Expression of caspase 1 and histomorphology of lung after cladribine treatment.


Journal

Advances in clinical and experimental medicine : official organ Wroclaw Medical University
ISSN: 1899-5276
Titre abrégé: Adv Clin Exp Med
Pays: Poland
ID NLM: 101138582

Informations de publication

Date de publication:
Jan 2019
Historique:
pubmed: 7 8 2018
medline: 27 8 2019
entrez: 7 8 2018
Statut: ppublish

Résumé

Cladribine is a useful immunosuppressive drug for the treatment of autoimmune diseases, leukemias and multiple sclerosis (MS). Despite the drug having low toxicity, side effects have been reported connected with myelosuppression, neutropenia and severe anemia. The objective of this study was to investigate the influence of cladribine on lung pathomorphology and the expression of caspase 1 using immunohistochemistry method. The study was conducted on Wistar rats, which were divided into a control group (C) and an experimental group (E). In group C, the rats were given a 0.9% NaCl solution by a subcutaneous injection, at the same dose as the dose of drug used in the experiment. In group E, the animals received cladribine at a dose of 0.07 mg/kg/24 h by a subcutaneous injection. The animals were decapitated 24 h following the last dose. To detect collagen deposition, we utilized Masson's trichrome staining. To evaluate the intensity of the inflammatory process in the lung, an immunohistochemistry reaction was carried out with the use of caspase 1. In group E, we observed an increase in the thickness of space between the alveoli. A statistically significant (p < 0.017243) difference between the thicknesses of the interalveolar septum was seen between the research groups. In E group, we observed regions with collagen deposition, alveolar epithelial cell hyperplasia, hyperemia and inflammatory cell infiltration. Caspase 1 activity was higher in group E. The immunohistochemical reaction with caspase 1 was positive in 49% of all the interalveolar cells in group E; however, in group C about 13% of the interalveolar cell showed positive immunohistochemistry (IHC) response. Cladribine-based therapy might have negative influence on lung morphology. The interstitial changes in the lung tissue suggest that cladribine is a drug that may be the cause of drug-induced lung disease and may lead to several respiratory disorders.

Sections du résumé

BACKGROUND BACKGROUND
Cladribine is a useful immunosuppressive drug for the treatment of autoimmune diseases, leukemias and multiple sclerosis (MS). Despite the drug having low toxicity, side effects have been reported connected with myelosuppression, neutropenia and severe anemia.
OBJECTIVES OBJECTIVE
The objective of this study was to investigate the influence of cladribine on lung pathomorphology and the expression of caspase 1 using immunohistochemistry method.
MATERIAL AND METHODS METHODS
The study was conducted on Wistar rats, which were divided into a control group (C) and an experimental group (E). In group C, the rats were given a 0.9% NaCl solution by a subcutaneous injection, at the same dose as the dose of drug used in the experiment. In group E, the animals received cladribine at a dose of 0.07 mg/kg/24 h by a subcutaneous injection. The animals were decapitated 24 h following the last dose. To detect collagen deposition, we utilized Masson's trichrome staining. To evaluate the intensity of the inflammatory process in the lung, an immunohistochemistry reaction was carried out with the use of caspase 1.
RESULTS RESULTS
In group E, we observed an increase in the thickness of space between the alveoli. A statistically significant (p < 0.017243) difference between the thicknesses of the interalveolar septum was seen between the research groups. In E group, we observed regions with collagen deposition, alveolar epithelial cell hyperplasia, hyperemia and inflammatory cell infiltration. Caspase 1 activity was higher in group E. The immunohistochemical reaction with caspase 1 was positive in 49% of all the interalveolar cells in group E; however, in group C about 13% of the interalveolar cell showed positive immunohistochemistry (IHC) response.
CONCLUSIONS CONCLUSIONS
Cladribine-based therapy might have negative influence on lung morphology. The interstitial changes in the lung tissue suggest that cladribine is a drug that may be the cause of drug-induced lung disease and may lead to several respiratory disorders.

Identifiants

pubmed: 30079995
doi: 10.17219/acem/76253
doi:

Substances chimiques

Immunosuppressive Agents 0
Cladribine 47M74X9YT5
Caspase 1 EC 3.4.22.36

Types de publication

Journal Article

Langues

eng

Pagination

59-65

Auteurs

Marta Lis-Sochocka (M)

Department of Histology and Embryology with Experimental Cytology Unit, Medical University of Lublin, Poland.

Patrycja Chylińska-Wrzos (P)

Department of Histology and Embryology with Experimental Cytology Unit, Medical University of Lublin, Poland.

Ewelina Wawryk-Gawda (E)

Department of Histology and Embryology with Experimental Cytology Unit, Medical University of Lublin, Poland.

Barbara Jodłowska-Jędrych (B)

Department of Histology and Embryology with Experimental Cytology Unit, Medical University of Lublin, Poland.

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Classifications MeSH