Effect of myricetin on 1,2 dimethylhydrazine induced rat colon carcinogenesis.

Colorectal cancer (CRC) is a leading cause of cancer mortality especially in the western world. The incidence of CRC in Asia is now increasing at an alarming rate from the previously negligible levels. The pathogenesis of CRC is a multistep process wherein pre cancer lesions accumulate in the mucosal cells finally resulting in cancer. Diet plays an important role in its aetio-pathogenesis--the high levels of dietary fat correlates to the increased incidence of CRC. This along with hereditary, environmental factors and singular lack of physical exercise provides a potent combination in its pathogenesis. Besides CRC isfrequently associated with persistent oxidative stress which results not only in DNA damage but also in mutation of cancer related genes besides the epigenetic silencing of the tumor suppressor gene. An important approach in the prevention of cancer is chemoprevention. Variety of plant products have been found to be highly effective in retarding the pathogenesis of the colorectal cancer. Myricetin is a well known bioflavonoid that is claimed to have anti cancer action particularly in colorectal cancer. Myricetin not only brought about significant decrease in the incidence of number of tumor bearing rats but also the tumor incidence. Myricetin supplementation significantly reduced liver TBARS. Further the anti oxidant enzymes like Catalase, Glutathione peroxidase and GSH were significantly rejuvenated following myricetin supplementation in a dose dependent manner. The fecal and colonic bacterial enzyme activity was also significantly decreased with the supplementation of myricetin 50 and 100 mg/kg. There was no additional benefit with the supplementation of 200 mg/kg of myricetin.

Effect of kaempferol on lipid peroxidation and antioxidant status in 1,2-dimethyl hydrazine induced colorectal carcinoma in rats.

Colorectal cancer, a common cause of cancer related deaths in both sexes in western population is often due to persistent oxidative stress leading to DNA damage. Antioxidants scavenge free radicals and inhibit neoplastic process. Kaempferol, a flavonol widely distributed in tea, broccoli, grape fruit, brussels sprouts and apple, is claimed to have chemopreventive action in colon cancer. The aim of our study was to evaluate the effect of kaempferol on tissue lipid peroxidation and antioxidant status in 1,2-dimethyl hydrazine induced colorectal cancer in male Wistar rats and to compare its efficacy with irinotecan. Experimental colon cancer induced by 1,2-dimethyl hydrazine in rats mimic human colon cancer and therefore is an ideal model for chemoprevention studies. The rats were divided into six groups. Group 1 served as control. Group 2 received 1,2-dimethyl hydrazine (20 mg/kg body weight) subcutaneously once a week for four weeks. Group 3 received irinotecan (100 mg/kg body weight) intravenously once a week for four weeks with 1,2-dimethyl hydrazine. Groups 4 to 6 were given a daily oral dose of 50, 100, 200 mg/kg body weight of kaempferol with 1,2-dimethyl hydrazine. The total study period was 16 weeks. Kaempferol supplementation lowered 1,2-dimethyl hydrazine induced erythrocyte lysate and liver thiobarbituric acid reactive substances level and rejuvenated anti oxidant enzymes catalase, super oxide dismutase and glutathione peroxidase. The recovery of enzyme status was maximum at the dose of 200 mg/kg body weight and was comparable to irinotecan. Our study reveals that kaempferol could be safely used as a chemopreventive agent in colorectal cancer.

Suppression of constitutively expressed cyclooxygenase-2 in the epididymis of mice by nimesulide decreases sperm motility.

Significant levels of constitutive cyclooxygenase-2 (COX-2) are present in the male reproductive organs of rodents, especially in the vas deferens and epididymis. In the epididymis, the sperm storehouse, COX-2 is thought to play a vital role in altering the membrane lipids of sperm. The present study aims at localizing COX-2 in the epididymis and analyzing the effects of the preferential COX-2 inhibitor nimesulide. COX-2 protein activity was nearly equal to that of COX-1 in the cauda epididymis. Immunohistochemical studies showed an intense staining for COX-2 in the cauda epididymis but not in the caput epididymis. Nimesulide administration induced a significant reduction in both COX-2 staining intensity and protein activity, followed by an initial decline in total prostaglandin levels but a reversible increase upon sustained COX-2 suppression. Sperm numbers and vitality showed no significant change, but motility decreased and total and free serum testosterone levels mildly increased.

Localization of cyclooxygenase-2 in mice testis and assessment of its possible role through suppressing its expression using nimesulide: a preferential cyclooxygenase-2 inhibitor.

Present generation non-steroidal anti-inflammatory drugs (NSAID) are potent inhibitors of the enzyme cyclooxygenase-2 (COX-2). Even though they exhibit reduced incidence of gastrotoxicity, severe nephrotoxicity and other side effects have been widely reported with respect to usage of these drugs. Since COX-2 levels are not only upregulated by inflammation but also by other stimuli such as cytokines, growth factors, mitogens and steroid hormones, we investigated the localization of COX-2 and activity of both COX-1 and COX-2 in mice testis. To correlate the localization of COX-2 with its function we suppressed COX-2 expression with the aid of nimesulide a preferential COX-2 inhibitor. We found COX-2 was constitutively expressed in the Leydig cells of mice testis suggesting a role on testosterone synthesis. Suppression of COX-2 resulted in increased concentration of most of polyunsaturated fatty acids especially arachidonic acid (AA). Prostaglandin (PG) levels which showed an initial decline during nimesulide treatment had a reversible effect during prolonged treatment. These findings state that cyclooxygenase is constitutively expressed in mice testis and continuous inhibition of COX-2 interferes in maturation of sperm.

The neuroprotective effect of Withania somnifera root extract in MPTP-intoxicated mice: an analysis of behavioral and biochemical variables.

We studied the influence of Withania somnifera (Ws) root extract (100 mg/kg body weight) on parkinsonism induced by 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP; i.p, 20 mg/kg body weight for 4 days), via the analysis of behavioral features and the oxidant-antioxidant imbalance in the midbrain of mice. A significant alteration in behavior, increased levels of thiobarbituric acid reactive substance (TBARS), and increased activities of superoxide dismutase (SOD) and catalase (CAT) were noticed in this region of brain in MPTP-treated mice. Oral treatment with the root extract resulted in a significant improvement in the mice's behavior and antioxidant status, along with a significant reduction in the level of lipid peroxidation. The results indicated that at least part of the chronic stress-induced pathology may be due to oxidative stress, which is mitigated by Ws. Further studies are needed to assess the precise mechanism to support the clinical use of the plant as an antiparkinsonic drug.

Localization of cyclooxygenase-2 in mice vas deferens and its effects on fertility upon suppression using nimesulide: a preferential cyclooxygenase-2 inhibitor.

Accumulating evidence on constitutive expression of cyclooxygenase-2 (COX-2), one of the isoforms of enzyme cyclooxygenase (COX) the other isoform being cyclooxygenase-1 (COX-1), questions the safety profile of non-steroidal anti-inflammatory drugs (NSAIDs). This COX-2 isoform which is induced not only during inflammation but also by factors such as cytokines, steroid hormones and mitogenic stimuli is constitutively expressed in brain, kidney and reproductive organs. Present NSAIDs, particularly COX-2 inhibitors is no longer considered safe since suppression of COX-2 in tissues which it is constitutively expressed may lead to adverse effects. Though intense expression of COX-2 in vas deferens is proved, lack of information with respect to its function has attracted a wide scope for research as to whether COX-2 in vas deferens contributes to male fertility. In the present study, the authors investigated the localization of COX-2 as well as COX-1 in mice vas deferens and also assessed the activity of COX-2 and total prostaglandin (PG) levels in vas deferens. Further they suppressed the expression of COX-2 using a preferential COX-2 inhibitor nimesulide and analyzed the sperm from vas deferens for any defects. COX-2 was intensely expressed in the epithelial cells of mice vas deferens and nimesulide was able to effectively suppress most of COX-2 expression. A decrease in PG levels was observed initially but interestingly, the levels tend to rise on sustained suppression of COX-2. The motility of sperm was affected severely after 6h of nimesulide administration that suggested a crucial role of COX-2 towards fertility of mice sperm.