The preventive role of levosimendan against bleomycin-induced pulmonary fibrosis in rats

Background In this study, the effects of levosimendan used in the treatment of acute congestive heart failure upon pulmonary fibrosis in rats induced with bleomycin (BL) were analyzed. Methods A total of 33 male Sprague-Dawley type rats were categorized into five groups randomly. About 2.5 U/kg BL was intratracheally administered to the rats in the BL, BL + L1, BL + L2, and BL + L3 groups, and 0.9% saline was intratracheally administered at the same rate to the control group. 0.3, 1, and 3 mg/kg levosimendan was intraperitoneally administered to the BL + L1, BL + L2, and BL + L3 groups, respectively. Blood and tissue samples were taken from the rats euthanized to determine the changes in erythrocyte enzyme activities and to conduct histopathological evaluations after 14 days. With values between 0 and 3, histopathological scoring damage was assessed by the presence of inflammation and fibrosis in a semiquantitative manner. Results Compared with those in the C group, glutathione reductase (GR) and Catalase (CAT) enzymes decreased in the BL group; compared with that in the BL group, GR increased in the BL + L1 and BL + L3 groups, 6-phosphogluconate dehydrogenase (6PGD) increased in the BL + L3 group, and CAT increased in the BL + L2 and BL + L3 groups (p < 0.05). In the histopathological evaluation, fibrosis occurred in all rats in the BL group, and tissue damage was noticed to be generally less in the BL + L1, BL + L2, and BL + L3 groups (p < 0.001). Conclusions The results obtained from biochemical and histopathological evaluations indicate that levosimendan had an anti-fibrotic effect without a dose-dependent response on pulmonary fibrosis. © 2015 Institute of Pharmacology, Polish Academy of Sciences.