M, Gauer B. et al. Protective effects of melatonin-loaded lipid-core nanocapsules on paraquat-induced cytotoxicity and genotoxicity in a pulmonary cell line. Mutat Res Genet Toxicol Environ Mutagen 2015; 784: 1-9
• 5 Amirshahrokhi K. Anti-inflammatory effect of thalidomide in paraquat-induced pulmonary injury in mice. Int Immunopharmacol 2013; 17: 210-215
• 6 Suntres ZE. Role of antioxidants in paraquat toxicity. Toxicology 2002; 180: 65-77
• 7 Rocco PR, Souza AB, Faffe DS. et al. Effect of corticosteroid on lung parenchyma remodeling at an early phase of acute lung injury. Am J Respir Crit Care Med 2003; 168: 677-684
• 8 Dinis-Oliveira RJ, Sousa C, Remião F. et al. Sodium salicylate prevents paraquat-induced apoptosis in the rat lung. Free Radic Biol Med 2007; 43: 48-61
• 9 Dinis-Oliveira RJ, Pontes H, Bastos ML. et al. An effective antidote for paraquat poisonings: the treatment with lysine acetylsalicylate. Toxicology 2009; 255: 187-193
• 10 Hei Z-Q, Gan X-L, Luo G-J. et al. Pretreatment of cromolyn sodium prior to reperfusion attenuates early reperfusion injury after the small intestine ischemia in rats. World J Gastroenterol 2007; 13: 5139-5146
• 11 Hu YJ, Liu Y, Sun TQ. et al. Binding of anti-inflammatory drug cromolyn sodium to bovine serum albumin. Int J Biol Macromol 2006; 39: 280-285
• 12 Kanellakis P, Ditiatkovski M, Kostolias G. et al. A profibrotic role for interleukin-4 in cardiac pressure overload. Cardiovasc Res 2012; 95: 75-85
• 13 Veerappan A, O’Connor NJ, Brazin J. et al. Mast cells: a pivotal role in pulmonary fibrosis. DNA Cell Biol 2013; 32: 206-218
• 14 Toygar M, Aydin I, Agilli M. et al. The relation between oxidative stress, inflammation, and neopterin in the paraquat-induced lung toxicity. Hum Exp Toxicol 2015; 34: 198-204
• 15 Khalighi Z, Rahmani A, Cheraghi J. et al. Perfluorocarbon attenuates inflammatory cytokines, oxidative stress and histopathologic changes in paraquat-induced acute lung injury in rats. Environ Toxicol Pharmacol 2016; 42: 9-15
• 16 Edwards CA, O’Brien WDJ. Modified assay for determination of hydroxyproline in a tissue hydrolyzate. Clin Chim Acta 1980; 104: 161-167
• 17 Larki-Harchegani A, Hemmati AA, Arzi A. et al. Evaluation of the effects of caffeic acid phenethyl ester on prostaglandin E₂ and two key cytokines involved in bleomycin-induced pulmonary fibrosis. Iran J Basic Med Sci 2013; 16: 850-857
• 18 Ball SL, Mann DA, Wilson JA. et al. The role of the fibroblast in inflammatory upper airway conditions. Am J Pathol 2016; 186: 225-233
• 19 Xie H, Wang R, Tang X. et al. Paraquat-induced pulmonary fibrosis starts at an early stage of inflammation in rats. Immunotherapy 2012; 4: 1809-1815
• 20 Hemmati AA, Nazari Z, Motlagh ME. et al. The role of sodium cromolyn in treatment of paraquat-induced pulmonary fibrosis in rat. Pharmacol Res 2002; 46: 229-234
• 21 Erroi A, Bianchi M, Ghezzi P. The pneumotoxicant paraquat potentiates IL-1 and TNF production by human mononuclear cells. Agents Actions 1992; 36: 66-69
• 22 Aires RD, Capettini LSA, Silva JF. et al. Paraquat poisoning induces TNF-alpha-dependent iNOS/NO mediated hyporesponsiveness of the aorta to vasoconstrictors in rats. PLoS One 2013; 8: 1-13
• 23 Mukhopadhyay S, Hoidal JR, Mukherjee TK. Role of TNFα in pulmonary pathophysiology. Respir Res 2006; 7: 1-9
• 24 Lee IT, Yang CM. Role of NADPH oxidase/ROS in pro-inflammatory mediators-induced airway and pulmonary diseases. Biochem Pharmacol 2012; 84: 581-590
• 25 He X, Wang L, Szklarz G. Resveratrol inhibits paraquat-induced oxidative stress and fibrogenic response by activating the nuclear factor erythroid 2-related factor 2 pathway. J Pharmacol Exp Ther 2012; 342: 81-90
• 26 Allen TC, Kurdowska A. Interleukin 8 and acute lung injury. Arch Pathol Lab Med 2014; 138: 266-269
• 27 Zhu YM, Webster SJ, Flower D. et al. Interleukin-8/CXCL8 is a growth factor for human lung cancer cells. Br J Cancer 2004; 91: 1970-1976
• 28 Car BD, Meloni F, Luisetti M. et al. Elevated IL-8 and MCP-1 in the bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis. Am J Respir Crit Care Med 1994; 149: 655-659
• 29 Larki A, Hemmati AA, Arzi A. et al. Regulatory effect of caffeic acid phenethyl ester on type I collagen and interferon-gamma in bleomycin-induced pulmonary fibrosis in rat. Res Pharm Sci 2013; 8: 243-252