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

Janice Drew, John Arthur, Andrew Farquharson, Wendy R Russell, P C Morrice, Garry G Duthie

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)888-893
Number of pages6
JournalBiochemical Pharmacology
Volume70
Issue number6
DOIs
Publication statusPublished - 15 Sep 2005

Keywords

  • glutathione peroxidase
  • colon cancer
  • damage
  • prostaglandins
  • nonsteroidal antiinflammatory drugs
  • selenium deficiency
  • cancer prevention
  • gene expression
  • oxide synthase
  • vitamin E
  • aspirin
  • selenoproteins
  • inhibition

Cite this

Salicylic acid modulates oxidative stress and glutathione peroxidase activity in the rat colon. / Drew, Janice; Arthur, John; Farquharson, Andrew; Russell, Wendy R; Morrice, P C; Duthie, Garry G.

In: Biochemical Pharmacology, Vol. 70, No. 6, 15.09.2005, p. 888-893.

Research output: Contribution to journalArticle

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AU - Drew, Janice

AU - Arthur, John

AU - Farquharson, Andrew

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AU - Duthie, Garry G

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N2 - 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.

AB - 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.

KW - glutathione peroxidase

KW - colon cancer

KW - damage

KW - prostaglandins

KW - nonsteroidal antiinflammatory drugs

KW - selenium deficiency

KW - cancer prevention

KW - gene expression

KW - oxide synthase

KW - vitamin E

KW - aspirin

KW - selenoproteins

KW - inhibition

U2 - 10.1016/j.bcp.2005.06.011

DO - 10.1016/j.bcp.2005.06.011

M3 - Article

VL - 70

SP - 888

EP - 893

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

IS - 6

ER -