title: Hesperidin alleviates oxidative stress and downregulates the expressions of proliferative and inflammatory markers in azoxymethane-induced experimental colon carcinogenesis in mice.
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.
  
  
  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.
  
  
  CONCLUSIONS
  This study proves the chemopreventive efficacy of hesperidin against the deleterious traits of colon carcinogenesis including accelerated proliferation, inflammation and persistent oxidative stress.
authors: Department of Biochemistry, Cell Biology Laboratory, University of Madras, Guindy Campus, Chennai 600025, Tamil Nadu, India.
authors: Gowrikumar
authors: G
authors: Saiprasad
authors: Palanivel
authors: P
authors: Chitra
authors: Ramar
authors: R
authors: Manikandan
authors: Ganapasam
authors: G
authors: Sudhandiran
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001397:Azoxymethane; D015415:Biomarkers / Q000378:metabolism; D002273:Carcinogens; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015536:Down-Regulation; D006569:Hesperidin / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D015415:Biomarkers; D002273:Carcinogens; D016328:NF-kappa B; D018809:Proliferating Cell Nuclear Antigen; D006569:Hesperidin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D001397:Azoxymethane
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