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References

  1. Aebi H. 1974. In Bergmeyer HU (ed.). Methods of Enzymatic Analysis, pp. 674-678. Academic Press, New York.
  2. Ajaikumar BK, Sushovan G, Sunil K, Parmeswaran D, Juri G, Bharat BA. 2007. Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-κB-regulated gene products. Cancer Res. 67: 3853-3861.
    Pubmed CrossRef
  3. Ashish MK, Gautam S, Bharat BA. 2007. Curcumin potentiates the apoptosis effects of chemotherapeutic agents and cytokines through down-regulation of nuclear factor-κB and nuclear factor-κB-regulated gene products in IFN-αsensitive and IFN-α-resistant human bladder cancer cells. Mol. Cancer Ther. 6: 1022-1030.
    Pubmed CrossRef
  4. Beck WS, Schneider HT, Dietzel K, Nuernberg B, Brune K. 1990. Gastrointestinal ulcerations induced by anti-inflammatory drugs in rats. Arch. Toxicol. 64: 210-217.
    Pubmed CrossRef
  5. Calhoun W, Gilman SC, Datko LJ, Copenhaver TW, Carlson RP. 1992. Interaction studies of tilomisole, aspirin and naproxen in acute and chronic inflammation with assessment of gastrointestinal irritancy in the rat. Agents Actions 36: 99-106.
    Pubmed CrossRef
  6. Cioli V, Putzolu S, Rossi V, Scorza BP, Corradino C. 1979. The role of direct tissue contact in the production of gastrointestinal ulcers by anti-inflammatory drugs in rats. Toxicol. Appl. Pharmacol. 50: 283-289.
    CrossRef
  7. Glienke W, Maute L, Wicht J, Bergmann L. 2009. Wilms’ tumour gene 1 (WT1) as a target in curcumin treatment of pancreatic cancer cells. Eur. J. Cancer 45: 874-880.
    Pubmed CrossRef
  8. Half E, Arber N. 2009. Colon cancer: preventive agents and the present status of chemoprevention. Expert Opin. Pharmacother. 10: 211-219.
    Pubmed CrossRef
  9. Hogeboom GH. 1955. In Colowick SP, Kaplan NO (eds.). Methods in Enzymology, pp. 16-19. Academic Press, New York.
  10. Huang MT, Lysz T, Ferraro T, Abidi TF, Laskin JD, Conney AH. 1991. Inhibitory effects of curcumin on in vitro lipoxygenase and cyclooxygenase activities in mouse epidermis. Cancer Res. 51: 813-819.
    Pubmed
  11. Jiao Y, Wilkinson J 4th, Di X, Wang W, Hatcher H, Kock ND, et al. 2009. Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator. Blood 113: 462-469.
    Pubmed PMC CrossRef
  12. Kang J, Chen J, Shi Y, Jia J, Zhang Y. 2005. Curcumininduced histone hypoacetylation: the role of reactive oxygen species. Biochem. Pharmacol. 69: 1205-1213.
    Pubmed CrossRef
  13. Kim JH, Kim YS, Song GG, Park JJ, Chang HI. 2005. Protective effect of astaxanthin on naproxen-induced gastric antral ulceration in rats. Eur. J. Pharmacol. 514: 53-59.
    Pubmed CrossRef
  14. Krishnan MD, Virendra BM, Darrell WB. 2007. Curcumin suppresses growth and chemoresistance of human glioblastoma cells via AP-1 and NF-κB transcription factors. J. Neurochem. 102: 522-538.
    Pubmed CrossRef
  15. Lawrence RA, Burk RF. 1976. Glutathione peroxidase activity in selenium-deficient rat liver. Biochem. Biophys. Res. Commun. 71: 952-958.
    CrossRef
  16. Lin YG, Kunnumakkara AB, Nair A, Merritt WM, Han LY, Armaiz-Pena GN, et al. 2007. Curcumin inhibits tumor growth and angiogenesis in ovarian carcinoma by targeting the nuclear factor-κB pathway. Clin. Cancer. Res. 13: 3423-3430.
    Pubmed CrossRef
  17. Liu E, Wu J, Cao W, Zhang J, Liu W, Jiang X, Zhang X. 2007. Curcumin induces G2/M cell cycle arrest in a p53dependent manner and upregulates ING4 expression in human glioma. J. Neurooncol. 85: 263-270.
    Pubmed CrossRef
  18. Lodha R, Bagga A. 2000. Traditional Indian systems of medicine. Ann. Acad. Med. Singapore 29: 37-41.
    Pubmed
  19. McCarthy DM. 1990. NSAID-induced gastro-intestinal damage - a critical review of prophylaxis and therapy. J. Clin. Gastroenterol. 12: S13-S20.
    Pubmed CrossRef
  20. McCarthy DM. 1995. Mechanisms of mucosal injury and healing: the role of nonsteroidal anti-inflammatory drugs. Scand. J. Gastroenterol. 208: 24-29.
    CrossRef
  21. McCord JM, Fridovich I. 1967. Superoxide dismutase, an enzymatic function for erythrocuprein (hemocuprein). J. Biol. Chem. 244: 6049-6055.
  22. Milacic V, Banerjee S, Landis-Piwowar KR, Sarkar FH, Majumdar AP, Dou QP. 2008. Curcumin inhibits the proteasome activity in human colon cancer cells in vitro and in vivo. Cancer Res. 68: 7283-7292.
    Pubmed PMC CrossRef
  23. Ohkawa H, Ohishi N, Yagi K. 1979. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem. 95: 351-358.
    CrossRef
  24. Parks DA. 1989. Oxygen radicals: mediators of gastrointestinal pathophysiology. Gut 30: 293-298.
    Pubmed PMC CrossRef
  25. Roth SH, Bennett RE. 1987. Non-steroidal anti-inflammatory drug gastropathy: recognition and response. Arch. Intern. Med. 147: 2093-2100.
    Pubmed CrossRef
  26. Ruby AJ, Kuttan G, Babu KD, Rajasekharan KN, Kuttan R. 1995. Anti-tumour and antioxidant activity of natural curcuminoids. Cancer Lett. 94: 79-83.
    CrossRef
  27. Salvioli S, Sikora E, Cooper EL, Franceschi C. 2007. Curcumin in cell death processes: a challenge for CAM of age-related pathologies. Evid. Based Complement. Alternat. Med. 4: 181-190.
    Pubmed PMC CrossRef
  28. Sankar B, Debaprasad M, Baisakhi S, Gouri SS, Tanya D, Gaurisankar S. 2007. Curcumin prevents tumor-induced T cell apoptosis through Stat-5a-mediated Bcl-2 induction. J. Biol. Chem. 282: 15954-15964.
    Pubmed CrossRef
  29. Shishodia S, Sethi G, Aggarwal BB. 2005. Curcumin: getting back to the roots. Ann. NY Acad. Sci. 1056: 206-217.
    Pubmed CrossRef
  30. Surajit K, Naren LB, Swapan KR. 2007. Curcumin suppressed anti-apoptotic signals and activated cysteine proteases for apoptosis in human malignant glioblastoma U87MG cells. Neurochem. Res. 32: 2103-2113.
    Pubmed CrossRef
  31. Suwa T, Urano H, Kohno Y, Suzuki A, Amano T. 1987. Comparative studies on the gastrointestinal lesions caused by several nonsteroidal anti-inflammatory agents in rats. Agents Actions 21: 167-172.
    Pubmed CrossRef
  32. Swamy MV, Citineni B, Patlolla JM, Mohammed A, Zhang Y, Rao CV. 2008. Prevention and treatment of pancreatic cancer by curcumin in combination with omega-3 fatty acids. Nutr. Cancer 60: 81-89.
    Pubmed CrossRef
  33. Thiyagarajan M, Sharma SS. 2004. Neuroprotective effect of curcumin in middle cerebral artery occlusion induced focal cerebral ischemia in rats. Life Sci. 74: 969-985.
    Pubmed CrossRef
  34. Wang Q, Sun AY, Simonyi A, Jensen MD, Shelat PB, Rottinghaus GE, et al. 2005. Neuroprotective mechanisms of curcumin against cerebral ischemia-induced neuronal apoptosis and behavioral deficits. J. Neurosci. Res. 82: 138-148.
    Pubmed CrossRef
  35. Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS, et al. 2005. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J. Biol. Chem. 280: 5892-5901.
    Pubmed CrossRef
  36. Yoshikawa T, Naito Y, Ueda S, Oyamada H, Takemura T, Yoshida N, et al. 1990. Role of oxygen-derived free radicals in the pathogenesis of gastric mucosal lesions in rats. J. Clin. Gastroenterol. 12: 65-71.
    CrossRef
  37. Yu Z, Shah DM. 2007. Curcumin down-regulates Ets-1 and Bcl-2 expression in human endometrial carcinoma HEC-1-A cells. Gynecol. Oncol. 103: 541-548.
    Pubmed CrossRef

Article

Research article

J. Microbiol. Biotechnol. 2016; 26(8): 1392-1397

Published online August 28, 2016 https://doi.org/10.4014/jmb.1602.02028

Copyright © The Korean Society for Microbiology and Biotechnology.

Curcumin Blocks Naproxen-Induced Gastric Antral Ulcerations through Inhibition of Lipid Peroxidation and Activation of Enzymatic Scavengers in Rats

Jeong-Hwan Kim 1, Soojung Jin 1, Hyun Ju Kwon 1, 2 and Byung Woo Kim 1, 2*

1Blue-Bio Industry RIC, Dong-Eui University, Busan 47340, Republic of Korea, 2Department of Life Science and Biotechnology, Dong-Eui University, Busan 47340, Republic of Korea

Received: February 15, 2016; Accepted: May 19, 2016

Abstract

Curcumin is a polyphenol derived from the plant Curcuma longa, which is used for the
treatment of diseases associated with oxidative stress and inflammation. The present study
was undertaken to determine the protective effect of curcumin against naproxen-induced
gastric antral ulcerations in rats. Different doses (10, 50, and 100 mg/kg) of curcumin or
vehicle (curcumin, 0 mg/kg) were pretreated for 3 days by oral gavage, and then gastric
mucosal lesions were caused by 80 mg/kg naproxen applied for 3 days. Curcumin
significantly inhibited the naproxen-induced gastric antral ulcer area and lipid peroxidation in
a dose-dependent manner. In addition, curcumin markedly increased activities of radical
scavenging enzymes, such as superoxide dismutase (SOD), catalase, and glutathione
peroxidase in a dose-dependent manner. Specifically, 100 mg/kg curcumin completely
protected the gastric mucosa against the loss in the enzyme, resulting in a drastic increase of
activities of radical scavenging enzymes up to more than the level of untreated normal rats.
Histological examination obviously showed that curcumin prevents naproxen-induced gastric
antral ulceration as a result of direct protection of the gastric mucosa. These results suggest
that curcumin blocks naproxen-induced gastric antral ulcerations through prevention of lipid
peroxidation and activation of radical scavenging enzymes, and it may offer a potential
remedy of gastric antral ulcerations.

Keywords: Curcumin, Gastric antral ulceration, Lipid peroxidation, Naproxen, Oral gavage, Radical scavenging enzymes

References

  1. Aebi H. 1974. In Bergmeyer HU (ed.). Methods of Enzymatic Analysis, pp. 674-678. Academic Press, New York.
  2. Ajaikumar BK, Sushovan G, Sunil K, Parmeswaran D, Juri G, Bharat BA. 2007. Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-κB-regulated gene products. Cancer Res. 67: 3853-3861.
    Pubmed CrossRef
  3. Ashish MK, Gautam S, Bharat BA. 2007. Curcumin potentiates the apoptosis effects of chemotherapeutic agents and cytokines through down-regulation of nuclear factor-κB and nuclear factor-κB-regulated gene products in IFN-αsensitive and IFN-α-resistant human bladder cancer cells. Mol. Cancer Ther. 6: 1022-1030.
    Pubmed CrossRef
  4. Beck WS, Schneider HT, Dietzel K, Nuernberg B, Brune K. 1990. Gastrointestinal ulcerations induced by anti-inflammatory drugs in rats. Arch. Toxicol. 64: 210-217.
    Pubmed CrossRef
  5. Calhoun W, Gilman SC, Datko LJ, Copenhaver TW, Carlson RP. 1992. Interaction studies of tilomisole, aspirin and naproxen in acute and chronic inflammation with assessment of gastrointestinal irritancy in the rat. Agents Actions 36: 99-106.
    Pubmed CrossRef
  6. Cioli V, Putzolu S, Rossi V, Scorza BP, Corradino C. 1979. The role of direct tissue contact in the production of gastrointestinal ulcers by anti-inflammatory drugs in rats. Toxicol. Appl. Pharmacol. 50: 283-289.
    CrossRef
  7. Glienke W, Maute L, Wicht J, Bergmann L. 2009. Wilms’ tumour gene 1 (WT1) as a target in curcumin treatment of pancreatic cancer cells. Eur. J. Cancer 45: 874-880.
    Pubmed CrossRef
  8. Half E, Arber N. 2009. Colon cancer: preventive agents and the present status of chemoprevention. Expert Opin. Pharmacother. 10: 211-219.
    Pubmed CrossRef
  9. Hogeboom GH. 1955. In Colowick SP, Kaplan NO (eds.). Methods in Enzymology, pp. 16-19. Academic Press, New York.
  10. Huang MT, Lysz T, Ferraro T, Abidi TF, Laskin JD, Conney AH. 1991. Inhibitory effects of curcumin on in vitro lipoxygenase and cyclooxygenase activities in mouse epidermis. Cancer Res. 51: 813-819.
    Pubmed
  11. Jiao Y, Wilkinson J 4th, Di X, Wang W, Hatcher H, Kock ND, et al. 2009. Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator. Blood 113: 462-469.
    Pubmed KoreaMed CrossRef
  12. Kang J, Chen J, Shi Y, Jia J, Zhang Y. 2005. Curcumininduced histone hypoacetylation: the role of reactive oxygen species. Biochem. Pharmacol. 69: 1205-1213.
    Pubmed CrossRef
  13. Kim JH, Kim YS, Song GG, Park JJ, Chang HI. 2005. Protective effect of astaxanthin on naproxen-induced gastric antral ulceration in rats. Eur. J. Pharmacol. 514: 53-59.
    Pubmed CrossRef
  14. Krishnan MD, Virendra BM, Darrell WB. 2007. Curcumin suppresses growth and chemoresistance of human glioblastoma cells via AP-1 and NF-κB transcription factors. J. Neurochem. 102: 522-538.
    Pubmed CrossRef
  15. Lawrence RA, Burk RF. 1976. Glutathione peroxidase activity in selenium-deficient rat liver. Biochem. Biophys. Res. Commun. 71: 952-958.
    CrossRef
  16. Lin YG, Kunnumakkara AB, Nair A, Merritt WM, Han LY, Armaiz-Pena GN, et al. 2007. Curcumin inhibits tumor growth and angiogenesis in ovarian carcinoma by targeting the nuclear factor-κB pathway. Clin. Cancer. Res. 13: 3423-3430.
    Pubmed CrossRef
  17. Liu E, Wu J, Cao W, Zhang J, Liu W, Jiang X, Zhang X. 2007. Curcumin induces G2/M cell cycle arrest in a p53dependent manner and upregulates ING4 expression in human glioma. J. Neurooncol. 85: 263-270.
    Pubmed CrossRef
  18. Lodha R, Bagga A. 2000. Traditional Indian systems of medicine. Ann. Acad. Med. Singapore 29: 37-41.
    Pubmed
  19. McCarthy DM. 1990. NSAID-induced gastro-intestinal damage - a critical review of prophylaxis and therapy. J. Clin. Gastroenterol. 12: S13-S20.
    Pubmed CrossRef
  20. McCarthy DM. 1995. Mechanisms of mucosal injury and healing: the role of nonsteroidal anti-inflammatory drugs. Scand. J. Gastroenterol. 208: 24-29.
    CrossRef
  21. McCord JM, Fridovich I. 1967. Superoxide dismutase, an enzymatic function for erythrocuprein (hemocuprein). J. Biol. Chem. 244: 6049-6055.
  22. Milacic V, Banerjee S, Landis-Piwowar KR, Sarkar FH, Majumdar AP, Dou QP. 2008. Curcumin inhibits the proteasome activity in human colon cancer cells in vitro and in vivo. Cancer Res. 68: 7283-7292.
    Pubmed KoreaMed CrossRef
  23. Ohkawa H, Ohishi N, Yagi K. 1979. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem. 95: 351-358.
    CrossRef
  24. Parks DA. 1989. Oxygen radicals: mediators of gastrointestinal pathophysiology. Gut 30: 293-298.
    Pubmed KoreaMed CrossRef
  25. Roth SH, Bennett RE. 1987. Non-steroidal anti-inflammatory drug gastropathy: recognition and response. Arch. Intern. Med. 147: 2093-2100.
    Pubmed CrossRef
  26. Ruby AJ, Kuttan G, Babu KD, Rajasekharan KN, Kuttan R. 1995. Anti-tumour and antioxidant activity of natural curcuminoids. Cancer Lett. 94: 79-83.
    CrossRef
  27. Salvioli S, Sikora E, Cooper EL, Franceschi C. 2007. Curcumin in cell death processes: a challenge for CAM of age-related pathologies. Evid. Based Complement. Alternat. Med. 4: 181-190.
    Pubmed KoreaMed CrossRef
  28. Sankar B, Debaprasad M, Baisakhi S, Gouri SS, Tanya D, Gaurisankar S. 2007. Curcumin prevents tumor-induced T cell apoptosis through Stat-5a-mediated Bcl-2 induction. J. Biol. Chem. 282: 15954-15964.
    Pubmed CrossRef
  29. Shishodia S, Sethi G, Aggarwal BB. 2005. Curcumin: getting back to the roots. Ann. NY Acad. Sci. 1056: 206-217.
    Pubmed CrossRef
  30. Surajit K, Naren LB, Swapan KR. 2007. Curcumin suppressed anti-apoptotic signals and activated cysteine proteases for apoptosis in human malignant glioblastoma U87MG cells. Neurochem. Res. 32: 2103-2113.
    Pubmed CrossRef
  31. Suwa T, Urano H, Kohno Y, Suzuki A, Amano T. 1987. Comparative studies on the gastrointestinal lesions caused by several nonsteroidal anti-inflammatory agents in rats. Agents Actions 21: 167-172.
    Pubmed CrossRef
  32. Swamy MV, Citineni B, Patlolla JM, Mohammed A, Zhang Y, Rao CV. 2008. Prevention and treatment of pancreatic cancer by curcumin in combination with omega-3 fatty acids. Nutr. Cancer 60: 81-89.
    Pubmed CrossRef
  33. Thiyagarajan M, Sharma SS. 2004. Neuroprotective effect of curcumin in middle cerebral artery occlusion induced focal cerebral ischemia in rats. Life Sci. 74: 969-985.
    Pubmed CrossRef
  34. Wang Q, Sun AY, Simonyi A, Jensen MD, Shelat PB, Rottinghaus GE, et al. 2005. Neuroprotective mechanisms of curcumin against cerebral ischemia-induced neuronal apoptosis and behavioral deficits. J. Neurosci. Res. 82: 138-148.
    Pubmed CrossRef
  35. Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS, et al. 2005. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J. Biol. Chem. 280: 5892-5901.
    Pubmed CrossRef
  36. Yoshikawa T, Naito Y, Ueda S, Oyamada H, Takemura T, Yoshida N, et al. 1990. Role of oxygen-derived free radicals in the pathogenesis of gastric mucosal lesions in rats. J. Clin. Gastroenterol. 12: 65-71.
    CrossRef
  37. Yu Z, Shah DM. 2007. Curcumin down-regulates Ets-1 and Bcl-2 expression in human endometrial carcinoma HEC-1-A cells. Gynecol. Oncol. 103: 541-548.
    Pubmed CrossRef