Literature analysis of lung toxicity related to cyclin-dependent kinase 4/6 inhibitors / 中国药房

OBJECTIVE To provide reference for rational use of cyclin-dependent kinase 4/6 （CDK4/6） inhibitors. METHODS Retrieved from Web of Science， PubMed， SpringerLink， CNKI， Wanfang Data and VIP database， and so on， the literature about lung toxicity related to CDK4/6 inhibitors were collected and analyzed statistically with Excel 2013 software. RESULTS A total of 12 literature which met the inclusion and exclusion criteria were included； 13 patients were involved， among which 3 cases were from the United States， 3 from Japan， 2 from India， and 1 from Israel， Spain， France， Australia and Saudi Arabia respectively； all patients were female， aged between 43-89 years， of whom 8 were treated with palbocicilib， 3 with abemacilib， and 2 with ribociclib. The lung toxicity of patients after medication occurred from 1 week to 15 months； the majority of patients were hospitalized with the symptom such as difficulty breathing， chest tightness， shortness of breath， dry cough， etc. The lung toxicity mainly manifested as interstitial lung disease， eosinophilic pneumonia， mediastinal and pulmonary granulomatous reaction， drug-induced pneumonia， diffuse alveolar damage， organizing pneumonia and so on. The shortest treatment duration was 3 weeks， and the longest was 6 months. The treatment measures included drug withdrawal， intravenous use of antibiotics， intravenous use of systemic steroids， oxygen inhalation， and so on； after treatment， 8 patients improved or recovered， and 5 patients died due to deterioration. One patient developed lung toxicity again after reuse of such drugs and must stop drugs permanently. CONCLUSIONS Lung toxicity related to CDK4/6 inhibitors possibly cause mortality. It is necessary to make early judgment， stop the drug in time， and give patients systemic steroids， oxygen inhalation and other treatment measures as soon as possible.

Pulmonoprotective Action of Zataria multiflora Ethanolic Extract on Cyclophosphamide-Induced Oxidative Lung Toxicity in Mice / 中国结合医学杂志

OBJECTIVE@#To evaluate the protective effect of Zataria multiflora extract, an antioxidative medicinal plant, against cyclophosphamide (CP)-induced oxidative lung damage in mice.@*METHODS@#Mice were intraperitoneally pre-treated with various doses of Zataria multiflora extract (50, 100, 200, and 400 mg/kg) once daily for 7 consecutive days. Animals were then injected with a single 200 mg/kg intraperitoneal dose of CP 1 h after the last administration of O. vulgare. Twenty-four hours later, mice were euthanized, the lungs were immediately removed, and biochemical and histological studies were conducted.@*RESULTS@#A single dose of CP markedly altered the levels of several biomarkers associated with oxidative stress in lung homogenates. Pretreatment with Zataria multiflora significantly inhibited the elevation of lipid peroxidation level and the depletion in glutathione content, and superoxide dismutase and catalase activities induced by CP in lung. In addition, Zataria multiflora effectively alleviated CP-induced histopathological abnormality and pulmonary damages in mice lung tissues.@*CONCLUSIONS@#The results reveal that Zataria multiflora protects lung tissues from CP-induced toxicity and suggest a role for oxidative stress in the pathogenesis of lung toxicity produced by CP in mice. Because Zataria multiflora has been extensively used as an additive agent and is regarded as safe, it may be used concomitantly as a good supplement for reducing organ toxicity in patients undergoing chemotherapy, besides their consolidated ethnopharmacological uses.

Vitamin E and Sodium Selenite Against Mercuric Chloride-Induced Lung Toxicity in the Rats

The aim of the present study was to elucidate the possible protective role of vitamin E and / or sodium selenite on mercuric chloride-induced oxidative stress and histopathological changes in the lung tissue of the rats. Adult male albino Wistar rats were exposed to mercuric chloride (1.0 mg/kg day) for four weeks. Treatment with mercuric chloride led to oxidative stress by enhancing MDA level and also decreasing superoxide dismutase (SOD), catalase (CAT) glutathione peroxidase (GPx) and glutathione S transferaz (GST) activities. However, mercuric chloride exposure resulted in histopathological changes in the lung tissue in the rats. MDA level and SOD, CAT GPx and GST activities and histopathological changes modulated in concomitantly supplementation of vitamin E (100 mg/kg day) and /or sodium selenite (0.25 mg/kg day) to mercuric chloride-treated groups.

Amiodarone-Induced Pulmonary Toxicity: Percutaneous Needle Aspiration Biopsy and Ultrastructural Findings / 이화의대지

Amiodarone has been widely used for supraventricular and ventricular arrhythmias and many patients benefit from its effectiveness in treating potentially life-threatening arrhythmias. However, this drug can cause multi-organ toxicity, including amiodarone-induced pulmonary toxicity (APT). Not only does amiodarone have a long half-life but also is lipophilic and therefore can easily accumulate in tissues. Hence, it is difficult to monitor therapeutic levels and side effects, making it difficult to predict toxicities. In this case, we describe multi-organ complications secondary to amiodarone use, especially APT combined with pneumonia with atypical pathogens and pulmonary hemorrhage. The patient reached a high cumulative dose of amiodarone despite a low maintenance dose of amiodarone. This case highlights an unusual presentation of APT with multi-organ toxicity and we review articles regarding the association between the cumulative dose of amiodarone and amiodarone-induced toxicities.

Prediction of radiation-induced lung toxicity in locally advanced non-small cell lung cancer treated with chemoradiotherapy by functional lung dose-volume histogram / 中华放射医学与防护杂志

Objective To investigate the correlation between functional lung dose-volume histogram (f-DVH) parameters and radiation-induced lung toxicity (RILT) in patients of locally advanced non-small cell lung cancer (NSCLC) treated with late-course accelerated hyperfractionated radiotherapy and chemotherapy,and to identify the excellent predictors of f-DVH and their reference thresholds.Methods A total of 51 patients of NSCLC at stage Ⅲ underwent PET/CT/SPECT coregistered image guided radiotherapy.Philips Pinnacle3 planning system was used for delineation of the target volume and organs at risk so as to establish the three dimensional conformal radiotherapy or intensity-modulated radiotherapy treatment plans.The version 3.0 of the NCI Common Terminology Criteria for Adverse Events was used to evaluate the grade of RILT,and analyze the correlation of the DVH parameters of the total lung (TL),ipsilateral lung (IL),and functional lung (FL) and RILT,and to identify the excellent predictors.The median follow-up was 15 months.Results During the follow-up,10 cases of RILT (19.6%) ≥grade 2 were observed.Single factor analysis showed that the V5-V40 of TL,V5-V/20 of IL,and V5-V50 of FL were all related to the occurrence of RILT,and multiple factor analysis showed that TL-V15 and FL-V20remained associated with RILT (P = 0.005 and P = 0.016).According to ROC analysis,the V10 (45.38%) of FL was the most sensitive predictor with a sensitivity rate of 90.0% and 1/25 (27.78%) of FL was the most specific predictor with a specificity rate of 90.24%.The sensitivity,specificity and accuracy of V20 of FL were 70.00%,73.17%,and 74.90%,respectively.Conclusions The occurrence of RILT is closely associated with multiple f-DVH parameters of FL,and f-DVH has good sensitivity and specificity for prediction.

Effects of Aminotriazole on Lung Toxicity of Paraquat Intoxicated Mice / 결핵

BACKGROUND: Paraquat, a widely used herbicide, is extremely toxic, causing multiple organ failure in humans. Paraquat especially leads to irreversible progressive pulmonary fibrosis, which is related to oxygen free radicals. However, its biochemical mechanism is not clear. Natural mechanisms that prevent damage from oxygen free radicals include changes in glutathione level, G6PDH, superoxide dismutase(SOD), catalase, and glutathione peroxidase. The authors think catalase is closely related to paraquat toxicity in the lungs METHOD: The effects of 3-amino-1,2,4-triazole(aminotriazole), a catalase inhibitor, on mice administered with paraquat were investigated. We studied the effects of aminotriazole on the survival of mice administered with paraquat, by comparing life spans between the group to which paraquat had been administered and the group to which a combination of paraquat and aminotriazole had been administered. We measured glutathion level, glucose 6-phosphate dehydrogenase(G6PDH), superoxide dismutase(SOD), catalase, and glutathione peroxidase(GPx) in the lung tissue of 4 groups of mice: the control grouts, group A(aminouiazole injected), group B(paraquat administered), group C(Paraquat and aminotriazole administered). RESULTS: The mortality of mice administered with paraquat which were treated with aminotriazole was significantly increased compared with those of mice not treated with aminotriazole. Glutathione level in group B was decreased by 20%, a significant decrease compared with the control group. However, this level was not changed by the administration of aminotriazole(group C). The activity of G6PDH in all groups was not significantly changed compared with the control group. The activities of SOD, catalase, and glutathione peroxidase(GPx) in the lung tissue were significantly decreased by paraquat administration(group B); catalase showed the largest decrease. Catalase and GPX were significantly decreased by aminotriazole treatment in mice administered with paraquat but change in SOD activity was not significant.(group C). CONCLUSION: Decrease in catalase activity by paraquat suggests that paraquat toxicity in the lungs is closely related to catalase activity. Paraquat toxicity in mice is enhanced by aminotriazole administration, and its result is related to the decrease of catalase activity rather than glutathione level in the lungs. Production of hydroxyl radicals, the most reactive oxygen metabolite, is accelerated due to increased hydrogen peroxide by catalase inhibition and the lung damage probably results from nonspecific tissue injury of hydroxyl radicals.