Protective role of erdosteine pretreatment on oleic acid–induced acute lung injury

Erdem, Ayşen; Gedikli, Esra; Yersal, Nilgün; Karaismailoğlu, Serkan; Müftüoğlu, Sevda; Fadıllıoğlu, Ersin; Tuncer, Meltem

doi:10.1016/j.jss.2017.02.061

Cited by 12 publications

(7 citation statements)

References 28 publications

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“…Similar to previous studies [ 24 , 48 ], MDA levels were found to be high in lung tissues in the present work and OA caused damage to lung cells. ROS such as superoxide anion radical, H 2 O 2 , and hydroxyl radical cause the oxidative breakdown of the polyunsaturated fatty acids of cell membranes, a process known as lipid peroxidation [ 49 ], and MDA is formed in the end.…”

Section: Discussionsupporting

confidence: 92%

Effects of tocilizumab and dexamethasone on the downregulation of proinflammatory cytokines and upregulation of antioxidants in the lungs in oleic acid-induced ARDS

et al. 2022

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Background Acute respiratory distress syndrome (ARDS) is a life-threatening disease caused by the induction of inflammatory cytokines and chemokines in the lungs. There is a dearth of drug applications that can be used to prevent cytokine storms in ARDS treatment. This study was designed to investigate the effects of tocilizumab and dexamethasone on oxidative stress, antioxidant parameters, and cytokine storms in acute lung injury caused by oleic acid in rats. Methods Adult male rats were divided into five groups: the CN (healthy rats, n = 6), OA (oleic acid administration, n = 6), OA + TCZ-2 (oleic acid and tocilizumab at 2 mg/kg, n = 6), OA + TCZ-4 (oleic acid and tocilizumab at 4 mg/kg, n = 6), and OA + DEX-10 (oleic acid and dexamethasone at 10 mg/kg, n = 6) groups. All animals were euthanized after treatment for histopathological, immunohistochemical, biochemical, PCR, and SEM analyses. Results Expressions of TNF-α, IL-1β, IL-6, and IL-8 cytokines in rats with acute lung injury induced by oleic acid were downregulated in the TCZ and DEX groups compared to the OA group (P < 0.05). The MDA level in lung tissues was statistically lower in the OA + TCZ-4 group compared to the OA group. It was further determined that SOD, GSH, and CAT levels were decreased in the OA group and increased in the TCZ and DEX groups (P < 0.05). Histopathological findings such as thickening of the alveoli, hyperemia, and peribronchial cell infiltration were found to be similar when lung tissues of the TCZ and DEX groups were compared to the control group. With SEM imaging of the lung tissues, it was found that the alveolar lining layer had become indistinct in the OA, OA + TCZ-2, and OA + TCZ-4 groups. Conclusions In this model of acute lung injury caused by oleic acid, tocilizumab and dexamethasone were effective in preventing cytokine storms by downregulating the expression of proinflammatory cytokines including TNF-α, IL-1β, IL-6, and IL-8. Against the downregulation of antioxidant parameters such as SOD and GSH in the lung tissues caused by oleic acid, tocilizumab and dexamethasone upregulated them and showed protective effects against cell damage.

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Section: Discussionsupporting

confidence: 92%

Effects of tocilizumab and dexamethasone on the downregulation of proinflammatory cytokines and upregulation of antioxidants in the lungs in oleic acid-induced ARDS

et al. 2022

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“…In line with our findings, a previous investigation reported that administration of oleic acid (50 µL, i.v.) to rats resulted in intra-alveolar edema, increased presence of macrophages in intra-alveolar locations, and a significant rise in neutrophil counts in intra-alveolar and interstitial areas, notably surrounding the congestive capillaries (Erdem et al 2017 ). Another study has also stated that receiving oleic acid (by continuous infusion of 0.2 mL/kg) caused inflammation, edema, hemorrhage, septal necrosis, and collapsed alveoli in the lung tissue of large white pigs (Borges et al 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic effects of minocycline on oleic acid-induced acute respiratory distress syndrome (ARDS) in rats

Razavi

Naraki

Hosseinzadeh

2023

Naunyn-Schmiedeberg's Arch Pharmacol

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Acute respiratory distress syndrome (ARDS) is a serious intensive care condition. Despite advances in treatment over the previous few decades, ARDS patients still have high fatality rates. Thus, more research is needed to improve the outcomes for people with ARDS. Minocycline is an antibiotic with antioxidant, anti-inflammatory, and anti-apoptotic effects. In the current investigation, the therapeutic effects of minocycline on oleic acid-induced ARDS were evaluated. Male rats were classified into 6 groups, 1. control (normal saline), 2. oleic acid (100 µL, i.v.), 3–5. oleic acid + minocycline (50, 100, 200 mg/kg, i.p.), and 6. minocycline (200 mg/kg, i.p.) alone. Twenty-four hours after the oleic acid injection, the lung tissue is isolated, weighed, and the middle part of the right lung is immediately placed in the freezer, while the middle part of the left lung is placed in formalin and sent to the laboratory for pathology testing. Then, the amounts of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), cytokines (interleukin-1 beta (IL-1β), tumor necrosis factor-α (TNF-α)), B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X (Bax), and cleaved caspase-3 were determined in lung tissue. Administration of oleic acid increased emphysema, inflammation, vascular congestion, hemorrhage, MDA amount, Bax/Bcl-2 ratio, cleaved caspase-3, IL-1β, TNF-α levels, and decreased GSH, SOD, and CAT levels in comparison with the control group. The administration of minocycline could significantly reduce pathological and biochemical alterations induced by oleic acid. Minocycline has a therapeutic effect on oleic acid-induced ARDS through antioxidant, anti-inflammatory, and anti-apoptotic properties. Graphical abstract

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“…Полученные результаты вероятно связаны с тем, что активная SH группа метаболита эрдостеина способна блокировать активные формы кислорода [23]. Это предположение подтверждается данными исследований, проведенных на экспериментальных моделях и продемонстрировавших, что эрдостеин уменьшает повреждение легочной ткани, вызванное окислительным стрессом [24][25][26] за счет ингибирования синтеза воспалительных белков [27]. В другом исследовании, посвященном влиянию эрдостеина на перекисное окисление липидов у курящих людей без патологии бронхолегочной системы, авторы выявили, что один месяц приема изучаемого препарата значительно снижал концентрацию тиобарбитуровых кислот (маркер перекисного окисления), образующихся в том числе после вдыхания дыма [28].…”

Section: антиоксидантные и противовоспалительные свой ства эрдостеинаunclassified

Clinical aspects of the use of erdosteine in respiratory diseases

Карнаушкина

2023

Medicinskij sovet

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Erdosteine is a drug based on thiol and used at the beginning only as a mucolytic. The main indication for it is the treatment of acute and chronic lung diseases, accompanied by difficult sputum discharge. The therapeutic effect of erdosteine is due to the action of thiol metabolites, which, in addition to mucoactive, have antioxidant, anti-inflammatory and antibacterial activities. Experimental studies have shown that this drug reduces the degree of damage to lung tissue caused by oxidative stress, primarily by reducing the production of reactive oxygen species. It increases the concentration of IgA in the respiratory mucosa, thereby reducing the damaging effect of tobacco smoke on endothelial and macrophage cells. In the RESTORE clinical study, which studied the effect of erdosteine on the frequency of exacerbations of chronic obstructive pulmonary disease, it was demonstrated that it significantly reduces the risk, frequency and severity of COPD exacerbations, regardless of patients taking inhaled corticosteroids and eosinophil levels. Recent experimental studies have shown that erdosteine also has the ability to slow the progression rate of fibrosis in pulmonary tissue. It has been shown to inhibit the development of bleomycin-induced fibrosis. The authors of the study suggested that this effect may be related to the suppression of neutrophil migration metabolite erastheine, the inhibition of lipid peroxidation and, in general, the regulation of antioxidant protection mechanisms Data obtained in recent studies also open up new possibilities for the use of erdosteine in patients with bronchial asthma and idiopathic pulmonary fibrosis, significantly expanding the indications for its use.

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Protective role of erdosteine pretreatment on oleic acid–induced acute lung injury

Cited by 12 publications

References 28 publications

Effects of tocilizumab and dexamethasone on the downregulation of proinflammatory cytokines and upregulation of antioxidants in the lungs in oleic acid-induced ARDS

Effects of tocilizumab and dexamethasone on the downregulation of proinflammatory cytokines and upregulation of antioxidants in the lungs in oleic acid-induced ARDS

Therapeutic effects of minocycline on oleic acid-induced acute respiratory distress syndrome (ARDS) in rats

Clinical aspects of the use of erdosteine in respiratory diseases

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