Salicylic acid modulates oxidative stress and glutathione peroxidase activity in the rat colon

Oxidative stress is a characteristic of cancerous colon tissue and inflammatory bowel diseases that increase colon cancer risk. Epidemiological evidence supports a protective effect of plant-derived compounds. Aspirin is also protective against colon cancer. The mechanism of action is unclear although salicylic acid, the main metabolite of aspirin, has been shown to decrease the synthesis of proinflammatory and potentially neo-plastic prostaglandins. Salicylic acid is found in significant quantities in a plant-based diet. However, in plants salicylic acid is also reported to modulate the expression of numerous enzymes with antioxidant activity. The aim of this study was to assess whether salicylic acid can modulate pro-cancerous biological pathways in the colon. Oxidative stress, prostaglandins and cytosolic glutathione peroxidase (cyGPX) were analysed in proximal, transverse and distal colon from a rat model of diet-induced oxidative stress. Elevated plasma pyruvate kinase activity (1293 +/- 206 U/ml) and increased indices of lipid peroxidation in colon (proximal 6.4 +/- 0.84 nM MDA/mg protein; transverse 6.9 +/- 0.97 nM MDA/mg protein; distal 5.2 +/- 0.62 nM MDA/mg protein) from rats fed a Vitamin E deficient diet were significantly decreased on supplementation with salicylic acid (plasma pyruvate 546 43 U/ml; salicylic acid proximal 3.6 +/- 0.39 nM MDA/mg protein; transverse 4.5 +/- 0.61 nM MDA/mg protein; distal 4.4 +/- 0.27 nM MDA/mg protein). Reductions in oxidative stress and prostaglandin production on supplementation with salicylic acid were associated with an elevation in glutathione peroxidase activity (Vitamin E deficient proximal 0.056 +/- 0.013 U/mg protein; transverse 0.073 +/- 0.008 U/mg protein; distal 0.088 +/- 0.010 U/mg protein; Vitamin E deficient with salicylic acid proximal 0.17 +/- 0.01 U/mg protein; transverse 0.23 +/- 0.016 U/mg protein; distal 0.16 +/- 0.020 U/mg protein). Gpx1 and Gpx2 gene transcripts were not elevated in association with increased activity of the soluble glutathione peroxidase activity. Glutathione peroxidases are key antioxidant enzymes, catalysing the decomposition of potentially toxic lipid peroxides. Gpx activity and regulation of Gpx gene transcription has been shown previously to be complex with activity not necessarily mirrored by a corresponding elevation in gene transcription. By supplementing the diet of Vitamin E deficient rats with salicylic acid (1 g/kg diet), this study assessed effects of salicylic acid on cytosolic glutathione peroxidase activity in the colon. The ability of salicylic acid to modulate antioxidant enzymes in colon tissue may be an important mechanism in inhibiting colon cancer development. (c) 2005 Elsevier Inc. All rights reserved.