Protective and Therapeutic Effect of Molsidomine on Bleomycin-Induced Lung Fibrosis in Rats
- 429 Downloads
We aimed to investigate the preventive and treatment effect of molsidomine (MOL) on bleomycin (BLC)-induced lung injury in rats. Rats were assigned into groups as follows: control group; MOL group, 10 mg/kg MOL was continued orally for 29 day; BLC group, a single intratracheal injection of BLC (2.5 mg/kg), MOL+BLC-preventive group, 10 mg/kg MOL was administered 1 day before the intratracheal BLC injection and continued for 14 days; BLC+MOL-treatment group 10 mg/kg MOL was given on 14th day after the intratracheal BLC injection and continued until sacrifice. All animals were sacrificed on 29th day after BLC administration. The semiquantitative histopathological assessment, tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), total antioxidant status (TAS), total oxidant status (TOS), myeloperoxidase (MPO), and oxidative stress index (OSI) were measured. BLC-provoked histological changes were significantly detected compared to the control group. MOL restored these histological damages in different quantity in the treatment and preventive groups. BLC administration significantly decreased levels of GSH and TAS when compared to controls and these reductions was significantly ameliorated by MOL given prophylactic setting. However, therapeutic MOL administration significantly increased the TAS level decreased by BLC. The levels of MDA, MPO, and TOS were significantly increased with BLM, and these augmentations of MDA and TOS were significantly reduced by MOL given prophylactic setting. Furthermore, the OSI was higher in the BLC group, and this increase was reversed by the MOL administration before and after BLC treatment. In this study, both protective and therapeutic effects of MOL against BLC-induced lung fibrosis were demonstrated for the first time.
KEY WORDSbleomycin pulmonary fibrosis inflammation molsidomine idiopathic pulmonary fibrosis
Conflict of Interest
The authors have no conflict of interest to declare. This work has not been supported by grant from any funding agency in the public, commercial, or not-for-profit sectors.
- 1.Raghu, G., H.R. Collard, J.J. Egan, F.J. Martinez, J. Behr, K.K. Brown, T.V. Colby, J.F. Cordier, K.R. Flaherty, J.A. Lasky, et al. 2011. An official ATS/ERS/JRS/ALAT statement: Idiopathic pulmonary fibrosis: Evidence-based guidelines for diagnosis and management. American Journal of Respiratory and Critical Care Medicine 183: 788–824.PubMedCrossRefGoogle Scholar
- 5.Mata, M., A. Ruíz, M. Cerdá, M. Martinez-Losa, J. Cortijo, F. Santangelo, A. Serrano-Mollar, A. Llombart-Bosch, and E.J. Morcillo. 2003. Oral N-acetylcysteine reduces bleomycin-induced lung damage and mucin Muc5ac expression in rats. European Respiratory Journal 22(6): 900–905.Google Scholar
- 6.Sogut, S., H. Ozyurt, F. Armutcu, et al. 2004. Erdosteine prevents bleomycin-induced pulmonary fibrosis in rats. European Journal of Pharmacology 494: 213–220.Google Scholar
- 7.Yildirim, Z., Y. Turkoz, M. Kotuk, et al. 2004. Effects of aminoguanidine and antioxidant erdosteine on bleomycin-induced lung fibrosis in rats. Nitric Oxide 11: 156–165.Google Scholar
- 8.Yildirim, Z., M. Kotuk, H. Erdogan, M. Iraz, M. Yagmurca, I. Kuku, and E. Fadillioglu. 2006. Preventive effect of melatonin on bleomycin-induced lung fibrosis in rats. Journal of Pineal Research 40: 27–33.Google Scholar
- 9.Iraz, M., H. Erdogan, M. Kotuk, M. Yagmurca, T. Kilic, H. Ermis, E. Fadillioglu, and Z. Yildirim. 2006. Ginkgo biloba inhibits bleomycin-induced lung fibrosis in rats. Pharmacological Research 53: 310–316.Google Scholar
- 39.Hong-ping, X.I.A., H. Guo-ying, Z.H.U. Jian-xing, and S.U.N. Bo. 2008. Effect of inhalation of nebulized NO donor substance on acute hypoxic lung injury in newborn piglets. Chinese Medical Journal 121(17): 1622–1626.Google Scholar
- 42.Cao, L., L.L. Qian, Y.R. Zhu, C.B. Guo, X.H. Gong, and B. Sun. 2003. Regulation of activity of nuclear factor-kappa B and activator protein-1 by nitric oxide, surfactant and glucocorticoids in alveolar macrophages from piglets with acute lung injury. Acta Pharmacologica Sinica 24: 1316–1323.PubMedGoogle Scholar