Ionizing radiations produce deleterious effects in the living organisms and the rapid technological advancement has increased human exposure to ionizing radiations enormously. There is a need to protect humans against such effects of ionizing radiation. Attempts to protect against the deleterious effects of ionizing radiations by pharmacological intervention were made as early as 1949 and efforts are continued to search radioprotectors, which may be of great help for human application. This review mainly dwells on the radioprotective potential of plant and herbal extracts. The results obtained from in vitro and in vivo studies indicate that several botanicals such as Gingko biloba, Centella asiatica, Hippophae rhamnoides, Ocimum sanctum, Panax ginseng, Podophyllum hexandrum, Amaranthus paniculatus, Emblica officinalis, Phyllanthus amarus, Piper longum, Tinospora cordifoila, Mentha arvensis, Mentha piperita, Syzygium cumini, Zingiber officinale, Ageratum conyzoides, Aegle marmelos and Aphanamixis polystachya protect against radiation-induced lethality, lipid peroxidation and DNA damage. The fractionation-guided evaluation may help to develop new radioprotectors of desired activities.
Cancer chemoprevention is fast becoming a lucrative approach for controlling cancer. Carcinogenesis being a complex multi-step, multi-factorial process, a number of chemopreventive interventions can be employed. These strategies are generally directed against two broad events of carcinogenesis viz., initiation and promotion/progression. Anti-initiation interventions principally involve inhibition of carcinogen activation, scavenging of free radicals and reactive carcinogen metabolites along with enhanced detoxification of carcinogens by modulating cellular metabolism. Anti-promotion strategies involve attenuation of enhanced cellular proliferation along with induction of cellular apoptosis and differentiation. Dietary agents or herbal anti-oxidants due to low toxicity and relative safety are promising chemopreventive agents. These agents after emerging successful through a series of in vitro and in vivo assays enter clinical trials. Many dietary compounds have emerged as promising chemopreventive agents in empirical experiments. However, in clinical trials these compounds have met with limited success. This emphasizes the need for further detailed research on the mechanisms of observed chemoprevention and choice, dose, duration and bioavailability of chemopreventive agent used. Complex issues such as choice and nutritional status of target population, genetic variation, gene-environment interactions and relevance of biomarkers analyzed also warrant further research and analyses.
There has been considerable public and scientific interest in the use of phytochemicals derived from dietary components to combat human diseases. They are naturally occurring substances found in plants. Ferulic acid (FA) is a phytochemical commonly found in fruits and vegetables such as tomatoes, sweet corn and rice bran. It arises from metabolism of phenylalanine and tyrosine by Shikimate pathway in plants. It exhibits a wide range of therapeutic effects against various diseases like cancer, diabetes, cardiovascular and neurodegenerative. A wide spectrum of beneficial activity for human health has been advocated for this phenolic compound, at least in part, because of its strong antioxidant activity. FA, a phenolic compound is a strong membrane antioxidant and known to positively affect human health. FA is an effective scavenger of free radicals and it has been approved in certain countries as food additive to prevent lipid peroxidation. It effectively scavenges superoxide anion radical and inhibits the lipid peroxidation. It possesses antioxidant property by virtue of its phenolic hydroxyl group in its structure. The hydroxy and phenoxy groups of FA donate electrons to quench the free radicals. The phenolic radical in turn forms a quinone methide intermediate, which is excreted via the bile. The past few decades have been devoted to intense research on antioxidant property of FA. So, the present review deals with the mechanism of antioxidant property of FA and its possible role in therapeutic usage against various diseases.
Experimental and epidemiological studies have reported that diesel exhaust particles (DEP) can aggravate a variety of respiratory diseases including infection or allergy. However, the responsible components in DEP for the enhancement have not been identified. The present review demonstrates the different effects of the components of DEP on the respiratory diseases related to infection or allergy. We exposed mice to the organic chemicals (DEP-OC) and the residual carbonaceous nuclei (washed DEP) derived from DEP in the presence or absence of bacterial endotoxin (lipopolysaccharide: LPS) or allergen. In our first series of experiments, washed DEP combined with LPS synergistically exacerbated lung injury, which was concomitant with the enhanced lung expression of proinflammatory cytokines and chemokines, whereas DEP-OC combined with LPS did not. In contrast, our second series of experiments showed that DEP-OC, rather than washed DEP, enhanced allergen-related eosinophilic inflammation and proliferation of goblet cells in the airway epithelium, which was paralleled by the enhanced lung expression of eotaxin and interleukin-5. However, washed DEP with ovalbmin showed less change and increased the lung expression of interferon-γ. It is suggested that DEP components diversely affect various types of respiratory diseases, while the combination of organic chemicals and carbonaceous nuclei (whole DEP) mostly aggravate respiratory diseases.
Recently the finding of gastric cancer in Helicobacter pylori (H. pylori)-infected mouse models was reported. Studies of humans and animal models have shown that H. pylori infection stimulates gastric epithelial cell proliferation and apoptosis. Polyphenols contained in green tea and related compounds were reported to have a variety anti-tumor effects and bactericidal properties. We studied the effect of green tea polyphenols on gastric cell proliferation and apoptosis in an H. pylori-infected mouse model. This model was prepared by inoculating Balb/c mice with 108 cfu of H. pylori (NCTC 11637 strain) by gavage. Beginning 18 weeks after inoculation, 0.5% polyphenols were given in drinking water every day for 2 weeks. Mice were sacrificed 1 h after bromodeoxyuridine (BrdU) was given i.p. for preparation of paraffin-embedded specimens. Cell proliferation and apoptosis were examined by the avidin-biotin complex method using anti-BrdU antibody and the TUNEL method, respectively. H. pylori infection resulted in increased BrdU-labeled cells in both the antrum and the bodies. Administration of polyphenols suppressed this increased proliferation. H. pylori infection increased apoptotic cells in both the antrum and the corpus in comparison with controls. This increase was not seen in H. pylori-infected mice given polyphenols. We conclude the administration with polyphenols might suppress gastric carcinogenesis that is in part related to H. pylori infection.
Patients with chronic liver disease (CLD) often develops glucose intolerance. We explored the prevalence of diabetes mellitus in viral CLD, and analyzed factors profoundly affecting the diabetic angiopathies. 229 CLD patients (124 chronic hepatitis and 105 liver cirrhosis) entered the study. The diagnosis of diabetes was made with the criteria by World Health Organization. Laboratory investigation included serum asparate aminotransferase, alanine aminotransferase, albumin, fasting blood sugar, hemoglobin A1c (HbA1c), fasting immunoreactive insulin, and HOMA-R (FBS*IRI/405). The incidence of macro- and microangiopathy were also examined. Forty (17.5%) CLD patients were diagnosed diabetes, giving a significantly higher incidence than that of general cohort (5.3%) (p<0.001). Among them, 12 (30%) had the triopathy, significantly lower than that in a matched group of diabetic patients without CLD (65%) (p<0.001). Significantly increased levels of HbA1c and HOMA-R were observed in diabetic CLD with angiopathy compared with diabetic CLD without. Incidence of diabetes was increased in viral CLD patients. The rate of diabetic angiopathies in CLD, however, was relatively low, this could be explained by low coagulability in these patients. Poor control of hyperglycemia, partly due to insulin resistance, might explain the onset of angiopathy in diabetic CLD.
Leptin-deficient ob/ob mice are a murine model for obesity, insulin resistance, and diabetes. Here we report that non-lethal abdominal irradiation (a single fraction of 850 cGy) to ob/ob mice retarded rapid gain of body weight, leading to amelioration of obesity without marked changes in food intake. This effect was observed only in ob/ob mice and not in lean controls. Reduction of body weight was accompanied by decreased adipose tissue weight without any marked change in the size of adipocytes, indicating prevention of hyperplasia rather than hypertrophy. Gene expression of the radiation-inducible cdk-inhibitor, p21, and the adipocytokines, tumor necrosis factor α and interleukin-1β, were induced as expected; but genes involved in adipogenesis such as peroxisome proliferator-activated receptor γ and adipsin were not affected in the irradiated adipose tissue. Inversely, hepatic lipid content was elevated with concomitant increases in the expression of lipogenic enzymes such as fatty acid synthase (FAS), and sterol regulatory element-binding protein 1c. Despite the decreased adiposity, there was no improvement in hyperglycemia and hyperinsulinemia after the irradiation. In conclusion, abdominal irradiation to ob/ob mice affected the progression of obesity and altered the energy metabolism between organs through a novel mechanism, implicating a new approach or factor for understanding and treatment of obesity.
The protective effect of onion against oxidative stress in streptozotosin-induced diabetic rats was investigated in comparison with that of quercetin aglycone. We measured oxidative stress biomarkers involving the susceptibility of the plasma against copper ion-induced lipid peroxidation, which was estimated by the amounts of thiobarbituric acid-reactive substances (TBARS) and cholesteryl ester hydroperoxides, and urine TBARS and 8-hydroxydeoxyguanosine contents. After the 12-week feeding period, plasma glucose levels and these biomarkers increased in diabetic rats compared to normal rats. In diabetic rats fed a 6.0% onion diet (quercetin equivalent: 0.023%), quercetin metabolites accumulated in the plasma at concentrations of approximately 35 μM. Onion intake decreased plasma glucose levels and lowered the oxidative stress biomarkers. On the other hand, quercetin metabolites in the plasma of rats fed a diet with 0.023% quercetin aglycone were found at lower concentrations (14.2 μM) than the rats fed the onion diet. Furthermore, oxidative stress biomarkers were higher in the quercetin diet group compared to the onion diet group. These results strongly suggest that onion intake suppresses diabetes-induced oxidative stress more effectively than the intake of the same amount of quercetin aglycone alone.
The etiology of essential hypertension includes increased oxidative stress. The role of antihypertensive drug amlodipine as an antioxidant and the benefit of addition of vitamin C, an antioxidant to antihypertensive therapy were studied. Forty male patients of essential hypertension were randomly divided into two groups and treated with 5 mg amlodipine. In addition one group also received 1000 mg vitamin C (as two 500 mg tablets) once daily for three months. Although blood pressure decreased in both groups, the systolic blood pressure in patients given vitamin C was less (126.4 ± 7.47) compared to the other group (130.9 ± 7.27). A decrease in malondialdehyde, an increase in erythrocyte sodium-potassium adenosine triphosphatase (Na+ K+ ATPase) and an increase in the superoxide dismutase levels were observed in both groups. The increase in SOD was statistically more in the patients given vitamin C in addition to amlodipine (0.1717 ± 0.0150 compared to 0.152 ± 0.0219 units/100 ml assay). In spite of the known antihypertensive, antioxidant activity, similarity in correcting endothelial dysfunction independently, giving the two drugs together and early introduction of vitamin C perhaps decreases oxidative stress and augments the antioxidant status. This may prevent further vascular damage due to oxidative stress, leading to a better prognosis in essential hypertension patients.
Nonsteroidal anti-inflammatory drugs (NSAIDs) have gastrointestinal side effects such as dyspepsia, peptic ulcer, hemorrhage, and perforation. Misoprostol and PPIs have been used to prevent NSAID-induced gastroduodenal injury. Rebamipide increases gastric mucus and stimulates the production of endogenous prostaglandins. The prophylactic effect of rebamipide on NSAID-induced gastrointestinal complications is unknown. The aim of this study was to compare NSAID-induced gastrointestinal complications in rebamipide- and misoprostol-treated groups. Patients were randomized to two groups and took a conventional NSAID plus rebamipide or misoprostol for 12 weeks. Gastric mucosal damage was evaluated by endoscopy at screening and the end of the study. The prevalences of active gastric ulcer were 7/176 (3.9%) in the rebamipide group and 3/156 (1.9%) in the misoprostol group. The prevalences of peptic ulcer were 8/176 (4.5%) in the rebamipide group and 7/156 (4.4%) in the misoprostol group. The cumulative incidences of peptic ulcer in the high-risk subgroup were 6/151 (4.0%) for rebamipide and 6/154 (3.9%) for misoprostol. In conclusion, rebamipide prevented NSAID-induced peptic ulcer as effectively as misoprostol in patients on long-term NSAID therapy. Rebamipide may be a useful therapeutic option for the prevention of NSAID-induced gastrointestinal ulcer because of its therapeutic effect and safety.