The role of nonsteroidal anti-inflammatory drugs (
NSAIDs) was studied on the
antioxidant defense system and
nitric oxide-derived damage in a
1,2-dimethylhydrazine (
DMH)-induced rat colon
carcinogenesis. Early precancerous lesions were established in the proximal and distal regions of the colon by morphological and histopathological examinations that were greatly regressed by the simultaneous treatment of the three
NSAIDs, such as
aspirin,
celecoxib, and
etoricoxib, along with the procarcinogen
DMH. The intestinal brush border membrane (BBM) was isolated from the two regions and the colon-specific marker
enzyme cysteine-sensitive
alkaline phosphatase was assayed, which showed considerable elevation by
DMH but reverted back to normal level by all the three
NSAIDs.
DMH also caused a higher level of lipid peroxidation as measured by
malonyldialdehyde production, which was also found to be corrected by the
NSAIDs, in both the region of the colonic tissue. The
antioxidant activities were further established by a higher level of
superoxide dismutase,
catalase,
glutathione reductase, and
glutathione S-transferase in the
NSAID treatment as compared to the
DMH. The nonenzyme tripeptide,
glutathione content was also recovered similarly as an
antioxidant defense mechanism. To elucidate whether
nitric oxide (NO) also plays an important role in the pathophysiology of
colon cancer, the NO and
citrulline levels were measured. The results show that the NO was lowered in
DMH treatment and elevated by the administration of the
NSAIDs while the
citrulline level could not be recovered back. The findings of the present investigation indicate the chemopreventive modalities of the
NSAIDs, particularly the
COX-2 inhibitors.