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Carnosic acid: A potent chemopreventive agent against oral carcinogenesis
Authors:Shanmugam Manoharan  MuthamizhSelvan VasanthaSelvan  Simon Silvan  Nagarethinam Baskaran  Arjun Kumar Singh  Veerasamy Vinoth Kumar
Institution:1. Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608 002, Tamil Nadu, India;2. Department of Pathology, Rajah Muthiah Medical College, Annamalai University, Annamalainagar 608 002, Tamil Nadu, India;3. Faculty of Marine Sciences, Centre for Advanced Study in Marine Biology, Annamalai University, Parangipettai 608 502, Tamil Nadu, India;1. Laboratory of Plant Biochemistry, Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas Buenos Aires I.I.B.B.A-CONICET, Ciudad Autónoma de Buenos Aires, Argentina;2. Pharmacognosy-IQUIMEFA-(UBA-CONICET)-Facultad de Farmacia y Bioquímica-Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina;3. Laboratory of Nuclear Architecture, Instituto de Biología y Medicina Experimental, CONICET, Ciudad Autónoma de Buenos Aires, Argentina
Abstract:The present study was aimed to investigate the chemopreventive potential of carnosic acid in 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. The chemopreventive potential was assessed by analyzing the tumor incidence, tumor volume and burden as well as by measuring the status of lipid peroxidation, non-enzymatic and enzymatic antioxidants and phase I and phase II detoxification enzymes. Oral squamous cell carcinoma 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. In the present study, 100% tumor formation was observed in hamsters treated with DMBA alone. Also, the status of lipid peroxidation, antioxidants and phase I and phase II detoxification enzymes were significantly altered during DMBA-induced oral carcinogenesis. Oral administration of carnosic acid at a dose of 10 mg/kg body weight/day to DMBA-treated animals completely prevented the tumor formation in the hamsters’ buccal pouches. Also, carnosic acid exerted potent anti-lipid peroxidative function and stimulated the detoxification cascade during DMBA-induced hamster buccal pouch carcinogenesis. The results of the present study suggest that the chemopreventive potential of carnosic acid is probably due to its anti-lipid peroxidative potential and modulating effect on carcinogen detoxification enzymes during DMBA-induced oral carcinogenesis.
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