Hesperidin alleviates oxidative stress and downregulates the expressions of proliferative and inflammatory markers in az
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Inflammation Research
ORIGINAL RESEARCH PAPER
Hesperidin alleviates oxidative stress and downregulates the expressions of proliferative and inflammatory markers in azoxymethane-induced experimental colon carcinogenesis in mice Gowrikumar Saiprasad • Palanivel Chitra • Ramar Manikandan • Ganapasam Sudhandiran
Received: 15 November 2012 / Accepted: 8 January 2013 Ó Springer Basel 2013
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-jB), 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
Responsible Editor: Liwu Li. G. Saiprasad P. Chitra G. Sudhandiran (&) Department of Biochemistry, Cell Biology Laboratory, University of Madras, Guindy Campus, Chennai 600025, Tamil Nadu, India e-mail: [email protected]; [email protected] R. Manikandan Department of Animal Health and Management, Alagappa University, Karaikudi 630003, Tamil Nadu, India
administration. Hesperidin treatments caused a prominent downregulation of NF-jB 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. Keywords Hesperidin Colon carcinogenesis PCNA NF-jB COX-2 iNOS
Introduction Colon cancer ranks third amongst the most common fatal cancers in both men and women. Approximately 5 % of the western population develops colon malignancy during their lifetime. The statistics of colon cancer are sobering, with 101,340 new cases and 49,380 deaths in United States during 2011 [1]. Alarmingly, the incidence rate in south central Asia has been rising slowly during the last three decades [2]. Despite treatment with chemotherapy and surgery, death rates are high, together with adverse side effects [3]. The etiology of colon cancer is multifactorial; it occurs sporadically and is inherited in only 5 % of cases. A close associat
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