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Hesperidin alleviates oxidative stress and downregulates the expressions of proliferative and inflammatory markers in azoxymethane-induced experimental colon carcinogenesis in mice

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Abstract

Objective

Colon cancer is a common malignant neoplasm causing huge morbidity and mortality worldwide. Current therapeutic interventions are unsatisfying, which necessitates novel chemopreventive strategies. The present study was intended to elucidate the chemopreventive efficacy of hesperidin against azoxymethane (AOM)-induced mouse colon carcinogenesis.

Materials and methods

Swiss albino mice were subjected to intraperitoneal injections of AOM once a week for 3 consecutive weeks. Hesperidin treatments were provided in the initiation or post-initiation phases. The number and multiplicity of aberrant crypt foci (ACF), tumor incidence and antioxidant status were determined. Histopathological analyses, proliferating cell nuclear antigen (PCNA) index and modulations in the expression of inflammatory markers such as nuclear factor kappa B (NF-κB), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were studied.

Results

Hesperidin treatments significantly inhibited the number and multiplicities of AOM-induced ACF and tumor incidence. Hesperidin reduced oxidative stress parameters and enhanced antioxidant status. A marked decrease in the PCNA index was evident on hesperidin administration. Hesperidin treatments caused a prominent downregulation of NF-κB and its target molecules iNOS and COX-2, thereby combating inflammation.

Conclusion

This study proves the chemopreventive efficacy of hesperidin against the deleterious traits of colon carcinogenesis including accelerated proliferation, inflammation and persistent oxidative stress.

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Acknowledgments

This work was supported by a fund from the Council of Scientific and Industrial Research (CSIR), New Delhi. We thank Dr. Ramamurthy, Director, Ultra-fast Process Laboratory, University of Madras for his help in confocal imaging.

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Authors and Affiliations

  1. Department of Biochemistry, Cell Biology Laboratory, University of Madras, Guindy Campus, Chennai, 600025, Tamil Nadu, India

    Gowrikumar Saiprasad, Palanivel Chitra & Ganapasam Sudhandiran

  2. Department of Animal Health and Management, Alagappa University, Karaikudi, 630003, Tamil Nadu, India

    Ramar Manikandan

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  1. Gowrikumar Saiprasad
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  2. Palanivel Chitra
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  3. Ramar Manikandan
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  4. Ganapasam Sudhandiran
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Correspondence to Ganapasam Sudhandiran.

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Responsible Editor: Liwu Li.

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Saiprasad, G., Chitra, P., Manikandan, R. et al. Hesperidin alleviates oxidative stress and downregulates the expressions of proliferative and inflammatory markers in azoxymethane-induced experimental colon carcinogenesis in mice. Inflamm. Res. 62, 425–440 (2013). https://doi.org/10.1007/s00011-013-0595-2

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