Amiodarone-induced Lung Injury Research Articles

Adipose Tissue-Derived Mesenchymal Stem Cells Protect Against Amiodarone-Induced Lung Injury in Rats.

Pulmonary fibrosis (PF) is a progressive and irreversible lung disease, characterized by poor prognosis with limited treatment options. Mesenchymal stem cells (MSCs) are multi-potent cells having the ability to self-renew and differentiate into multiple tissues, thus considered a novel treatment option. The present study aimed to investigate the possible antifibrotic effect of undifferentiated adipose tissue-derived mesenchymal stem cell (AD-MSC) therapy on PF experimentally induced in rats using amiodarone (AMD). AMD (30mg/kg) was given orally, once daily for 12 consecutive weeks to induce lung fibrosis. Following the confirmation of lung damage with histopathological examination, AD-MSCs (2 × 106 and 4 × 106 undifferentiated MSCs) were injected once intravenously, followed by 2months for treatment. AMD induced focal fibroblastic cells proliferation in the peribronchiolar tissue, as well as in between the collapsed emphysematous alveoli. Also, AMD significantly increased serum and lung homogenate fibroblast growth factor-7 (FGF7), Clara cell protein-16 (CC16), and cytokeratin -19 (CK19) levels, as well as the expression of both iNOS and NFкB in the lung alveoli. Moreover, AMD caused excessive collagen deposition and increased alpha smooth muscle actin (α-SMA) expression. All findings significantly regressed on stem cell therapy in both doses, with superior effect of the high dose, providing evidence that adipose tissue-derived MSCs could be a promising approach for the treatment of PF. Graphical Abstract.

The possible therapeutic role of mesenchymal stem cells in amiodarone-induced lung injury in adult male albino rats

Background and aim Lung injury and even pulmonary fibrosis represent a known adverse effect of amiodarone. No effective treatment was reported for pulmonary fibrosis except lung transplantation. Stem cell therapy holds a great promise for the repair of injured tissues. Mesenchymal stem cells (MSCs) have the potential to present a new trend of treatment. This work aimed to study the effect of bone marrow-MSCs on amiodarone-induced lung injury in albino rats by histological methods. Materials and methods Forty-two adult male albino rats were used. Seven rats were used as a source of bone marrow-MSCs. Thirty-five rats were divided into the following groups: negative control group included seven rats that received no treatment; vehicle control group included seven rats that received polysorbate 80; amiodarone group included 14 rats that received daily oral amiodarone for 6 weeks and were subdivided into two equal subgroups as subgroup 3a (amiodarone administrated) and subgroup 3b (kept for 4 weeks after amiodarone stoppage); and stem cell-treated group included seven rats that received stem cells after amiodarone stoppage. Lung specimens were examined histologically. Results Amiodarone group showed disrupted lung architecture, collapsed alveoli, and significant increase in the thickness of interalveolar septa. Bronchioles showed thickened smooth muscle layer and obliterated lumens. Highly significant increase in area percent of collagen fibers was observed. In stem cell group, there was improvement of these histological changes. Conclusion MSCs can improve the deleterious effects associated with amiodarone-induced lung injury.

Therapeutic Effect of Adipose Derived Stem Cells versus Atorvastatin on Amiodarone Induced Lung Injury in Male Rat.

Background and ObjectivesAmiodarone (AM), a class 3 antiarrhythmic drug, has been associated with variety of adverse effects, the most serious of which is pulmonary toxicity. Ator (A) is a statin, known for their immunomodulatory and anti-inflammatory activities. Recent studies provide evidence of potential therapeutic effect of statins on lung injury. Adipose derived stem cells (ADSCs) have shown great promise in the repair of various tissues. The present study aimed at investigating and comparing the possible therapeutic effect of A and ADSCs on AM induced lung injury in albino rats.Methods and Results34 adult male albino rats were divided into 5 groups: control group (Gp I), A group (Gp II) received 10 mg/kg of A orally 6 days (d)/week (w) for 4 weeks (ws), AM group (Gp III) received 30 mg/kg of AM orally 6 d/w for 4 ws, AM&A group (Gp IV) received AM for 4ws then A for other 4 ws and AM&SCs group (Gp V) received AM for 4 ws then injected with 0.5 ml ADSCs on 2 successive days intravenously (IV). Histological, histochemical, immunohistochemical and morphometric studies were performed. Group III displayed bronchiolitis obliterans, thickened interalveolar septa (IAS) and thickened vascular wall which were proven morphometrically. Increased area% of collagen fibers and apoptotic changes were recorded. All findings regressed on A administration and ADSCs therapy.ConclusionAtor proved a definite ameliorating effect on the degenerative, inflammatory, apoptotic and fibrotic changes induced by AM. ADSCs administration denoted more remarkable therapeutic effect compared to A.

Effect of green tea on amiodarone-induced lung injury in albino rats

Introduction Amiodarone (AM) is an antiarrhythmic agent used in the treatment and prophylaxis of postoperative atrial fibrillation. It has some serious side effects, including pulmonary toxicity. Green tea is among the most popular beverages. It is characterized by the presence of catechins, a subgroup of polyphenols, known as a powerful antioxidant. Aim The aim of the study was to determine the toxic effects of AM as an animal model on lung injury and evaluate the possible role of green tea extract against these effects in albino rats. Materials and methods The study included 21 adult male albino rats weighing 180–200 g. They were divided into three equal groups, comprising seven rats each. Group I was considered the control group. Group II rats were given AM orally at 30 mg/kg daily for 2 weeks. Group III rats were given green tea extract orally at 150 mg/kg daily for 2 weeks concomitantly with AM as in group II. The lungs were dissected out and processed for histological and immunohistochemical study. Morphometric and statistical studies were also carried out. Results Administration of AM in group II resulted in obvious distortion to the lung architecture. Collapsed alveoli, vacuolar degeneration of pneumocytes type II, thickening of interalveolar septa, and significant increase in collagen deposition were observed. Significantly increased number of macrophages was observed in group II. However coadministration of green tea extract with AM in group III showed obvious preservation of the lung architecture. Conclusion Administration of AM in rats induced severe lung damage, whereas concomitant administration of green tea extract effectively ameliorated lung tissue damage.

Comparative Study between Intravenous and Intraperitoneal Stem Cell Therapy in Amiodarone Induced Lung Injury in Rat.

Background and Objectives:The fibrosing form of lung injury (occupational, environmental, infective or drug induced) is associated with significant morbidity and mortality. Amiodarone (AM), often prescribed for control of arrhythmias is considered a potential cause. No effective treatment was confirmed, except lung transplantation. Intravenous (IV) stem cell therapy may produce pulmonary emboli or infarctions. Despite being commonly used in clinical practice, the intraperitoneal (IP.) route has been rarely used for cell delivery. The present study aimed at investigating and comparing the possible effect of IP stem cell therapy (SCT) on pulmonary toxicity versus the intravenous route in a rat model of amiodarone induced lung damage.Methods and Results:36 adult male albino rats were divided into 4 groups. Rats of AM group were given 30 mg/kg daily orally for 4 weeks. Rats of IV SCT group were injected with stem cells in the tail vein. Rats of IP SCT group received IP cell therapy. Histological, histochemical, immunohistochemical and morphometric studies were performed. Obstructed bronchioles, overdistended alveoli, reduced type I pneumocytes, increased thickness of alveolar septa and vessels wall besides increased area% of collagen fibers regressed in response to IV and IP SCT. The improvement was more obvious in IV group. The area% of Prussion blue +ve and CD105 +ve cells was significantly higher in IV group.Conclusions:Cord blood MSC therapy proved definite amelioration of lung injury ending in fibrosis. The effect of IP SCT was slightly inferior to that of IV SCT, which may be overwhelmed by repeated IP injection.

Amiodarone-induced pulmonary toxicity: an under-recognized and severe adverse effect?

Several forms of pulmonary disease occur among patients treated with amiodarone, i.e. chronic interstitial pneumonitis, organizing pneumonia, ARDS, a solitary pulmonary mass of fibrosis. The prevalence is estimated to be about 5%. Two major hypotheses of amiodarone-induced pulmonary injury include direct cytotoxicity and a hypersensitivity reaction. Given the frequency and potential severity of amiodarone-induced pulmonary toxicity, early detection is desirable. Unfortunately, there are no adequate predictors of pulmonary toxicity due to amiodarone. Patients who should benefit from amiodarone should be carefully selected and the lowest effective dosage of amiodarone should be taken. Amiodarone-induced pulmonary toxicity is a diagnosis of exclusion. Pulmonary evaluation with chest X-ray and pulmonary function testing, including diffusion capacity for carbon monoxide is recommended when amiodarone is started. A documented decline in the diffusing capacity of greater than 20% is useful in suggesting the need for closer monitoring or for further diagnostic testing. Although the optimal frequency of follow-up has not been determined, most cases of amiodarone-induced lung injury develop during the first 2 years of treatment and disease onset usually is slow. Pulmonary function tests and imaging may be performed every 3-6 months, depending on the presumed individual risk. Treatment of amiodarone pulmonary toxicity consists primarily of stopping amiodarone. Corticosteroid therapy can be life-saving for severe cases and for patients with less severe disease in whom withdrawal of amiodarone is not desirable. Due to its accumulation in fatty tissues and long elimination half-life, pulmonary toxicity may initially progress despite drug discontinuation and may recur after steroid withdrawal. The prognosis of amiodarone lung disease is generally favourable.

Clinicopathologic manifestation of amiodarone-induced lung injury

To study the clinical, pathologic and radiologic features of amiodarone-induced lung injury. The clinical, pathologic and radiologic features, including treatment and follow-up information of three cases diagnosed as amiodarone-induced lung injury from October 2004 to October 2005 in the Peking Union Medical College Hospital were reviewed. All the patients were males, with age ranging from 35 to 64 years. The duration of symptoms varied from 20 days to 3 years. All presented with cough. Worsening dyspnea and inspiratory crackles were noted in two patients. Computerized tomography showed bilateral patchy infiltration, ground-glass appearance and accentuation of bronchovascular markings. The most common pathologic manifestations included cellular interstitial pneumonia associated with intra-alveolar collections of macrophages and type II pneumocyte hyperplasia. Some of the macrophages contained finely vacuolated cytoplasm. An organizing pneumonia pattern was seen in one patient. Amiodarone-induced lung injury has characteristic pathologic features which may provide clues to diagnosis. Correlation with clinical and radiologic findings is also important.

Low dose amiodarone-induced lung injury

Amiodarone-induced lung injury is a potentially lethal side-effect of amiodarone. In an attempt to assesss its risk, we studied the incidence and clinical profile of Chinese patients prescribed with low dose amiodarone.

Amiodarone-induced pulmonary fibrosis in hamsters.

Amiodarone, a cardiac antiarrhythmic agent, has been associated with the development of interstitial pulmonary fibrosis in patients receiving prolonged therapy with the drug. To further assess the toxic effects of amiodarone on lung tissue, Syrian hamsters were given a single intratracheal insufflation of the agent and evaluated for histologic evidence of lung injury. Control animals received intratracheal insufflations of the vehicle in which amiodarone was dissolved. After an initial, transient alveolitis in both experimental and control animals, the amiodarone-treated lungs developed increased interstitial thickening due to fibrinous exudates, alveolar epithelial hyperplasia, inflammatory cell infiltrates, and marked deposition of collagen manifested on trichrome staining. Controls, in contrast, showed nearly complete resolution of the initial alveolitis. An unusual feature of the amiodarone-induced lung injury was reemergence of the alveolitis between 5 and 14 days, which included a marked influx of eosinophils into the lung. Although the precise mechanism of the lung injury is not known, the persistence of the acute inflammatory cells as well as the presence of eosinophils suggests a hypersensitivity-type reaction. Furthermore, the progression of lung injury to fibrosis after a single insult with the drug suggests that mere discontinuation of amiodarone therapy in humans may not reverse the disease process, but that corticosteroid therapy may also be required. Amiodarone appears to be a useful agent to induce diffuse fibrotic reactions in the lung that morphologically resemble idiopathic pulmonary fibrosis in humans.