الفهرس 
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Abstract
It aimed to study cyclooxygenase-2 (Cox-2) expression in hamster buccal pouch/ 7, 12-dimethylbenz(a)-anthracene (HBP/DMBA) experimental model, following topical application of thymoquinone loaded on gold nanoparticles (GNPs-TQ) as chemopreventive agent.
Archival paraffin blocks represented buccal pouches of 85 male Syrian golden hamsters. These blocks followed the animals‟ protocol of treatment and were divided into 2 groups: A: Control groups and B: Experimental groups. The control groups included I, II, III, IV and V. I: negative control group (15 animals), sacrificed at day zero then after 7 and 14 weeks (5 animals each). II: (10 animals) painted topically with DMBA on left pouches 3 times / week for 7 and 14 weeks (5 animals each). III: (10 animals) painted topically with TQ (0.001mg/kg) on left pouches as group II (5 animals each). IV: (10 animals) painted topically with G-NPs on left pouches as group II (5 animals each).V: (10 animals) painted topically with 0.001mg/kg TQ loaded on G-NPs on left pouches as group II (5 animals each).
The experimental groups: included VI, VII and VIII (10 animals each) were treated with the chemopreventive agents. VI: painted daily and topically with TQ (0.001mg/kg) for 2 weeks and then with both TQ (0.001mg/kg) and DMBA on alternative days for 7 and 14 weeks. VII: painted daily and topically with G-NPs for 2 weeks and then with both G- NPs and DMBA as group VI. VIII: painted daily and topically with TQ (0.001mg/kg) loaded on G-NPs for 2 weeks and then with both TQ (0.001mg/kg) loaded on G-NPs and DMBA as group VI. Both buccal pouches were surgically excised, fixed and processed for H&E stain and Cox-2 immunohistochemistry (IHC).
Results: Negative, self-control groups (I, III, IV and V), and right pouches of all experimental groups, showed normal appearing HBP mucosa and negative COX-2 immunoreactivity. group II showed severe dysplasia at 7 weeks, well to moderate SCC at 14 weeks and intense Cox-2 immunoreactivity at both 7 and 14 weeks. Indicating the COX-2 activation by DMBA (carcinogenesis process). group VI (TQ 0.001/DMBA) showed
moderate dysplasia with moderate Cox-2 immunoreactivity at 7 weeks, while at 14 weeks showed CIS and superficial invasion with intense Cox-2 immunoreactivity. group VII (G-NPs / DMBA) showed moderate to severe dysplasia with moderate Cox-2 immunoreactivity at 7 weeks, while at 14 weeks showed CIS and superficial invasion with intense Cox-2 immunoreactivity. Indicating that TQ or G-NPs alone had less protective effect on this process, mostly due to its known poor bioavailability, when used topically. While group VIII (G-NPs-TQ 0.001/DMBA) showed mild dysplasia with mild Cox-2 immunoreactivity at 7 weeks, while at 14 weeks showed mild to moderate dysplasia with focal areas of CIS, and moderate Cox-2 immunoreactivity. Indicating the best TQ protective effect, facilitated by its loading on G-NPs, for intracellular penetration to excert its anti- inflammatory and free radicle scavenging effects.