Effect of non-steroidal anti-inflammatory drugs and the pro-carcinogen 1,2 dimethylhydrazine on the rat intestinal membrane structure and function.

The present study was designed to evaluate the effects of three non-steroidal anti-inflammatory drugs (NSAIDs) with varying cycloxygenase selectivities on the small intestinal biochemical composition, function and histology during 1, 2-dimethylhydrazine (DMH) administration. Sprague Dawley male rats were divided into five different groups viz: Group 1 (control, vehicle treated), Group 2 (DMH-treated, 30 mg/kg body weight/week in 1 mM EDTA-saline, subcutaneously), Group 3 (DMH + aspirin-60 mg/kg body weight), Group 4 (DMH + celecoxib-6 mg/kg body weight), Group 5 (DMH + etoricoxib-0.64 mg/kg body weight). After six weeks of treatment, brush border membrane was isolated from the jejunum segment of all the groups and changes in the associated enzymes such as sucrase, lactase, maltase, alkaline phosphatase, membrane lipid composition, fluorescence polarizations of diphenylhexatriene, pyrene excimer formation, histological changes and surface characteristics were studied. The results indicated a significant alteration in the enzyme activity as well as changes in the structure and function of the intestine in the presence of the pro-carcinogen, DMH, which suggests the possible chemopreventive efficacy of NSAIDs against the intestinal cancer.

Modulatory effects of N-acetylcysteine on cerebral cortex and cerebellum regions of ageing rat brain.

Oxidative stress has been implicated in brain ageing and in age-related neurodegenerative disorders. Since N-acetylcysteine (NAC) has recently been shown to prevent oxidative damage in ageing brain, we have examined the effects of this thiolic antioxidant on the age associated oxidative stress related parameters in rat brain regions. The lipid peroxide formation, reduced glutathione (GSH) content along with the activities of superoxide dismutase (SOD) and catalase were determined in the cerebral cortex and cerebellum brain regions of the young (4 months) and older (14 months) female rats. The lipid peroxidation was observed to be increased in the cerebral cortex regions accompanied by simultaneous decrease in the GSH content in both the regions of older rats. The SOD activity was reduced in both the regions while catalase was reduced only in cerebellum region of the older rats. Following NAC supplementation (160 mg/kg. b. wt./ day), lipid peroxidation was observed to be reduced which was accompanied by enhanced GSH levels, along with enhanced SOD and catalase in both the brain regions of older age rats. Further, in the younger age rats the NAC treatment resulted in the decrease of lipid peroxidation in both the regions that was accompanied by the increase catalase activity in cerebral cortex region along with increase in GSH content and SOD in cerebellum regions. Our result suggests that the normal brain ageing is associated with the decrease in antioxidative defense status and the supplementation of thiol antioxidants like NAC may prove helpful in managing the age related brain disorders characterized by compromised antioxidative defense systems.

Effects of non steroidal anti-inflammatory drugs on the antioxidant defense system and the membrane functions in the rat intestine.

In the present study the effects of two cycloxygenase-2 (COX-2) selective inhibitors, celecoxib and nimesulide as compared to a non-selective COX inhibitor, aspirin was studied in the rat intestine. Female Wistar rats weighing between 150-175 g were divided into four groups having 8 animals each as follows: Group 1(Control), Group 2- Aspirin (40 mg/kg), Group 3- Nimesulide (10 mg/kg) and Group 4- Celecoxib (10 mg/kg). After 35 days of treatment the animals were sacrificed, intestine removed and the effects on the antioxidant defense system, membrane composition and functions along with the membrane specific enzymes were studied in different regions of the intestine. The study showed a significant increase in the lipid peroxide levels as TBA-reactive substance as well as the conjugated dienes, except for celecoxib treated group which showed a decrease. Significant decrease was also observed in the level of reduced glutathione (GSH), superoxide dismutase (SOD), glutathione-s-transferase and catalase activities for aspirin and nimesulide group while Celecoxib caused an increase in glutathione reductase (GR). Aspirin and nimesulide exhibited an increase in the brush border membrane (BBM) bound enzyme activities like sucrase, lactase, maltase and alkaline phosphatase in the small intestine while celecoxib showed decrease in lactase, maltase and alkaline phosphatase. The phospholipid content increased only for aspirin treated group while cholesterol decreased in all the treatment groups. Also celecoxib treatment brought about an increase in glycolipid content. The membrane fluidity was studied by the rotational diffusion of 1, 6, diphenyl, 1, 3, 5 hexatriene (DPH) incorporated in the membrane and the fluorescence polarization (p), fluorescence anisotropy(r), anisotropy parameter [r0/r-1](-1) and order parameter [S2 = (4/3r - 0.1)/r0] were recorded. No significant change in the fluorescence parameters were observed in the BBM and the liposomes made from the BBM lipids for the treatment groups. These results indicate that celecoxib may be accepted as a safer drug in terms of overall gastro-intestinal toxicity as compared to the aspirin and nimesulide.