The effects of erdosteine on lung injury induced by the ischemia-reperfusion of the hind-limbs in rats (original) (raw)
Erdosteine ameliorates the harmful effects of ischemia-reperfusion injury on the liver of rats
Acta cirurgica brasileira, 2017
To investigate the potential protective effects of erdosteine against the harmful effects of ischemia-reperfusion injury on the liver in an experimental rat model. Forty rats were divided into 4 groups. In the sham group, only the hepatic pedicle was mobilized. No other manipulation or treatment was performed. In the other groups, ischemia was achieved by clamping the hepatic pedicle for 60 min. After that, 90 min reperfusion was provided. In the control group, no treatment was given. In the perioperative treatment group, 100 mg/kg erdosteine was administered 2 hours before ischemia induction. In the preoperative treatment group, 100 mg/kg/day erdosteine was administered daily for ten days before the operation. At the end of the procedures, blood and liver samples were obtained for biochemical and histopathological assessment. Treatment with erdosteine ameliorated the histopathological abnormalities when compared with the control group. Furthermore, this treatment significantly decr...
Effects of Erdosteine in Experimental Sepsis Model in Rats
Hong Kong Journal of Emergency Medicine, 2011
Objective Erdosteine is a mucolytic agent that is known to possess antioxidant effects. This study investigated the effects of erdosteine on endothelin-1 (ET-1) levels and oxidative stress parameters superoxide dismutase (SOD) and malondialdehyde (MDA) in a rat sepsis model. Methods Four groups of Wistar albino rats (n=8 per group) were randomly allocated to the following groups: sham (group 1), sepsis (group 2), erdosteine control (group 3) and a sepsis group pretreated with erdosteine (group 4). Sepsis was induced using E. Coli ATCC 25922 inoculation. Serum ET-1, liver tissue SOD and MDA levels were determined in all groups. Results ET-1 levels were significantly higher in group 2 compared to groups 1, 3 and 4 (p<0.001, p=0.002 and p<0.001, respectively). Similarly, MDA levels in groups 1, 3 and 4 were significantly lower relative to group 2 (p<0.001, p=0.022 and p=0.010, respectively). Additionally, SOD activities in these same three groups were found to be significantly...
The protective effect of erdosteine on short-term global brain ischemia/reperfusion injury in rats
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2009
Experimental studies have demonstrated that free radicals play a major role on neuronal injury during ischemia/reperfusion (I/R) in rats. Erdosteine is a thioderivative endowed with mucokinetic, mucolytic and free-radical-scavenging properties. The aim of the present study was to investigate the effect of erdosteine treatment against short-term global brain ischemia/reperfusion injury in rats. The study was carried out on Wistar rats divided into four groups. (i) Control group, (ii) ischemia/reperfusion group, (iii) ischemia/reperfusion + erdosteine group, and (iv) erdosteine group. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities as well as thiobarbituric acid reactive substances (TBARSs) and nitric oxide (NO) levels were analysed in erythrocyte and plasma of rats. Plasma NO levels were significantly higher in the ischemia/reperfusion group than the other groups. The activities of SOD and GSH-Px were decreased, while TBARS levels increased in the ischemia/reperfusion group compared to other groups in both plasma and erythrocyte. The erythrocyte CAT activity was higher in erdosteine group and there was a statistically significant increase, when compared with the erdosteine plus ischemia/reperfusion group. By treating the rats with erdosteine, the depletion of endogenous antioxidant enzymes (SOD, CAT, GSH-Px) and increase of TBARS and NO levels were prevented. This study, therefore, suggests that erdosteine reduces parameters of oxidative stress is well supported by the data.
Journal of Surgical …, 2008
Background. The aim of this study was to clarify whether levosimendan could prevent lung tissue injury from limb ischemia/reperfusion. Methods. The common femoral arteries of 50 New Zealand white rabbits, both male and female, each weighing about 3 kg, were clamped and 1 h of ischemia followed by 4 h of reperfusion. In an attempt to decrease reperfusion injury, the rabbits were given levosimendan in Group A. In Group B, iloprost was infused at the same period. A similar value of saline solution was given in the control group, Group C correspondingly. Levosimendan and iloprost were given together the Group E, and Group D was sham group without medication and ischemia. Blood pH, pO2, pCO2, HCO3, Na, K, creatine phosphokinase, lactate dehydrogenase values were determined at the end of the reperfusion period. Malondialdehyde (MDA) was measured in plasma and lung as an indicator of free radicals. Hemodynamics parameters were noted for each group. After the procedure, left lung tissues were taken for histopathologic study. Results. Blood PO2 and HCO3 levels were significantly higher (P < 0.05) and creatine phosphokinase, lactate dehydrogenase, and MDA levels were significantly lower (P < 0.05) in Groups A, B, D, and E compared with Group C. Similarly, the MDA levels in the lung tissue and plasma levels were significantly lower in the treatment groups compared with the control group (P < 0.05). Lung damage was significantly higher in Group C. There was no significant difference between groups in other parameters. Conclusions. The results suggest that levosimendan and iloprost are useful for attenuating oxidative lung damage occurring after a period of limb ischemia/reperfusion.
European Journal of Cardio-Thoracic Surgery, 2006
Objective: Increased microvascular permeability and extravasation of inflammatory cells are key events in ischemia-reperfusion (IR) injury. We hypothesized that edaravone, a free radical scavenger, is able to attenuate IR lung injury by decreasing oxidative stress and phospholipase A 2 (PLA 2 ) activation, which otherwise may lead to lung injury through PAF receptor (PAF-R) activation. Methods: We used an isolated rat lung model. Five groups were defined (n = 7, each): in the sham and vehicle group, lungs were immediately washed after thoracotomy or perfused for 2 h without an ischemic period, respectively. In the ischemic groups, 10 mg/kg of MCI-186 (edavorane group), 1 mg/kg of PAF-R inhibitor (ABT-491 group) or saline (control group) were i.v. administered 20 min before harvest. Lungs were flushed with LPD solution, stored at 4 8C for 18 h, and reperfused for 2 h. Results: Compared to vehicle group, IR significantly decreased the PO 2 level and increased the wet-to-dry ratio, proteins in bronchoalveolar lavage (BAL), and myeloperoxidase (MPO) activity in the control group, while edaravone treatment maintained the PO 2 similar to the vehicle group and significantly reduced edema formation and neutrophil extravasation. Consistently, IR significantly increased lipid peroxidation, cytosolic-PLA 2 activity mainly via alveolar macrophages, soluble-PLA 2 activity, leukotriene B 4 , and PAF-R expression in control lungs, together with a decreased PAF acetylhydrolase (PAF-AH) activity. Edaravone significantly reduced all of these, but increased PAF-AH activity. Furthermore, pharmacological inhibition of the PAF-R attenuated IR injury resembling edaravone action. Conclusion: Edaravone attenuates lung IR injury by suppressing oxidative damage and PLA 2 activation, which otherwise partially mediates edema formation and neutrophil extravasation through PAF-R activation. #
Effects of erdosteine on bleomycin-induced lung fibrosis in rats
Molecular and Cellular Biochemistry, 2006
This study was designed to examine the effects of erdosteine on bleomycin (BLM)-induced lung fibrosis in rats. Thirty-three Sprague–Dawley rats were divided randomly into three groups, bleomycin alone (BLM), bleomycin + erdosteine (BLM + ERD), and saline alone (control). The BLM and BLM + ERD groups, were given 2.5 mg/kg BLM intratracheally. The first dose of oral erdosteine (10 mg/kg/day) in the BLM + ERD group was started 2 days before BLM administration and continued until animals were sacrificed. Animals were sacrificed 14 days after intratracheal instillation of BLM. The effect of erdosteine on pulmonary fibrosis was studied by analysis of bronchoalveolar lavage (BAL) fluid, histopathology, and biochemical measurements of lung tissue superoxide dismutase (SOD) and glutathione (GSH) as antioxidants, malondialdehyde (MDA) as an index for lipid peroxidation, and nitrite/nitrate levels. Bleomycin-induced lung fibrosis as determined by lung histology was prevented with erdosteine (grades of fibrosis were 4.9, 2.3, and 0.2 in BLM, BLM + ERD, and control groups, respectively). Erdosteine also prevented bleomycin-induced increase in MDA (MDA levels were 0.50 ± 0.15, 0.11 ± 0.02, and 0.087± 0.03 nmol/mg protein in BLM, BLM + ERD, and control groups, respectively) and nitrite/nitrate (nitrite/nitrate levels were 0.92 ± 0.06, 0.60 ± 0.09, and 0.56± 0.1 μmol/mg protein in BLM, BLM + ERD, and control groups respectively) levels. Bleomycin-induced decrease in GSH and SOD levels in the lung tissue also prevented by erdosteine [(GSH levels were 213.5 ± 12.4, 253.2± 25.2, and 287.9± 34.4 nmol/mg protein) (SOD levels were 1.42± 0.12, 1.75± 0.17, and 1.89± 0.09 U/mg protein) in BLM, BLM + ERD, and control groups respectively]. Erdosteine prevented bleomycin-induced increases in total cell number and neutrophil content of the BAL fluid. In conclusion, oral erdosteine is effective in prevention of BLM-induced lung fibrosis in rats possibly via the repression of neutrophil accumulation, inhibition of lipid peroxidation, and maintenance of antioxidant and free radical scavenger properties.
European Journal of Pharmacology, 2009
Erythropoietin (Epo) was recently defined as an endogenous agent with more than hematopoietic functions. Previously we explored the potential of this agent to ameliorate lung ischemia-reperfusion (I/R) injury. The present study aims to determine the optimal dose and timing of administration for improving lung injury, and to further investigate the mechanisms by which Epo ameliorates lung I/R injury. The left lungs of Sprague-Dawley rats underwent 90 min ischemia and 120 min reperfusion. Firstly, animals in different groups were intraperitoneally injected with various doses of recombined human erythropoietin (rhEpo) 24 h prior to operation, 2 h prior to operation, or after the onset of reperfusion. Pulmonary myeloperoxidase (MPO) activity and malondialdehyde (MDA) content were evaluated. Treatment with 3 KU/kg rhEpo 2 h prior to operation was optimal for attenuating pulmonary MPO activity and MDA content. With such treatment, ultrastructural changes of pneumocytes were observed, and the pneumocyte apoptosis index was also determined by terminal dUTP nick-end labeling method. The plasma concentrations of tumor necrosis factor (TNF)-α and matrix metalloproteinase (MMP)-9 were evaluated by enzyme-linked immunosorbent assay, and pulmonary expression by immunohistochemistry. When pretreated with rhEpo, the pneumocyte ultrastructure was predominantly maintained and the pulmonary apoptosis index was markedly reduced. In comparison with untreated animals, in treated animals the plasma concentrations of TNF-α and MMP-9 were significantly decreased, and their expression in lung tissue was markedly reduced as well. The results indicated that Epo potently protected against lung I/R injury by inhibiting systemic and local expression of TNF-α and MMP-9.
Life Sciences, 2005
Ischemic preconditioning (IP) has been shown to protect the lung against ischemia-reperfusion (I/R) injury. Although the production of reactive oxygen species (ROS) has been postulated to play a crucial role in I/R injury, the sources of these radicals in I/R and the mechanisms of protection in IP remain unknown. Since it was postulated that deamination of endogenous and exogenous amines by semicarbazide-sensitive amine oxidase (SSAO) in tissue damage leads to the overproduction of hydrogen peroxide (H 2 O 2), we investigated the possible contribution of tissue SSAO to excess ROS generation and lipid peroxidation during I/R and IP of the lung. Male Wistar rats were randomized into 6 groups: control lungs were subjected to 30 min of perfusion in absence and presence of SSAO inhibitor, whereas the lungs of the I/R group were subjected to 2 h of cold ischemia following the 30 min of perfusion in absence and presence of SSAO inhibitor. IP was performed by two cycles of 5 min ischemia followed by 5 min of reperfusion prior to 2 h of hypothermic ischemia in absence and presence of SSAO inhibitor. Lipid peroxidation, reduced (GSH) and oxidized (GSSG) glutathione levels, antioxidant enzyme activities, SSAO activity, and H 2 O 2 release were determined in tissue samples of the study groups. Lipid peroxidation, glutathione disulfide (GSSG) content, SSAO activity and H 2 O 2 release were increased in the I/R group, whereas GSH content, GSH / GSSG ratio and antioxidant enzyme activities were decreased. SSAO activity, H 2 O 2 release, GSSG content and lipid peroxidation were markedly decreased in the IP group, whereas GSH content, GSH / GSSG ratio and antioxidant enzyme activities were significantly increased. SSAO activity was found to be positively correlated with H 2 O 2 production in all study groups. Increased lipid peroxidation, SSAO activity, GSSG and H 2 O 2 contents as well as decreased GSH and antioxidant enzyme levels in I/R returned to their basal levels when IP and SSAO inhibition were applied together. The present study suggests that application of IP and SSAO inhibition together may be more effective than IP alone against I/R injury in the lung.
Dipyridamole Reduces Lung Injury in a Rat Lung Ischemia and Reperfusion Model
Research Square (Research Square), 2024
Background: In this study, the effect of Dipyridamole (DIP) on lung tissue in lung ischemia/reperfusion (I/R) injury in rats was investigated. Methods: A total of 24 Wistar rats were divided into four equal groups with six rats in each group: Group Sham, Group I/R (ischemia/reperfusion), and Group I/R+ 10mg/kg DIP, Group I/R+ 100mg/kg DIP. 45 minutes of ischemia and 120 minutes of reperfusion were applied. Results: TNF-α value was decreased in Groups 10mg/kg DIP and I/R+ 100mg/kg DIP compared to Group I/R. TNF-α value value was lower in Groups 10mg/kg DIP and 100mg/kg DIP. The difference in TNF-α value was statistically signi cant between the groups (p=0.002). Statistically signi cant results were observed between Group I/R-DIP 100 mg/kg and Group I/R for TNF-α. (p=0.038). MDA value in the blood was higher in Group I/R than in Group Sham. MDA value was decreased in Groups 10mg/kg DIP and 100mg/kg DIP compared to Group I/R. However, the difference in MDA value was not statistically signi cant between the groups (p=0.071). Catalase level in the blood was higher in Group I/R than Group Sham.). The difference in CAT activity was statistically signi cant between the groups (p=0.025). Statistically signi cant results were observed between Group I/R-DIP 100 and Group I/R for CAT. (p=0.047). According to histopathological examination, lung tissue neutrophil in ltration, pulmonary edema, interstitial edema, alveolar hemorrhage and total score levels were signi cantly higher in Group I/R than Groups I/R-10mg/kg DIP and I/R-100mg/kg DIP(p=0.02, p=0.03, p=0.01, respectively, p=0.03 and p=0.01). Lung tissue pulmonary edema, interstitial edema, neutrophil in ltration, alveolar hemorrhage and total score levels were signi cantly lower in Group 10mg/kg DIP compared to Group I/R (p=0.03, p=0.01, p=0.02, p=0.03 and p=0.01, respectively). ). Lung tissue pulmonary edema, interstitial edema, neutrophil in ltration, alveolar hemorrhage and total score levels were signi cantly lower in Group I/R-100mg/kg DIP compared to Group I/R (p=0.009, p=0.002, p=0.001, p=0.002 and p=0.002, respectively). ). Conclusion: Lung tissue may be affected by ischemia/reperfusion injury, and this damage can be reversed with the use of dipyridamole.