Effect of lutein on methotrexate-induced oxidative lung damage in rats: a biochemical and histopathological assessment

Abstract

Background/aims: This study aimed to investigate the effect of lutein on methotrexate (MTX)-induced pulmonary toxicity in rats biochemically and histopathologically.

Methods: The rats in the MTX + lutein (MTXL, n = 6) group were given 1 mg/kg of lutein orally. A 0.9% NaCl solution was administered orally to the MTX (n = 6) group and the healthy group (HG, n = 6). One hour later, a single 20 mg/kg dose of MTX was injected intraperitoneally in the MTXL and MTX. Lutein or 0.9% NaCl solution was administered once a day for 5 days. At the end of this period, malondialdehyde (MDA), myeloperoxidase (MPO), total glutathione (tGSH), interleukin 1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) were measured in the lung tissues from the animals euthanized with 50 mg/kg thiopental sodium anesthesia. Subsequently, histopathological examinations were performed.

Results: The levels of MDA, MPO, IL-1β, and TNF-α in the lung tissue of the MTX were significantly higher than those of the MTXL and HG groups (p < 0.0001), and the amount of tGSH was lower. The histopathological findings in the MTX group, in which the oxidants and cytokines were higher, were more severe.

Conclusion: Lutein prevented the MTX-induced oxidative lung damage biochemically and histopathologically. This result indicates that lutein may be useful in the treatment of MTX-induced lung damage.

Keywords: Lung; Lutein; Methotrexate; Rats.

Figure 1.

Effects of methotrexate (MTX) and lutein on the levels of (A) malondialdehyde (MDA), (B) myeloperoxidase (MPO), and (C) total glutathione (tGSH) in the lung tissue of rat groups. MTXL, MTX + lutein. ^ap < 0.0001 according to the healthy group (HG) group, ^bp < 0.0001 according to the MTX group.

Figure 2.

Effects of methotrexate (MTX) and lutein on the levels of (A) interleukin 1 beta (IL-1β) and (B) tumor necrosis factor alpha (TNF-α) in the lung tissue of rat groups. MTXL, MTX + lutein. ^ap < 0.0001 according to the healthy group (HG) group, ^bp < 0.0001, according to the MTX group.

Figure 3.

(A) The normal visceral epithelium (straight arrow), alveolar (striped arrow), pulmonary artery (round arrow), and bronchial epithelium (square arrow) structures are observed in the lung tissue of the healthy group animal group (H&E, ×100). (B) The animal group treated with methotrexate shows significant polymorphonuclear neutrophil infiltration (straight arrow), severe hemorrhage (striated arrow), alveolar destruction (bilateral arrow), and edema in the lungs (H&E, ×100). (C) The vascular wall of lutein-treated lung tissue is seen as normal, except for slight thickening, dilatation, congestion (flat arrow), and mild alveolar edema (double sided arrow) (H&E, ×100).