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new anti-rheumatic drug leflunomide [Avara] and the associated risk of pulmonary toxicity: a histological study on the alveoli of albino rats
Bulletin of Alexandria Faculty of Medicine. 2007; 43 (4): 787-797
in English | IMEMR | ID: emr-82022
Responsible library: EMRO
ABSTRACT
Leflunomide [Avara] is a novel drug for the treatment of active rheumatoid arthritis. The controversy about the associated risk of respiratory infection in patients treated with leflunomide was the main drive for the present study. The present study aimed to demonstrate the histological changes that might occur in the alveolar structure of the lung in rats treated with leflunomide for 4 weeks and to investigate the effect of stoppage of drug administration for another 2 weeks. The present work was conducted on 30 adult male albino rats which were divided into 3 equal groups; group I [control group], group II [leflunomide treated group] which received leflunomide in an oral dose of 10mg/kg for 4 weeks. Group III [withdrawal group] the rats received the leflunomide treatment in a similar way to group II, then they were kept without treatment for another 2 weeks to test for possible spontaneous recovery. By the end of the experimental period, the animals were sacrificed and specimens from the lungs were taken, processed and examined by light and transmission electron microscopes. Examination of leflunomide treated group revealed marked alteration in the histological structure, as many alveoli appeared collapsed with evident thickening of the inter-alveolar septa which showed cellular infiltration and congested blood capillaries. Some red blood cells were seen extravasated in the alveolar spaces. Hyperplasia ofpneumocyte type II which appeared with empty lamellar bodies and pyknotic nuclei were depicted. Stoppage of drug administration for 2 weeks after treatment, did not succeed in restoration of the normal histological structure of the alveoli. On the contrary, severe cellular infiltration of the inter-alveolar septa were observed in the withdrawal group. The alveolar air spaces were seen obliterated surrounded with many pneumocytes type II which showed morphological changes including enlarged cells with swollen mitochondria. Plasma cells, lymphocytes, eosinophils, many degenerated ill-defined cells, multiple fibroblasts and excess collagen were seen. Trichrome stain also revealed excess collagen deposition in both leflunomide treated group and in the withdrawal group. The present results revealed that leflunomide induced lung toxicity with evident histological changes in the alveoli which mimicked that of interstitial pneumonitis. On the other hand, discontinuation of the drug for another 2 weeks did not succeed in spontaneous recovery or amelioration of these changes, most probably through its pharmacokinetics as regards the long half life of elimination of the drug and the increased risk of opportunistic infection
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Index: IMEMR (Eastern Mediterranean) Main subject: Arthritis, Rheumatoid / Pulmonary Alveoli / Rats / Microscopy, Electron / Histology / Lung Limits: Animals Language: English Journal: Bull. Alex. Fac. Med. Year: 2007

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Index: IMEMR (Eastern Mediterranean) Main subject: Arthritis, Rheumatoid / Pulmonary Alveoli / Rats / Microscopy, Electron / Histology / Lung Limits: Animals Language: English Journal: Bull. Alex. Fac. Med. Year: 2007