Histopathological Study of Cyclosporine Pulmonary Toxicity in Rats

Abstract

Cyclosporine is considered one of the common worldwide immunosuppressive drugs that are used for allograft rejection prevention. However, articles that address adverse effects of cyclosporine use on the vital organs such as lung are still few. This study aims to investigate pulmonary toxic effect of cyclosporine in rats by assessment of pulmonary histopathological changes using light and electron microscope examination. Sixty male adult albino rats were divided into three groups; each group consists of twenty rats. The first received physiological saline while the second and third groups received 25 and 40 mg/kg/day of cyclosporine, respectively, by gastric gavage for forty-five days. Cyclosporine reduced the lung and body weight with shrinkage or pyknotic nucleus of pneumocyte type II, degeneration of alveoli and interalveolar septum beside microvilli on the alveolar surface, emphysema, inflammatory cellular infiltration, pulmonary blood vessels congestion, and increase of fibrous tissues in the interstitial tissues and around alveoli with negative Periodic Acid-Schiff staining. Prolonged use of cyclosporine induced pulmonary ultrastructural and histopathological changes with the lung and body weight reduction depending on its dose.

Figure 1

The effect of cyclosporine different doses on the rats' lung weight.

Figure 2

(a) A photomicrograph of transverse section in the control rat lung shows normal architecture of alveoli (A) with thin interalveolar septa (s) and normal interstitial tissues (I) (H&E ×400). (b) A photomicrograph of transverse section in the second group rat lung shows marked thickening of interstitial tissues (IS) with numerous areas of cellular infiltration (I), congested blood capillaries (bv), and bronchiole (B) with widening alveoli (A) (H&E ×400). (c) A photomicrograph of transverse section in the third group rat lung shows loss of normal architecture, cellular infiltration (I), fragmentation and degeneration of alveoli and interalveolar septum (s) with a subsequent compensatory dilatation of alveoli (A), thickened and congested pulmonary blood vessels (bv), and degenerated bronchiolar wall (B) (H&E ×400).

Figure 3

(a) A photomicrograph of transverse section in the control rat lung shows normal distribution of fibrous tissues and architecture of alveoli (A) with thin interalveolar septa (s) and normal interstitial tissues (I) (Mallory ×400). (b) A photomicrograph of transverse section in the second group rat lung shows mild distribution of fibrous tissues around alveoli (A) with thickening of the interalveolar septa (IS) and bronchiole (B) (Mallory ×400). (c) A photomicrograph of transverse section in the third group rat lung shows loss of normal architecture, increase of fibrous tissues around alveoli (A), subsequent compensatory dilatation of other alveoli, marked thinning of the interalveolar septum (s) with an increase of fibrous tissues in the areas of interstitial tissues (IS), and thickened and congested pulmonary blood vessels which contain hemorrhagic blood cells (bv) (Mallory ×400).

Figure 4

(a) A photomicrograph of transverse section in the control rat lung shows positive PAS staining with normal architecture of alveoli (A) with thin interalveolar septa (s) and normal interstitial tissues (I) (PAS ×400). (b) A photomicrograph of transverse section in the second group rat lung shows moderate positive PAS staining with nearly normal architecture of alveoli (A), thick interalveolar septa (s), and interstitial tissues (I) (PAS ×400). (c) A photomicrograph of transverse section of third group rat lung shows negative PAS staining, accumulation of inflammatory cells near the blood vessels with abnormal architecture of alveoli (A), and destruction of the interalveolar septa (s) and interstitial tissues (I) (PAS ×400).

Figure 5

(a) Electronic microscopic picture of the control rat lung shows rounded nucleus (N) of pneumocyte type II, lamellar bodies (L) around the nucleus, and mitochondria (m) in cytoplasm with microvilli (Mv) on the surface of alveoli (A) (×10000). (b) Electronicmicroscopic picture of the second group rat lung shows a shrinkage nucleus (N) of pneumocyte type II, vacuoles and congested blood capillaries (C) filled with the blood (b) in the cytoplasm and around the nucleus, degenerated mitochondria (m) in cytoplasm with degenerated microvilli (Mv) on the surface of alveoli (A) (×10000). (c) Electronic microscopic picture of the third group rat lung shows pyknotic nucleus (N) of pneumocyte type II, a variable number of vacuoles (v) and more congested blood capillaries (C) filled with the blood (b) around the nucleus, and degenerated mitochondria (m) in cytoplasm with degenerated microvilli (Mv) on the surface of alveoli (A) (×10000).