Potent chemopreventive effect of mangiferin on lung carcinogenesis in experimental Swiss albino mice.

AIM OF THE STUDY: In the present study the effects of mangiferin were tested against lung cancer-bearing mice in both the pre-initiation and post-initiation periods. MATERIALS AND METHODS: Healthy male Swiss albino mice (6-8 weeks old) were used throughout the study. The animals were treated with mangiferin (100 mg/kg body weight dissolved in corn oil) two weeks before (pre-initiation) and the twelfth week after (post-initiation) the establishment of B (a) P (50 mg/kg body weight)-induced lung carcinoma. RESULTS: The body weight decreased and the lung weight and levels of xenobiotic and liver marker enzymes markedly increased in the carcinogen-administered animals; and mangiferin treatment brought the values of these parameters back to the near-normal ones. The activities of lysosomal enzymes in the animals with B (a) P-induced experimental lung carcinogenesis were also assessed. In these animals there was an increase in the activities of lysosomal enzymes such as acidphosphatase, ß-glucuronidase, N-acetyl glucosaminidase, and ß-galactosidase. CONCLUSION: Supplementation with mangiferin attenuated all these alterations, thus indicating its anticancer effect. Overall, the above data showed that the anticancer effect of mangiferin as a chemopreventive agent was pronounced.

Immunomodulatory Effect of Mangiferin in Experimental Animals with Benzo(a)Pyrene-induced Lung Carcinogenesis.

The immunomodulatory activity of mangiferin was studied in various groups of animals. For this study, adult Swiss albino male mice were treated with benzo(a)pyrene, abbreviated as B(a)P, at 50 mg/kg body weight orally twice a week for 4 weeks; and mangiferin was also given orally (pre- and post-initiation of carcinoma) at 100 mg/kg body weight. Immunocompetence and immune complexes as measured by phagocyte index, avidity index, and soluble immune complex (SIC) levels (p<0.001), as well as NBT reduction, were decreased in the B(a)P-treated animals;whereas increased levels of immunocompetence were noted in the mangiferin-treated animals given B(a)P (p<0.001, p<0.05). The levels of immunoglobulins such as IgG and IgM were decreased considerably (p<0.001) in the B(a)P-treated animals compared with their levels in the control animals; whereas the IgA level was increased (p<0.001). In the mangiferin-treated experimental animals given B(a)P, the levels of IgG and IgM were significantly (p<0.001, p<0.05) increased whereas the IgA level was decreased compared with those for the B(a)P-treated mice. Oxidative changes in lymphocytes, neutrophils, and macrophages were also measured. The enhanced lipid peroxidation and decreased catalase and superoxide dismutase activities found in the lymphocytes, polymorphonuclear cells (PMN), and macrophages from B(a)P-treated mice were significantly reduced and increased, respectively, by the mangiferin treatment. This study confirms the immunomodulatory effect of mangiferin and shows an immunoprotective role arbitrated through a reduction in the reactive intermediate-induced oxidative stress in lymphocytes, neutrophils, and macrophages.

Effect of fresh apple extract on glycated protein/iron chelate-induced toxicity in human umbilical vein endothelial cells in vitro.

Consumption of fruits and vegetables has been associated with a low incidence of cardiovascular and other chronic diseases. The present study was aimed at evaluating the protective effects of fresh apple extract (AE) on human umbilical vein endothelial cells (HUVEC) exposed to cytotoxic glycated protein (GFBS)/iron (FeCl(3)) chelate. The experimental design comprised 10 groups with 5 flasks in each group. Group I was treated with 15% foetal bovine serum (FBS). Groups II, III and IV were treated with GFBS (70 microM), FBS + FeCl(3) (20 microM), and GFBS + FeCl(3), respectively. The other six groups were as follows: Group V, GFBS + AE (100 microg); Group VI, FBS + FeCl(3) + AE (100 microg); Group VII, GFBS + FeCl(3) + AE (100 microg); Group VIII, GFBS + AE (250 microg); Group IX, FBS + FeCl(3) + AE (250 microg); and Group X, GFBS + FeCl(3) + AE (250 microg). After 24 h incubation, cells were collected from all the experimental groups and assessed for lipid peroxidation (LPO) and activities of the antioxidant enzymes cytochrome c reductase and glutathione S-transferase (GST). HUVEC incubated with glycated protein (GFBS) either alone or combined with iron chelate showed a significant (p < 0.001) elevation of LPO accompanied by depletion of superoxide dismutase, catalase, glutathione peroxidase (GPx) and glutathione reductase (GR), in addition to increased microsomal cytochrome c reductase and decreased GST activities. Treatment of GFBS- or GFBS + FeCl(3)-exposed HUVEC with AE at 100 or 250 microg significantly decreased the level of LPO and returned the levels of antioxidants cytochrome c reductase and GST to near normal in a dose-dependent manner. The extracts recovered viability of HUVEC damaged by GFBS-iron treatment in a concentration-dependent manner. These findings suggest a protective effect of AE on HUVEC against glycated protein/iron chelate-induced toxicity, which suggests that AE could exert a beneficial effect by preventing diabetic angiopathies.

Naringenin reduces tumor size and weight lost in N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric carcinogenesis in rats.

Carcinoma of the stomach is reportedly the second most common cancerous condition affecting the general population. Administration of antioxidants is reported to effectively alleviate the risk of gastric carcinoma. Therefore, we assessed the protective role of naringenin, an antioxidant and naturally occurring citrus flavanone, on gastric carcinogenesis induced by MNNG (200 mg/kg body weight) and S-NaCl (1 mL per rat) in Wistar rats (obtained from the Central Animal House Facility, University of Madras, Taramani Campus, Chennai, India). The animals were divided into 5 groups, and the effects of naringenin on simultaneous and posttreated stages of MNNG were tested. Cancer risk was analyzed along with their antioxidant status. The LPO levels in the experimental groups were assessed as an index of oxidative milieu. Altered redox status was subsequently investigated by assaying the superoxide and hydroxyl radicals, the enzymatic antioxidants (SOD, CAT, GPx), and the nonenzymatic antioxidants viz reduced GSH, vitamin C, and vitamin E. In the presence of MNNG, cancer incidence and LPO levels were significantly increased, whereas enzymatic (SOD, CAT, and GPx) and nonenzymatic antioxidant activities (GSH, Vitamins C, and E) were decreased in the treated rats compared with control rats. Administration of naringenin to gastric carcinoma-induced rats largely up-regulated the redox status to decrease the risk of cancer. We conclude that up-regulation of antioxidants by naringenin treatment might be responsible for the anticancer effect in gastric carcinoma.

Impact of naringenin on glycoprotein levels in N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric carcinogenesis in rats.

We have studied the chemopreventive role of naringenin against experimental gastric carcinogenesis in male Wistar rats. The animals were divided into five groups and six animals were included in each group. Stomach, liver, sera and kidney specimens were collected in the 20th week and the level of glycoproteins namely, hexose, hexosamine, sialic acid and fucose, were measured in the control, gastric cancer-induced, cancer naringenin pretreated, cancer naringenin posttreated and naringenin alone animals. The glycoprotein levels were increased in the gastric cancer-induced rats when compared with the control rats. The levels of glycoprotein were decreased significantly in cancer-bearing rats supplemented with naringenin as compared with the gastric cancer-induced rats. The result shows the gastroprotective effect of naringenin and describes the likelihood of naringenin in maintaining the integrity of cell membranes and gastric mucosa against oxidative damage. Moreover, we hypothesize that regulation of glycoprotein levels by naringenin could be associated with the regression of N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric carcinoma.

Cytoprotective effect of mangiferin on benzo(a)pyrene-induced lung carcinogenesis in swiss albino mice.

Antioxidants are one of the key players in tumourigenesis, and several natural and synthetic antioxidants have been shown to have anticancer effects. In the present investigation, the efficacy of mangiferin on the antioxidant status of benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice was assessed. The animals were divided into five groups. The animals in groups I and V were normal control and mangiferin control, respectively. Groups II, III and IV were administered with benzo(a)pyrene (50 mg/kg body weight, orally) for 4 weeks (twice a week) to induced lung carcinogenesis. Starting 1 week prior to benzo(a)pyrene administration, group III animals were treated with mangiferin (100 mg/kg body weight) in the diet for 18 weeks; 12 weeks after benzo(a)pyrene administration, group III animals were treated with mangiferin that continued until the end of the experiment period (18 weeks). At the end of the experiment period, the reactive oxygen species, glutathione and the activities of antioxidant enzymes were assessed in both lung and liver tissues. The levels of glutathione, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, vitamin E and vitamin C were decreased in group II animals. However, in the mangiferin + benzo(a)pyrene-treated groups III and IV, the levels of GSH and the activities of antioxidant enzymes in both lung and liver were improved when compared with benzo(a)pyrene-induced group II animals. In addition, the finding that mangiferin decreased reactive oxygen species levels and enhanced antioxidant status suggests that this polyphenol might also be of value in the prevention of benzo(a)pyrene-induced lung carcinogenesis.

Protective role of mangiferin against Benzo(a)pyrene induced lung carcinogenesis in experimental animals.

In recent years, considerable emphasis has been focused on identifying new chemopreventive agents which could be useful for the human population. In the present study, we examined the protective role of mangiferin during experimental lung carcinogenesis with reference to its effect on DNA-damage and the detoxification enzyme system. The activities of detoxifying enzymes such as glutathione transferase (GST), quinone reductase (QR) and uridin 5'-diphosphate-glucuronosyl transferase (UDP-GT) were found to be decreased while the lipid peroxidation level was increased in the lung cancer bearing animals. Supplementation of mangiferin (100 mg/kg b.wt) enhanced the detoxification enzymes and reduced DNA damage as determined by single cell electrophoresis. Furthermore, the DNA-protein cross links which was found to be high in lung cancer bearing animals was also modulated upon supplementation with mangiferin. Our present results explain the unique association between the anti-oxidant effect of mangiferin and ultimately the capability of mangiferin to prevent cancer.

Chemopreventive efficacy of mangiferin against benzo(a)pyrene induced lung carcinogenesis in experimental animals.

Chemoprevention has emerged as a very effective preventive measure against carcinogenesis. Several bioactive compounds present in fruits and vegetables have revealed their cancer curative potential on carcinogenesis. Tumor markers correlate strongly with prognosis on tumor burden. Glycoprotein and membrane ATPases play an important role in carcinogenesis. Hence this study was launched to evaluate the effect of mangiferin on the changes in glycoprotein components, ATPases and membrane lipid peroxidation in control and lung carcinoma bearing mice. A significant increase in the levels of glycoproteins, membrane ATPases and membrane lipid peroxidation were observed in animals with lung carcinoma. On administration of mangiferin, these changes were reverted back to near normal levels. The increased levels of glycoprotein components found in lung carcinoma were also significantly decreased in mangiferin treated. Overall, the above data shows that the anticancer effect of mangiferin is more pronounced when used as an chemopreventive agent rather than as a chemotherapeutic agent against B(a)P induced lung carcinogenesis.

Antitumour activity of crocetin in accordance to tumor incidence, antioxidant status, drug metabolizing enzymes and histopathological studies.

Lung cancer is the leading cause of cancer related mortality worldwide. Crocetin, saffron plant derivative known to play a role in cancer chemoprevention. In the present study the effects of crocetin was tested against lung cancer-bearing mice in both pre-initiation and post-initiation periods. Healthy male Swiss albino mice (6-8 weeks old) were used throughout the study. Experiment was designed with the treatment regimen of crocetin [20 mg/kg body weight dissolved in dimethyl sulphoxide (DMSO)] for 4 weeks before (pre-initiation) and from 12th week after Benzo(a) pyrene B(a)p (50 mg/kg body weight) induced lung carcinoma(post-initiation). The level of lipid peroxidation (LPO) and marker enzymes markedly increased in carcinogen administered animals, which was brought back to near normal by crocetin treatment. The activities of the enzymic antioxidants and glutathione metabolizing enzymes were decreased in B(a)p induced animals and increased upon drug treatment. Crocetin profoundly reverted back the pathological changes observed in cancerous animals. From the results crocetin proves to scavenge free radical and plays an important role in cellular function. Tumor incidence and histopathological studies proves crocetin is a potent antitumour agent.