Synergistic antioxidant and anti-inflammatory action of N-acetylcysteine in portal hypertensive gastropathy in rats

Abstract

Background and aim: Portal hypertension (PH) is a syndrome associated with cirrhosis and characterized by a progressive increase in portal pressure, with consequent compensatory vascular dilation. Gastric vascular changes associated with oxidative and nitrosative stress characterize the clinical presentation of portal hypertensive gastropathy (PHG). In addition, the inflammatory process is considered an aggravating factor for severity by contributing to gastric tissue injury. The aim of this study was to investigate the synergistic anti-inflammatory and antioxidant action of N-acetylcysteine (NAC) in the stomach of rats with PH.

Materials and methods: Eighteen Wistar male rats were used in this experimental protocol and were divided into three groups with six in each group: sham-operated (SO), partial portal vein ligation (PPVL), and PPVL + NAC. Treatment with NAC at a dose of 10 mg/kg (i.p.) was initiated on day 8 after surgery and continued for 7 days. We evaluated the expression of iNOS, NQO-1, HSP-90, and SOD by Western blot, as well as nuclear factor-kappa B (NF-κB) and tumor necrosis factor (TNF)-α staining by immunohistochemistry, in the rat stomach.

Results: The PPVL group exhibited increased expression of HSP-90, iNOS, SOD, and NQO-1 when compared with controls. NAC reduced the expression of all studied proteins. Similarly, NF-κB and TNF-α staining was increased in PPVL animals versus controls and reduced in PPVL + NAC versus PPVL animals, respectively.

Conclusion: These results suggest the effectiveness of NAC as a dual anti-inflammatory and antioxidant in animals with experimental PHG induced by partial ligation of the portal vein.

Keywords: Inflammation; N-acetylcysteine; oxidative stress; portal hypertension.

Figure 1.

Western blot for HSP90. Effects of PPVL and NAC administration on HSP90, quantified by the Western blot technique. *: P<0.01; **: P<0.01 (n=6); SO: Sham-operated group; PPVL: Partial portal vein ligation group; PPVL + NAC: Partial portal vein ligation group plus N-acetylcysteine treatment.

Figure 2.

Western blot for iNOS. Effects of PPVL and NAC administration on iNOS, quantified by the Western blot technique. *: P<0.01; **: P<0.05 (n=6).

Figure 3.

Western blot for SOD. Effects of PPVL and NAC administration on SOD, quantified by the Western blot technique. *: P<0.05; **: P<0.05 (n=6).

Figure 4.

Western blot for NQO1. Effects of PPVL and NAC administration on NQO1, quantified by the Western blot technique. *: P<0.05; **: P<0.05 (n=6).

Figure 5.

Immunohistochemical staining for NF-κB. Effects of PPVL and NAC administration on NF-κB expression. (a) SO group, (b) PPVL group, and (c) PPVL + NAC group. *: P<0.001 (n=6).

Figure 6.

Immunohistochemical staining for TNF-α. Effects of PPVL and NAC administration on TNF-α expression. (a) SO group, (b) PPVL group, and (c) PPVL + NAC group. *: P<0.001 (n=6).