Histopathology of Gastric lesions
Histological assessment of gastric mucosa as shown in figure 5A illustrates a normal gastric architecture in untreated control animals. Treatment with ethanol triggered mucosal erosions and marked appearance of hemorrhage, with sub mucosal inflammation and infiltration of neutrophils resulting in the formation of gastric lesions, with detachment of the surface epithelium and loss of glandular cells (Fig. 5 B). Pretreatment with topiramate considerably reduced these changes in the gastric mucosa, and provided a gastro protective effect against ethanol induced gastric lesions (Fig 5 C-E). Topiramate treatment (100mg/Kg and 200mg /Kg) resulted in a clear gastric mucosal structure, with minimum or negligible infiltration of inflammatory cells and a substantial improvement in the glandular structure and arrangement (Fig 5 D & E).
Topiramate ameliorates expression of NF-kB and p53
The results of immunohistochemistry of gastric tissue of rats for both NF-kB and p53 proteins also demonstrated a protective effect of topiramate in ethanol induced gastric injury. An increase in expression of NF-kB was observed in the gastric tissue of ethanol treated rats as compared to control animals (Fig. 6 B & A). Pretreatment with topiramate markedly down regulated the over expression of NF-kB (Fig. 6C–E). Similarly immunohistochemistry results for p53 showed an intense staining in the gastric tissue of ethanol treated animals indicative of an over expression of p53 protein when compared with control animals (Fig 7 B – A). Pretreatment with topiramate reduced the expression of p53 protein (Fig 7 C – E).
Effect of Topiramate on ethanol-induced changes in the gastric mucosal myeloperoxidase (MPO)
Pretreatment with topiramate provided a significant protection against ethanol induced gastric injury by reducing the infiltration of activated neutrophils, as seen in the results of the MPO activity in ethanol and topiramate treated animals. Administration of ethanol resulted in a significant increase in MPO activity (P