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

• Published in: Inflammation research 2013-04, Vol.62 (4), p.425-440
• Main Authors: Saiprasad, Gowrikumar, Chitra, Palanivel, Manikandan, Ramar, Sudhandiran, Ganapasam
• Format: Article
• Language: English
• Subjects: Allergology; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Azoxymethane; Biomarkers - metabolism; Biomedical and Life Sciences; Biomedicine; Carcinogens; Cell Proliferation - drug effects; Colonic Neoplasms - chemically induced; Colonic Neoplasms - drug therapy; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Cyclooxygenase 2 - metabolism; Dermatology; Down-Regulation; Hesperidin - pharmacology; Hesperidin - therapeutic use; Immunology; Inflammation - drug therapy; Inflammation - metabolism; Inflammation - pathology; Male; Mice; Neurology; NF-kappa B - metabolism; Nitric Oxide Synthase Type II - metabolism; Original Research Paper; Oxidative Stress - drug effects; Pharmacology/Toxicology; Proliferating Cell Nuclear Antigen - metabolism; Rheumatology
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/s00011-013-0595-2

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.