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Abstract Aim: This study aimed to compare the effect of different thymoquinone preparations, as chemopreventive agents on the activation of nuclear factor-κB (NF-B) in hamster buccal pouch/7,12-dimethylbenz(a)-anthracene (HBP/DMBA) experimental model. Material and Methods: One hundred and sixty fife male Syrian golden hamsters were divided into 3 groups: group A: A-1 (15 animals) served as negative control, and A-2 (10 animals) left buccal pouches were painted 3/week with the carcinogen (0.5% DMBA in heavy mineral oil) 3/week for 7&14 weeks. group B: 70 animals were daily painted by topical application of TQ (0.05, 0.01, and 0.001 mg/kg), G NP, and G NP-TQ (0.05, 0.01, and 0.001 mg/kg) for 2weeks into the left pouches, then with both chemopreventive drugs & DMBA for 7&14weeks on alternative days. group C: (70 animals) subdivided as group B and treated with chemopreventive drugs only, and served as self-control. Complete blood counting and liver & kidney enzymes were done. The treated left buccal pouches were surgically excised, fixed, and processed for H&E stain, and NK-B immunohistochemistry. Results: Groups A1, and C showed normal blood values, with increased lymphocyte % in group C. group A2showed decreased lymphocyte %, and elevated liver enzymes. group B showed elevated lymphocyte %, and saved liver & kidney enzymes. Histopathological and immunohistochemical results: groups A1, and C showed normal HBP histology, and negative NK-B immunoreactivity. group A2 showed severe dysplasia at 7weeks, well to moderate SCC at 14 weeks, and intense NK-B immunoreactivity in all cases. Groups TQ 0.05, G NP, and G NP-TQ 0.05 showed severe dysplasia at 7weeks, CIS & superficial invasion at 14 weeks, and intense NK-B immunoreactivity. Groups TQ 0.01, and TQ 0.001 showed moderate dysplasia at 7weeks, CIS & superficial invasion at 14 weeks, with moderate NK-B immunoreactivity at 7 weeks, with intense NK-B immunoreactivity at 14weeks. group G NP-TQ 0.01 showed mild to moderate dysplasia 7weeks, CIS & superficial invasion at 14 weeks, and moderate NK-B immunoreactivity. G NP-TQ 0.001 showed mild dysplasia at 7weeks, CIS at 14 weeks, and mild NK-B immunoreactivity. Conclusion: Topical painting of GNPs was shown to penetrate through whole epithelium thickness up to the muscle layer. G NP-TQ 0.001 topical chemoprevention was found to successfully retard HBP/DMBA carcinogenesis, improving the general animal health, restoration of lymphocytes %, as well as inhibition of NK-B expression, and finally was able to regenerate the striated muscle layer to near length. |