In Vitro Anticancer Effects of Cinnamomum verum J. Presl, Cinnamaldehyde, 4 Hydroxycinnamic Acid and Eugenol on an Oral Squamous Cell Carcinoma Cell Line.

AIM AND OBJECTIVE: The present study was conducted to assess the in vitro anticancer effects of Cinnamomum verum J. Presl extract and its active constituents, such as cinnamaldehyde, 4 hydroxycinnamic acid, and eugenol on oral squamous cell carcinoma cell line. MATERIALS AND METHODS: Aqueous, ethanolic, and hydroalcoholic extracts of C. verum J. Presl (bark) were prepared using standardized protocols. Cinnamaldehyde, 4 hydroxycinnamic acid, and eugenol were quantified in the extracts. Total saponins, tannins, and polyphenols were quantified in the selected extracts. A commercially available SCC-25 cell line was cultured according to standard protocol. The anticancer effects of the extract, active compounds, and standard cisplatin were assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cytotoxicity, acridine orange/ethidium bromide staining, DNA, fragmentation assay, cell cycle analysis by flow cytometry, and JC-1 staining (5,5',6,6'-tetrachloro1,1',3,3'tetraethylbenzimidazolylcarbocyanine iodide). RESULTS: The hydroalcoholic extracts demonstrated a higher quantity of the active ingredients cinnamaldehyde, 4 hydroxycinnamic acid, and eugenol. The selected extract and active compounds demonstrated anticancer effects via apoptosis induction and S-phase arrest. Apoptosis induction was exerted by the extract via alteration in mitochondrial membrane potential. CONCLUSION: Cinnamomum verum J. Presl and its active compounds exhibited in vitro anticancer effects on oral squamous cell carcinoma. Further studies in animal models have to be carried out to assess toxicity and in vivo effects. CLINICAL SIGNIFICANCE: The anticancer properties of Cinnamomum verum J. Presl could be explored further for prevention and management of oral squamous cell carcinoma.

Taurine abrogates mammary carcinogenesis through induction of apoptosis in Sprague-Dawley rats.

Breast cancer is one of the most severe problems in oncology. Taurine is a sulfur-containing amino acid with vital biological functions. The current study was intended to investigate the abnormalities in the expression of apoptosis-associated proteins that lead to the progression of 7,12-dimethyl benz[a]anthracene (DMBA)-induced breast cancer and to expose the protective effect of taurine on it. Rats were induced with DMBA by gastric intubation to induce breast cancer. Breast cancer-bearing animals were posttreated with taurine. The breast tumors induced by DMBA, analyzed in the current study, were characterized by increased protein/DNA expression of Bcl-2 associated with downregulation in the expression of p53, Bax, and caspases. Taurine treatment reverted all the above changes induced by DMBA and inhibited the development of rat breast carcinoma through its ability to induce apoptosis.

Modulatory Effect of Taurine on 7,12-Dimethylbenz(a)Anthracene-Induced Alterations in Detoxification Enzyme System, Membrane Bound Enzymes, Glycoprotein Profile and Proliferative Cell Nuclear Antigen in Rat Breast Tissue.

The modulatory effect of taurine on 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer in rats was studied. DMBA (25 mg/kg body weight) was administered to induce breast cancer in rats. Protein carbonyl levels, activities of membrane bound enzymes (Na(+) /K(+) ATPase, Ca(2+) ATPase, and Mg(2+) ATPase), phase I drug metabolizing enzymes (cytochrome P450, cytochrome b5, NADPH cytochrome c reductase), phase II drug metabolizing enzymes (glutathione-S-transferase and UDP-glucuronyl transferase), glycoprotein levels, and proliferative cell nuclear antigen (PCNA) were studied. DMBA-induced breast tumor bearing rats showed abnormal alterations in the levels of protein carbonyls, activities of membrane bound enzymes, drug metabolizing enzymes, glycoprotein levels, and PCNA protein expression levels. Taurine treatment (100 mg/kg body weight) appreciably counteracted all the above changes induced by DMBA. Histological examination of breast tissue further supported our biochemical findings. The results of the present study clearly demonstrated the chemotherapeutic effect of taurine in DMBA-induced breast cancer.

Cytoprotective role of astaxanthin against glycated protein/iron chelate-induced toxicity in human umbilical vein endothelial cells.

Astaxanthin (ASX), a red carotenoid pigment with no pro-vitamin A activity, is a biological antioxidant that occurs naturally in a wide variety of plants, algae and seafoods. This study investigated whether ASX could inhibit glycated protein/iron chelate-induced toxicity in human umbilical-vein endothelial cells (HUVEC) by interfering with ROS generation in these cells. Glycated fetal bovine serum (GFBS) was prepared by incubating fetal bovine serum (FBS) with high-concentration glucose. Stimulation of cultured HUVECs with 50 mm 1 mL of GFBS significantly enhanced lipid peroxidation and decreased antioxidant enzyme activities and levels of phase II enzymes. However, preincubation of the cultures with ASX resulted in a marked decrease in the level of lipid peroxide (LPO) and an increase in the levels of antioxidant enzymes in an ASX concentration-dependent manner. These results demonstrate that ASX could inhibit LPO formation and enhance the antioxidant enzyme status in GFBS/iron chelate-exposed endothelial cells by suppressing ROS generation, thereby limiting the effects of the AGE-RAGE interaction. The results indicate that ASX could have a beneficial role against glycated protein/iron chelate-induced toxicity by preventing lipid and protein oxidation and increasing the activity of antioxidant enzymes.

In vivo protective effect of crocetin on benzo(a)pyrene-induced lung cancer in Swiss albino mice.

The objective of this investigation was to determine the efficacy of crocetin in preventing lung tumorigenesis in mice. We evaluated crocetin in Swiss albino mice treated with the tobacco-specific carcinogen benzo(a)pyrene [B(a)P] for their ability to inhibit pulmonary adenoma formation and growth. Male Swiss albino mice (7 weeks old) were given 100 mg/kg B(a)P by i.p. injection, and 4 or 14 weeks later, they were given crocetin 50 mg/kg by i.p. injection 3 days/week. Crocetin (50 mg/kg body weight) reduced proliferating cells by 68% and 45% in 18 and 8 weeks of treatment respectively. The levels of glycoproteins and polyamines were significantly altered in the B(a)P-induced animals than in crocetin treatment groups. The activity of crocetin was more pronounced in the cancer. Taken together, these results indicate that crocetin was capable of inhibiting proliferation cells by inhibiting proliferating cells, glycoprotein and polyamine synthesis.

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.

Therapeutic effect of paclitaxel and propolis on lipid peroxidation and antioxidant system in 7,12 dimethyl benz(a)anthracene-induced breast cancer in female Sprague Dawley rats.

Breast cancer is one of the most common cancers in women of developed and developing countries. The optimum management of which requires a multidisciplinary approach including the use of certain biochemical and molecular markers. The effect of propolis along with paclitaxel on 7,12 dimethyl benz(a)anthracene (DMBA) induced experimental breast cancer was investigated in female Sprague Dawley rats. Female Sprague Dawley rats were divided into five groups of six animals each. Group I served as normal control animal. Group II animals received DMBA (20 mg in 0.5 ml sunflower oil and 0.5 ml of saline) i.p. to develop mammary tumor by the end of 90 days. Group III were breast cancer animals treated with 33 mg paclitaxel/kg body weight (bw) weekly once for 4 weeks. Group IV were breast cancer-bearing animals treated with 50 mg propolis/kg bw for 30 days. Group V were breast cancer-bearing animals treated with both paclitaxel and propolis as mentioned above. Administration of paclitaxel and propolis effectively suppressed breast cancer, which is revealed by the decrease in the extent of lipid peroxidation (LPO) with concomitant increase in the activities of enzymic antioxidants (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)) and non-enzymic antioxidants (reduced glutathione (GSH), Vitamin C and Vitamin E) levels when compared to breast cancer-bearing animals treated with either paclitaxel or propolis alone. From our results, we conclude that propolis is a potent antioxidant and, when given in combination with paclitaxel, offers maximum protection against DMBA induced mammary carcinogenesis.

Enhancement of antitumor effect of paclitaxel in combination with immunomodulatory Withania somnifera on benzo(a)pyrene induced experimental lung cancer.

The current experimental work deals with the immunomodulatory studies on the extract of Withania somnifera (L.) Dunal root powder against benzo(a)pyrene induced lung cancer in male Swiss albino mice. In our previous study, we reported the antioxidant and anticarcinogenic effect of W. somnifera (L.) Dunal along with paclitaxel. Immune dysfunction has been found to be associated with cancer and chemotherapy. Benzo(a)pyrene induced cancer animals were treated with 400mg/kg bodyweight of W. somnifera (L.) Dunal extract for 30 days significantly alters the levels of immunocompetent cells, immune complexes and immunoglobulins. Based on the data, the carcinogen as well as the paclitaxel affects the immune system, the toxic side effects on the immune system is more reversible and more controllable by W. somnifera (L.) Dunal. These results concluded the immunomodulatory activity of W. somnifera (L.) Dunal extract, which is a known immunomodulator in indigenous medicine.

Cellular metabolic energy modulation by tangeretin in 7,12-dimethylbenz(a) anthracene-induced breast cancer.

Breast cancer is the leading cause of death among women worldwide. Chemoprevention and chemotherapy play beneficial roles in reducing the incidence and mortality of cancer. Epidemiological and experimental studies showed that naturally-occurring antioxidants present in the diet may act as anticancer agents. Identifying the abnormalities of cellular energy metabolism facilitates early detection and management of breast cancer. The present study evaluated the effect of tangeretin on cellular metabolic energy fluxes in 7,12-dimethylbenz(a) anthracene (DMBA)-induced proliferative breast cancer. The results showed that the activities of glycolytic enzymes significantly increased in mammary tissues of DMBA-induced breast cancer bearing rats. The gluconeogenic tricarboxylic acid (TCA) cycle and respiratory chain enzyme activities significantly decreased in breast cancer-bearing rats. In addition, proliferating cell nuclear antigen (PCNA) was highly expressed in breast cancer tissues. However, the activities of glycolytic enzymes were significantly normalized in the tangeretin pre- and post-treated rats and the TCA cycle and respiratory chain enzyme activities were significantly increased in tangeretin treated rats. Furthermore, tangeretin down-regulated PCNA expression on breast cancer-bearing rats. Our study demonstrates that tangeretin specifically regulates cellular metabolic energy fluxes in DMBA-induced breast cancer-bearing rats.

Role of human organic anion transporter 4 in the transport of ochratoxin A.

The purpose of this study was to investigate the characteristics of ochratoxin A (OTA) transport by multispecific human organic anion transporter 4 (hOAT4) using mouse proximal tubule cells stably transfected with hOAT4 (S(2) hOAT4). Immunohistochemical analysis revealed that hOAT4 protein was localized to the apical side of the proximal tubule. S(2) hOAT4 expressed hOAT4 protein in the apical side as well as basolateral side and the cells were cultured on the plastic dish for experiments. S(2) hOAT4 exhibited a time- and concentration-dependent, and a saturable increase in OTA uptake, with an apparent K(m) value of 22.9+/-2.44 microM. The OTA uptakes were inhibited by several substrates for the OATs. Probenecid, piroxicam, octanoate and citrinin inhibited OTA uptake by hOAT4 in a competitive manner (K(i)=44.4-336.4 microM), with the following order of potency: probenecid > piroxicam > octanoate >citrinin. The efflux of OTA by S(2) hOAT4 was higher than that by mock. Addition of OTA resulted in slight decrease in viability of S(2) hOAT4 compared with mock. These results indicate that hOAT4 mediates the high-affinity transport of OTA on the apical side of the proximal tubule, whereas the transport characteristics of OTA are distinct from those by basolateral OATs.

Antitumor efficacy of tangeretin by targeting the oxidative stress mediated on 7,12-dimethylbenz(a) anthracene-induced proliferative breast cancer in Sprague-Dawley rats.

PURPOSE: The aim of the present study was to assess the chemopreventive and chemotherapeutic efficacy of tangeretin on DMBA-induced oxidative stress in breast cancer-bearing Sprague-Dawley rats. METHODS: In this study, the experimental animals were divided into five groups of six animals each. Group I was control, Group II was DMBA-induced breast cancer-bearing rats, Group III was tangeretin pre-treated (50 mg/kg body weight for 30 days orally) breast cancer-bearing animals, Group IV was tangeretin post-treated (50 mg/kg body weight for 30 days orally) and Group V was tangeretin (50 mg/kg body weight) alone treated animals. RESULTS: We have observed the general characteristics of cancer, oxidative stress markers, breast cancer marker, antioxidants and histopathological changes in the experimental animals. We have recorded the body weight, tumor weights, tumor volume and antitumor activity of tangeretin in the experimental animals. Oxidative stress markers, like NO and LPO, and breast cancer marker CEA levels were significantly (p < 0.001, p < 0.05) increased as well as the antioxidants like SOD, CAT, GPx, GST, GSH, ascorbic acid and α-tocopherol were found to be significantly (p < 0.05) decreased in cancer-bearing Group II animals. Whereas, the enzymic and non-enzymic antioxidant levels were found to be significantly decreased in cancer-bearing animals. However, in tangeretin pre-treated and post- treated animals, the levels of antioxidants and breast cancer marker were found to be significantly (p < 0.05) reduced with a concomitant increase in the activities of the antioxidants (p < 0.05). In tangeretin alone treated Group V animals, no significant changes were observed in the levels of antioxidants and breast cancer marker. These results were adequately supported by the histopathological studies in the mammary tissues of the experimental animals. CONCLUSION: From this study, we conclude that the administration of tangeretin was found to be beneficial against DMBA-induced oxidative stress in breast cancer-bearing animals. Hence, we strongly suggest that tangeretin is effective and efficient candidate for the treatment of experimental breast cancer.

Taurine Regulates Mitochondrial Function During 7,12-Dimethyl Benz[a]anthracene Induced Experimental Mammary Carcinogenesis.

OBJECTIVES: The present study was undertaken to determine the modulatory effect of taurine on the liver mitochondrial enzyme system with reference to mitochondrial lipid peroxidation (LPO), antioxidants, major tricarboxylic acid cycle enzymes, and electron transport chain enzymes during 7,12-dimethyl benz[a]anthracene (DMBA) induced breast cancer in Sprague-Dawley rats. METHODS: Animals in which breast cancer had been induced by using DMBA (25 mg/kg body weight) showed an increase in mitochondrial LPO together with decreases in enzymic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST)), non-enzymic antioxidants (reduced glutathione (GSH), vitamin C, and vitamin E), in citric acid cycle enzymes (isocitrate dehydrogenase (ICDH), alpha ketoglutarate dehydrogenase (alpha KDH), succinate dehydrogenase (SDH) and malate dehydrogenase (MDH)), and in electron transport chain (ETC) complexes. RESULTS: Taurine (100 mg/kg body weight) treatment decreased liver mitochondrial LPO and augmented the activities/levels of enzymic, and non-enzymic antioxidants, tricarboxylic acid cycle enzymes and ETC complexes. CONCLUSION: The results of our present study demonstrated the chemotherapeutic efficacy of taurine treatment for DMBA-induced breast carcinomas.

Protective effect of piperine on benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice.

BACKGROUND: The statistics on lung cancer necessitates the urge to develop new methods to control this most deadly form of cancer. Chemoprevention is one of these new approaches. Carcinogens from cigarette smoke form the link between nicotine addiction and lung cancer. At the same time, it has become increasingly clear that dietary and genetically determined factors play an important role in modulating the individual susceptibility and are linked to the chemoprevention approach. In this study, the ability of piperine to prevent lung carcinogenesis in mice was characterized and its effects on cell proliferation and protein damage biomarkers were determined. METHODS: Thirty Swiss albino mice were divided into five groups of six animals each. Animals in group I received corn oil orally and served as control. Group II were administered with 50 mg/kg b.wt. of benzo(a)pyrene (B(a)P) twice a week for 4 consecutive weeks to induce lung cancer by the end of 16th week. Group III received 50 mg/kg b.wt. piperine on alternate days for 16 weeks immediately after the first dose of carcinogen. Group IV also received piperine as in group III but from the sixth week of B(a)P induction till the end of the experiment. Group V animals constituted the drug control and received piperine alone. RESULTS: Administration of piperine significantly decreased the levels of lipid peroxidation, protein carbonyls, nucleic acid content and polyamine synthesis that were found to be increased in lung cancer bearing animals. CONCLUSIONS: Piperine could effectively inhibit B(a)P-induced lung carcinogenesis in albino mice by offering protection from protein damage and also by suppressing cell proliferation.

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.

The vascular endothelium and human diseases.

Alterations of endothelial cells and the vasculature play a central role in the pathogenesis of a broad spectrum of the most dreadful of human diseases, as endothelial cells have the key function of participating in the maintenance of patent and functional capillaries. The endothelium is directly involved in peripheral vascular disease, stroke, heart disease, diabetes, insulin resistance, chronic kidney failure, tumor growth, metastasis, venous thrombosis, and severe viral infectious diseases. Dysfunction of the vascular endothelium is thus a hallmark of human diseases. In this review the main endothelial abnormalities found in various human diseases such as cancer, diabetes mellitus, atherosclerosis, and viral infections are addressed.

Resveratrol interferes with N-nitrosodiethylamine-induced hepatocellular carcinoma at early and advanced stages in male Wistar rats.

Resveratrol, a phytochemical compound abundant in red wine and grapes, is known to affect cancer cells both in vitro and in vivo. A great amount of data have indicated the therapeutic benefits of resveratrol against cancer. However, it remains unclear whether these benefits are similar and equally effective in both the early and advanced stages of cancer or carcinogenesis. In this study, we report the effects of resveratrol in the early and advanced stages of hepatocarcinogenesis in a model of N-nitrosodiethylamine (DEN)-induced hepatocellular carcinoma (HCC) of male Wistar rats. For the experiment, rats were divided into different groups and treated with resveratrol either from day 1 of DEN administration for 15 days (pre-HCC), or after the development of HCC, i.e., 15-16 weeks after DEN administration (post-HCC), and compared to untreated HCC-bearing rats. Biochemical analysis of α-fetoprotein, the known serum marker for HCC, and other serum and liver marker enzymes also demonstrated a decreased level upon resveratrol treatment compared to the untreated HCC-bearing rats. H&E staining of tissue sections from the liver showed alteration or transformation of liver parenchymatous tissue in DEN-induced HCC (at 15-16 weeks). Resveratrol treatment during early (on day 1 of DEN-induction) and advanced (weeks 17-18) HCC showed a marked difference in the tissue architecture compared to untreated HCC. Immunoblot analysis revealed that resveratrol intervention at both the early and advanced stages of DEN-induced HCC activated the apoptotic markers, such as PARP cleavage, caspase-3 activation, p53 up-regulation and cytochrome-c release. In addition, semiquantitative RT-PCR and immunoblot analysis demonstrated the up- and down-regulation of key apoptotic regulators, such as Bax and Bcl2, respectively, in a resveratrol treatment-dependent manner. Our results indicate that the administration of resveratrol either at the early or advanced stages of hepatocarcinogenesis is equally effective and involves the activation of the apoptotic pathway in male Wistar rats.

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.

Ursolic acid attenuates oxidative stress-mediated hepatocellular carcinoma induction by diethylnitrosamine in male Wistar rats.

Hepatocellular carcinoma is the most common primary cancer of the liver in Asian countries. For more than a decade natural dietary agents including fruits, vegetables and spices have drawn a great deal of attention in the prevention of diseases, preferably cancer. Ursolic acid is a natural triterpenoid widely found in food, medicinal herbs, apple peel and other products it has been extensively studied for its anticancer and antioxidant properties. The purpose of this study was to evaluate the effect of ursolic acid in diethylnitrosamine (DEN) induced and phenobarbital promoted hepatocarcinogenesis in male Wistar rats. Antioxidant status was assessed by alterations in level of lipid peroxides and protein carbonyls. Damage to plasma membranes was assessed by levels of membrane and tissue ATPases. Liver tissue was homogenized and utilized for estimation of lipid peroxides, protein carbonyls and glycoproteins. Anticoagulated blood was utilized for erythrocyte membrane isolation. Oral administration of UA 20 mg/kg bodyweight for 6 weeks decreased the levels of lipid peroxides and protein carbonyls at a significance of p< 0.05. Activities of membrane and tissue ATPases returned to normal after UA administration. Levels of glycoproteins were also restored after treatment. Histopathological observations were recorded. The findings from the above study suggest the effectiveness of UA in reducing the oxidative stress mediated changes in liver of rats. Since UA has been found to be a potent antioxidant, it can be suggested as an excellent chemopreventive agent in overcoming diseases like cancer which are mediated by free radicals.