Analysis of the protective biochemical and pathologic effects of aminoguanidine on an experimental aspiration pneumonitis model induced by bile acids

Abstract

Background: Gastroesophageal reflux (GER) is a common clinical pathology detected in childhood. Bile acids (BAs) are present in reflux and cause various pathologies in the esophagus, the larynx, and the lungs.

Objective: We aimed to show if aminoguanidine (AG) contributes to the biochemical and histopathologic treatment of experimental aspiration pneumonitis induced by BAs.

Methods: Twenty-eight female Sprague Dawley rats were used. There were 4 groups in the study: (1) group aspirated with 0.9% saline (n = 7), (2) group aspirated with 0.9% saline and treated with AG (n = 7), (3) group aspirated with a solution of 10 mg/kg taurocholic acid and 5 mg/kg taurochenodeoxycholate (n = 7), and (4) group aspirated with BA and treated with AG (n = 7). The saline and BA solutions were administered as 1 mL/kg intratracheally. The AG was administered intraperitoneally twice a day at a 150 mg/kg dose for 7 days. The different histopathologic and biochemical parameters were analyzed.

Results: Clara cell protein 16 and malondialdehyde levels were found to be significantly higher in the BA group than in the group where saline was administered; however, they were significantly lower in the BA + AG group than in the BA group. The total superoxide dismutase activity decreased significantly in the BA group compared with the group where saline was administered. A significant increase in superoxide dismutase activity was observed in the BA + AG group when compared with the group where only BA was administered. When the group where BA was administered solely was compared with the group where saline was administered, peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar histiocytes, interstitial fibrosis, and granuloma were significantly higher in the BA group than in the saline group. When the BA + AG group was compared with the BA group, peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar histiocytes, interstitial fibrosis, and granuloma were found to be significantly lower.

Conclusions: Oxidant stress increases and antioxidant capacity decreases in pneumonitis induced by BAs. AG administration as an antioxidant helps in recovery, both biochemically and histopathologically. Consequently, AG seems to be an alternative that should be considered in a conservative approach to treating aspiration pneumonitis.

Keywords: CC-16; aminoguanidine; aspiration pneumonitis; bile acids; gastroesophageal reflux.

Figure 1

Comparison of Clara cell protein 16 (CC-16) between groups. AG = aminoguanidine; BA = bile acids. *P = 0.002, compared with the saline group; ^†P = 0.001, compared with the BA group.

Figure 2

Comparison of (A) nitric oxide (NO) and (B) malondialdehyde (MDA) between groups. AG = aminoguanidine; BA = bile acids. *P = 0.017, compared with the saline group; ^†P = 0.003, compared with the BA group.

Figure 3

Comparison of quantities of (A) superoxide dismutase (SOD) and (B) glutathione peroxidase (GSH-Px) between groups. AG = aminoguanidine; BA = bile acids. *P = 0.003, compared with the saline group; ^†P = 0.002, compared with the BA group.

Figure 4

Images of histopathologic analysis (hematoxylin-eosin stain × 40). (A) Saline group, (B) saline + aminoguanidine group, (C) bile acid group, and (D) bile acid + aminoguanidine group. Almost normal lung parenchyma is monitored in A, B, and D similar to each other. There is an inflammatory cell infiltration in the peribronchial zones (star). The interalveolar zones are natural in general; slight inflammatory cell infiltration may be monitored in small focal zones. Significant inflammatory cell infiltration, thickening in interalveolar zones, and diffuse inflammation are observed in the peribronchial zones in the bile acid group.