ABSTRACT
Nonsteroidal anti-inflammatory drugs [NSAIDs] possess anti-inflammatory, analgesic and antipyretic properties by inhibiting cyclooxygenase [COX] enzyme that exists in two isoforms, COX-1 and COX-2. Traditional nonsteroidal anti-inflammatory drugs [NSAIDs] inhibit both isoenzymes, resulting in damage to the mucosa of the stomach and duodenum. Rofecoxib [Vioxx] is a new generation NSAID, a cyclooxygenase [COX]-2 inhibitor that exhibits promising efficacy comparable with that of NSAIDs for relief of pain and inflammation in osteoarthritis, with decreased risk of gastrointestinal [GI] damage. Several investigators reported that COX-2 inhibitors would be a potential tool for the treatment and prevention of squamous cell carcinoma of the head and neck and are promising agents for the chemoprevention of prostate cancer. The present study aimed to investigate the effects of administration of variable doses of rofecoxib on the histology and the im-munohistochemical expression of COX-2 in different elements of the rat submandibular salivary gland. The animals were divided into five groups as follows; group I controls, groups II and IV received the minimum therapeutic doses of rofecoxib for one and four weeks respectively while groups III and V received the maximum therapeutic doses of rofecoxib for one and four weeks respectively. Results of the present investigation showed histological alterations in the acinar and ductal cells of the submandibular glands of animals in group II. Such alterations were more pronounced in glands of animals from group III who received the maximum dose for the same duration. A noticeable improvement in histological features was observed in submandibular glands from animals of group IV as compared to those of group II. On the other hand, the most pronounced histological changes were associated with the prolonged administration of the maximum dose as seen in submandibular specimens of group V.The Immunohistochemical results of the present work showed variable grades of positive expression of COX-2 in different elements of the submandibular gland of the control rats.On rofecoxib administration, the acinar cells showed redistribution of the COX-2 reactivity and reduced reaction in the connective tissue [CT] after one week administration of the minimum dose while the maximum dose for the same duration markedly inhibited the reaction in both. On the other hand, continued administration of the minimum dose for 4 weeks was associated with regain of the normal acinar and CT reactivity as that of the control. However, continued administration of the maximum dose for four weeks resulted in a reaction pattern similar to that of group III. The results were analyzed and discussed in view of the available literature. It was concluded that 1. Rofecoxibadministration dose dependently induced histological alterations in the submandibular gland. 2. Continued administration of the minimum dose of rofecoxib was associated with adaptive histological response while failure of such adaptation was seen on continued administration of the maxi-mum dose. 3. Changes in COX-2 expression in different elements of these glands seem to be reactionary and tissue specific