The Effects of Dexamethasone and L-NAME on Acute Lung Injury in Rats with Lung Contusion

Kozan A., Kılıç N., Alacam H., Guzel A., Güvenç T., Acikgoz M.

INFLAMMATION, vol.39, no.5, pp.1747-1756, 2016 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 39 Issue: 5
  • Publication Date: 2016
  • Doi Number: 10.1007/s10753-016-0409-0
  • Journal Name: INFLAMMATION
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1747-1756
  • Keywords: CC-16, dexamethasone, iNOS, L-NAME, lung contusion, YKL-40, NECROSIS-FACTOR-ALPHA, CLARA CELL PROTEIN, NITRIC-OXIDE INHIBITION, CHITINASE-LIKE PROTEINS, PULMONARY CONTUSION, SECRETORY PROTEIN, EXPRESSION, INFLAMMATION, YKL-40, MACROPHAGES
  • Ondokuz Mayıs University Affiliated: Yes

Abstract

The therapeutic efficiency of an anti-inflammatory agent, dexamethasone (DXM), and a nitric oxide synthase (NOS) inhibitor, Nitro-L-arginine methyl ester (L-NAME), in lung tissue injury after lung contusion was investigated. Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), YKL-40, an inflammatory peptide, inducible NOS (iNOS), and Clara cell protein 16 (CC-16) were evaluated. Immunohistochemical analyses were also performed, and the lung tissue was examined histopathologically. The study consisted of eight groups of Sprague-Dawley rats (n = 10 in each group), weighing 250-300 g: (1) control, (2) contusion, (3) control + DXM, (4) contusion + DXM, (5) control + L-NAME (6) contusion + L-NAME, (7) control + DXM + L-NAME, and (8) contusion + DXM + L-NAME. A previously developed lung contusion model was used, in addition to the control group. The rats were administered DXM and L-NAME intraperitoneally (i.p.) at doses of 15 and 60 mg/kg/day, respectively. DXM and L-NAME administration decreased the iNOS level in the contusion groups. DXM increased the levels of YKL-40 and IL-10 in both the control and contusion groups, with higher levels in the contusion groups. L-NAME increased the serum level of IL-10 in the lung contusion groups. DXM increased the synthesis of CC-16 in the control and contusion groups. The combined use of a high-dose steroid and NOS inhibitor resulted in the death of the rats. Steroids can increase the level of cytokines, such as YKL-40 and IL-10, and the synthesis of CC-16 and prevent pneumonia, ALI/ARDS, and sepsis in lung contusion.