Protective and Therapeutic Effect of Molsidomine on Bleomycin-Induced Lung Fibrosis in Rats

Abstract

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.

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“…Lung inflammation is considered to be a major contributing factor in the induction of pulmonary fibrosis 14,15,33 . ROS such as superoxide anion, hydrogen peroxide, and hydroxyl radical are reported as mediators of lung inflammatory processes 33 .…”

“…ROS such as superoxide anion, hydrogen peroxide, and hydroxyl radical are reported as mediators of lung inflammatory processes 33 .…”

“…BLM has also been reported to result in depletion of endogenous antioxidant defenses thereby increasing the risk of oxidant mediated tissue injury 33,50 .…”

“…Several studies suggest that a number of antioxidant and detoxification enzymes as MnSOD, catalase, glutamate cysteine ligase, thioredoxin, glutaredoxin, and heme-oxygenase 1 are low/ absent in the fibrotic lesions of pulmonary fibrosis 33,51 . As in line with the previous reports in the study similar reduction in the activity of antioxidant enzymes were observed (p<0.05) in animals that were induced with BLM as compared to group I animals.…”

Protective effects of molsidomine against doxorubicin-induced renal damage in rats

“…The clinical applications of MLS in the field of cardiology are well established, especially relating to the symptomatic treatment of angina [6][7][8][9]. Apart from these properties, it is also well established that MLS exerts antioxidant and anti-inflammatory effects [32][33][34].…”