Effect of the antirheumatic drug leflunomide (Avara) on the lungs of adult male albino rats and the possible protective effect of N-acetylcysteine: histological and immunohistochemical study

Abstract

Objective The present study was conducted to throw light on the histological effects of the antirheumatic drug leflunomide (Avara) on the lungs of adult male albino rats, and to clarify the possible protective effect of N-acetylcysteine. Background Leflunomide (Avara) is an immunomodulating agent and disease-modifying antirheumatic drug with anti-inflammatory and immunosuppressive activity. N-acetylcysteine belongs to a class of drugs called antioxidants which may reduce the amount of damage caused by inflammation or active damage of the lungs. Materials and methods A total of 60 adult male albino rats were used in the present study. They were divided into four groups. Group I: The control group composed of 20 rats. Group II: The N-acetylcysteine-treated group composed of 10 rats received N-acetylcysteine in a daily oral dose of 200 mg/kg body weight. Group III: The leflunomide-treated group composed of 20 rats receiving leflunomide on a daily oral dose of 10 mg/kg body weight. Then, half the animals were killed 4 weeks after the treatment (subgroup IIIa), and the other half were left without treatment for another 2 weeks and served as the recovery group (subgroup IIIb). Group IV: The protected group composed of 10 rats receiving combined treatment of both leflunomide and N-acetylcysteine in the same previous doses and route of administration for 4 weeks. At the end of the study, animals were killed and specimens from the lungs were processed for both L/M, E/M, and immunohistochemical study (using caspase-3 immunostaining). Morphometric study for the number of pneumocyte type II was counted, and the thicknesses of the interalveolar septa were done and statically analyzed. Results The results of this study revealed that leflunomide treatment caused considerable histological, immunohistochemical, and ultrastructural changes in the lungs. Concomitant administration of N-acetylcysteine with leflunomide resulted in remarkable improvement, whereas arrest of treatment for 2 weeks revealed mild improvement. Conclusion N -acetylcysteine is proven to have a protective effect on the lungs against hazardous effects induced by leflunomide treatment. Therefore, strict follow-up and coadministration of N-acetylcysteine are highly recommended for those patients who use leflunomide.