Chemopreventive Efficacy of Naringenin-Loaded Nanoparticles in 7,12-dimethylbenz(a)anthracene Induced Experimental Oral
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RESEARCH
Chemopreventive Efficacy of Naringenin-Loaded Nanoparticles in 7,12-dimethylbenz(a)anthracene Induced Experimental Oral Carcinogenesis Nechikkad Sulfikkarali & Narendran Krishnakumar & Shanmugam Manoharan & Ramadas Madhavan Nirmal
Received: 1 June 2012 / Accepted: 6 November 2012 / Published online: 12 December 2012 # Arányi Lajos Foundation 2012
Abstract Nanochemoprevention has been introduced recently as a novel approach for improving phytochemicals bioavailability and anti-tumor effect. The present study is designed to evaluate the chemopreventive efficacy of prepared naringenin-loaded nanoparticles (NARNPs) relative to efficacy of free naringenin (NAR) against 7,12-dimethyl benz(a)anthracene (DMBA)-induced oral carcinogenesis by evaluating the status of lipid peroxidation, antioxidants and immunoexpression patterns of proliferating cell nuclear antigen (PCNA) and p53 proteins. Transmission electron microscope (TEM) and dynamic light scattering (DLS) investigations have confirmed a narrow size distribution of the prepared nanoparticles (40–90 nm) with ~88 % encapsulation efficiency. Oral squamous cell carcinoma (OSCC) was developed in the buccal pouch of golden Syrian hamsters by painting with 0.5 % DMBA in liquid paraffin three times a week for 14 weeks. DMBA painted animals revealed the morphological changes, hyperplasia, dysplasia and welldifferentiated squamous cell carcinoma. Moreover, the status of lipid peroxidation, antioxidants and immunoexpression of PCNA and p53 were significantly altered during DMBA-induced oral carcinogenesis. Oral administration of NARNPs (50 mg NAR/kg body weight/day) to DMBAtreated animals completely prevented the tumor formation N. Sulfikkarali : N. Krishnakumar (*) Department of Physics, Annamalai University, Annamalainagar 608 002, Tamilnadu, India e-mail: [email protected] S. Manoharan Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar 608 002, Tamilnadu, India R. M. Nirmal Department of Oral and Maxillofacial Pathology, Rajah Muthiah Dental College & Hospital, Annamalai University, Annamalainagar 608 002, Tamilnadu, India
as compared to the free NAR and significantly reduced the degree of histological lesions, in addition to restoration of the status of biochemical and molecular markers during oral carcinogenesis. In addition, NARNPs have more potent anti-lipid peroxidative, antiproliferative effect and antioxidant potentials compared to free NAR in DMBA-induced oral carcinogenesis. In conclusion, the present study suggests that NARNPs could be a potentially useful drug carrier system for targeted delivery of naringenin for cancer chemoprevention. Keywords Nanochemoprevention . DMBA . Hamster buccal pouch carcinogenesis . Naringenin
Introduction Oral cancer is one of the most common malignancies and is a major cause of cancer morbidity and mortality worldwide. Globally, about 500,000 new cases of oral cancer are diagnosed annually and approximately 75 % of these occur in developing countries. Oral cancer accounts for 40–50 %
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