Amiodarone-Induced Pulmonary Toxicity in Fischer Rats: Release of Tumor Necrosis Factor Alpha and Transforming Growth Factor Beta by Pulmonary Alveolar Macrophages

Reinhart, Paul G.; Gairola, C. Gary

doi:10.1080/009841097159638

Cited by 3 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Certainly, one or more mechanisms involve direct cytologic injury by amiodarone, and these mechanisms might depend on a high focal concentration of amiodarone, with the accompanying high CT number. But, an important component of lung toxicity is immune based, involving both cellular elements, such as mast cells and lymphocytes, and cytokines such as tumor necrosis factor-a and transforming growth factor-b, 5 and these mechanisms could function independently of drug concentration. Thus, the possibility of false-negative CT scans is known, has a rational basis, and may be common.…”

Section: Editorial Commentmentioning

confidence: 99%

Amiodarone Pulmonary Toxicity and Professor Hounsfield

Mason¹

2001

Cardiovasc electrophysiol

View full text Add to dashboard Cite

Section: Editorial Commentmentioning

confidence: 99%

Amiodarone Pulmonary Toxicity and Professor Hounsfield

Mason¹

2001

Cardiovasc electrophysiol

View full text Add to dashboard Cite

“…AD is not permanent, however. A study (Reinhart and Gairola, 1997) in which rats were subjected to a single i.t. dose of AD (6.25 mg/kg) or water and then lavaged at 1, 3, or 6 weeks afterwards revealed that cultured BAL cells from AD-treated rats produced significantly more TNF-α than cells from control rats at the 3-and 6-week time points, but not at the 1 week time-point.…”

Section: Discussionmentioning

confidence: 99%

“…However, since the role of phospholipidosis in the development of AIPT is in question, and inflammation and fibrosis are the more damaging and life-threatening aspects of the toxicity, the i.t. route of administration is currently favored in animals studies of AIPT (Reinhart et al, 1996;Reinhart and Gairola, 1997;Card et al, 1999).…”

Section: Tnf-α Is Important In Various Ways Including Induction Of Imentioning

confidence: 99%

“…(Lindenschmidt et al, 1986). Intratracheal Models of AIPT have been developed in hamsters (Cantor et al, 1984;Daniels et al, 1989;Wang et al, 1992;Rafeiro et al, 1994;Leeder et al, 1994;Blake and Reasor, 1995a) and rats (Reinhart et al, 1996;Reinhart and Gairola, 1997) in an attempt to elucidate the mechanisms by which this disorder develops. Intratracheal instillation of AD leads to an inflammatory reaction in hamsters (Blake and Reasor, 1995a) and a fibrotic reaction in hamsters (Cantor et al, 1984;Blake and Reasor, 1995b) and rats (Reinhart et al, 1996).…”

Section: Tnf-α Is Important In Various Ways Including Induction Of Imentioning

confidence: 99%

See 1 more Smart Citation

Amiodarone-induced pulmonary toxicity in F344 rats

Taylor¹

View full text Add to dashboard Cite

Amiodarone-Induced Pulmonary Toxicity in F344 Rats. Michael D. TaylorAmiodarone (AD) is gaining support as a first-line antiarrhythmic drug despite its potentially fatal pulmonary toxicity involving inflammation and fibrosis. The goals of this study were to develop and characterize a rat model of amiodarone-induced pulmonary toxicity (AIPT). A protocol was developed in which male F344 rats were instilled intratracheally (i.t.) with AD (6.25 mg/kg with a 3.125 mg/ml solution) in sterile water or the sterile water vehicle on days 0 and 2, a protocol that led to the development of pulmonary fibrosis on day 28 in the AD-treated animals. Bronchoalveolar lavage (BAL) resulted in the increased recovery of alveolar macrophages, neutrophils, and eosinophils from i.t. AD-treated rats. The BAL cells recovered from AD-treated rats at day 3 produced more integrated phorbol-myristate-acetate stimulated luminol-dependent chemiluminescence over 20 minutes than BAL cells from control rats. These findings indicate that this model exhibits a transient pulmonary inflammation, with the potential for elevated oxidant production in the lungs, and subsequent pulmonary fibrosis. Also, serum levels of surfactant protein-D, a protein normally found in the lungs, was elevated in the serum of i.t. AD-treated rats, and is proposed as a biomarker for the toxicity. However, attempts to elucidate the cytokine signaling behind the inflammatory events were unsuccessful. It was discovered that AD instillation produces a rapid and massive damage to the alveolar-capillary barrier, and cellular death or damage to lung airway and parenchymal cells. This pathology is not consistent with that found in human AIPT. AD in solution was found to be at least partly in the form of a free radical, and capable of generating hydroxyl radicals. An attempt to modulate the toxicity of i.t. AD by incorporating water-soluble antioxidants in the drug solution was unsuccessful, and might have exacerbated the condition. No consistent evidence for deiodination of AD in solution was found, leaving the mechanism and significance of free radical generation by AD undetermined.iii

show abstract

A Single Instillation of Amorphous Silica Nanoparticles Induced Inflammatory Responses and Tissue Damage until Day 28 after Exposure

Park

Roh

Kim

et al. 2011

JOURNAL OF HEALTH SCIENCE

View full text Add to dashboard Cite

Synthetic amorphous silica nanoparticles (SiNPs) are seeing increased and widespread application in diagnosis, imaging, and drug delivery. In the present study, the inflammatory responses and histopathological changes caused by inflowing of SiNPs into the lung were studied in mice after a single intratracheal instillation. Changes in gene expression were also investigated in lung tissue using microarray analysis. As results, weight gain was significantly decreased in SiNP-treated mice on day 1 and 7 after instillation. The secretion of pro-inflammatory cytokines [interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α] and transforming growth factor (TGF)-β were also increased, and the distribution of cytotoxic T cells, natural killer (NK) cells, and natural killer T (NKT) cells with G1 arrest were increased. Microgranulomatous changes were observed on day 7 and 14. Furthermore, the gene expression was significantly affected on day 7. A total of 331 genes were up-regulated more than 2 fold, and 128 genes were down-regulated more than 2 fold. The secretion of inflammatory related cytokines, histopathological abnormalities, and the severity of gene expression changes decreased in a time-dependent manner. Based on these results, we suggest that SiNPs induce subchronic inflammatory responses and tissue damage in mice after a single intratracheal instillation.

show abstract

Amiodarone-Induced Pulmonary Toxicity in Fischer Rats: Release of Tumor Necrosis Factor Alpha and Transforming Growth Factor Beta by Pulmonary Alveolar Macrophages

Cited by 3 publications

References 0 publications

Amiodarone Pulmonary Toxicity and Professor Hounsfield

Amiodarone Pulmonary Toxicity and Professor Hounsfield

Amiodarone-induced pulmonary toxicity in F344 rats

A Single Instillation of Amorphous Silica Nanoparticles Induced Inflammatory Responses and Tissue Damage until Day 28 after Exposure

Contact Info

Product

Resources

About