Carmia Borek

Antioxidant Health Effects of Aged Garlic Extract

Oxidative modification of DNA, proteins and lipids by reactive oxygen species (ROS) plays a role in aging and disease, including cardiovascular, neurodegenerative and inflammatory diseases and cancer. Extracts of fresh garlic that are aged over a prolonged period to produce aged garlic extract (AGE) contain antioxidant phytochemicals that prevent oxidant damage. These include unique water-soluble organosulfur compounds, lipid-soluble organosulfur components and flavonoids, notably allixin and selenium. Long-term extraction of garlic (up to 20 mo) ages the extract, creating antioxidant properties by modifying unstable molecules with antioxidant activity, such as allicin, and increasing stable and highly bioavailable water-soluble organosulfur compounds, such as S-allylcysteine and S-allylmercaptocysteine. AGE exerts antioxidant action by scavenging ROS, enhancing the cellular antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase, and increasing glutathione in the cells. AGE inhibits lipid peroxidation, reducing ischemic/reperfusion damage and inhibiting oxidative modification of LDL, thus protecting endothelial cells from the injury by the oxidized molecules, which contributes to atherosclerosis. AGE inhibits the activation of the oxidant-induced transcription factor, nuclear factor (NF)-kappa B, which has clinical significance in human immunodeficiency virus gene expression and atherogenesis. AGE protects DNA against free radical--mediated damage and mutations, inhibits multistep carcinogenesis and defends against ionizing radiation and UV-induced damage, including protection against some forms of UV-induced immunosuppression. AGE may have a role in protecting against loss of brain function in aging and possess other antiaging effects, as suggested by its ability to increase cognitive functions, memory and longevity in a senescence-accelerated mouse model. AGE has been shown to protect against the cardiotoxic effects of doxorubicin, an antineoplastic agent used in cancer therapy and against liver toxicity caused by carbon tetrachloride (an industrial chemical) and acetaminophen, an analgesic. Substantial experimental evidence shows the ability of AGE to protect against oxidant-induced disease, acute damage from aging, radiation and chemical exposure, and long-term toxic damage. Although additional observations are warranted in humans, compelling evidence supports the beneficial health effects attributed to AGE, i.e., reducing the risk of cardiovascular disease, stroke, cancer and aging, including the oxidant-mediated brain cell damage that is implicated in Alzheimers disease.

Lycium barbarum (goji) juice improves in vivo antioxidant biomarkers in serum of healthy adults.

Although Lycium barbarum (goji) and active compounds, Lycium barbarum polysaccharides (LBP), have a high in vitro antioxidant score as determined by simple chemical reaction methods, their in vivo antioxidant effects in humans have not been extensively examined. After our earlier report that an LBP-standardized Lycium barbarum preparation (GoChi) helps prevent oxidant stress-related conditions in humans, our present study examined the hypothesis that the antioxidant effects of GoChi result from its ability to enhance endogenous antioxidant factors. We investigated the effects of GoChi in a 30-day randomized, double-blind, placebo-controlled clinical study. The study population included 50 Chinese healthy adults aged 55 to 72 years. In vivo antioxidant markers, consisting of serum levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and lipid peroxidation (indicated by decreased levels of malondialdehyde, MDA) were examined preintervention and postintervention with GoChi or placebo (120 mL/d). In the GoChi group, antioxidant markers significantly increased by 8.4% for SOD and 9.9% for GSH-Px between the preintervention and postintervention measurements, whereas MDA were significantly decreased by 8.7%. In addition, the SOD, GSH-Px, and MDA levels in the GoChi group were significantly different from those in the placebo group at the postintervention time point, with increases of 8.1% and 9.0% and a decrease of 6.0%, respectively. No significant differences were detected between the preintervention and postintervention time points in the placebo group. These results indicate that GoChi increased antioxidant efficacies in humans by stimulating endogenous factors and suggest that continued use beyond 30 days might help prevent or reduce free radical-related conditions.

Toxicity and biochemical mechanisms of ozone

Ozone is a reactive environmental oxidant molecule whose deleterious effects are enhanced by interaction with other photochemical oxidants. While the pulmonary system is the primary target for ozone toxicity, at a morphological and biochemical level, extrapulmonary toxic effects are well documented. The consequences of exposure to ozone depend on its concentration and are influenced by genetic and host factors. Ozone damage is in part mediated via free radicals formed in the processes of direct peroxidation of polyunsaturated fatty acids by ozone and oxidation of proteins, amines, and thiols. Antidoxidants such as Vitamin E which scavenge the chain-propagating free radicals and stop antioxidation serve as protectors in ozone-induced toxicity.

Garlic Reduces Dementia and Heart-Disease Risk

Risk factors for cardiovascular disease, including high cholesterol, high homocysteine, hypertension and inflammation, increase the risk of dementia, including its most common form, Alzheimers disease (AD). High cholesterol is also associated with elevated beta-amyloid (Abeta), the hallmark of AD. Oxidative damage is a major factor in cardiovascular disease and dementia, diseases whose risk increases with age. Garlic, extracted and aged to form antioxidant-rich aged garlic extract (AGE or Kyolic), may help reduce the risk of these diseases. AGE scavenges oxidants, increases superoxide dismutase, catalase, glutathione peroxidase, and glutathione levels, and inhibits lipid peroxidation and inflammatory prostaglandins. AGE reduces cholesterol synthesis by inhibiting 3-hydroxy-3-methylglutaryl-CoA reductase and is additive with statins in its action. Inhibition of cholesterol, LDL oxidation, and platelet aggregation by AGE, inhibits arterial plaque formation; AGE decreases homocysteine, lowers blood pressure, and increases microcirculation, which is important in diabetes, where microvascular changes increase heart disease and dementia risks. AGE also may help prevent cognitive decline by protecting neurons from Abeta neurotoxicity and apoptosis, thereby preventing ischemia- or reperfusion-related neuronal death and improving learning and memory retention. Although additional observations are warranted in humans, compelling evidence supports the beneficial health effects attributed to AGE in helping prevent cardiovascular and cerebrovascular diseases and lowering the risk of dementia and AD.

Transformation of mammalian cells in vitro by low doses of x-rays

X-irradiation of hamster embryo cells in culture, followed by cloning of the cells, was used to obtain a dose–response curve in terms of cell transformation. Transformations were observed for doses as low as 1 rad.

Transfection of rat embryo cells with mutant p53 increases the intrinsic radiation resistance

Dominant oncogenic sequences have been shown to modulate the intrinsic radiation sensitivity of cells of both human and murine tumor cell lines. Whether transfection with candidate tumor-suppressor genes can modulate intrinsic radiation sensitivity is unknown. The data presented here demonstrate that transfection of rat embryo cells with a mutant p53 allele can increase the intrinsic radiation resistance of cells in vitro. First, transfection with mutant p53 resulted in transformed cellular morphology. Second, the transfected clone and the corresponding pooled population of transfected clones were more resistant to ionizing radiation in vitro. Last, analyses of the parameters of cell kinetics suggested that the radiobiological effects were unlikely to be due to altered parameters of cell kinetics at the time of irradiation, suggesting that mutant p53 altered the intrinsic radiation resistance of transfected cells by a more direct mechanism. Further experimentation will be necessary to develop a mechanistic approach for the study of these alterations.

Free-Radical Processes in Multistage Carcinogenesis

Rodent and human cells in culture, transformed in vitro by radiation or chemicals into malignant cells, afford us the opportunity to probe into early and late events in the neoplastic process at a cellular and molecular level. Transformation can be regarded as an abnormal expression of cellular genes. The initiating agents disrupt the integrity of the genetic apparatus altering DNA in ways that result in the activation of cellular transforming genes (oncogenes) during some stage of the neoplastic process. Events associated with initiation and promotion may overlap to some degree, but in order for them to occur, cellular permissive conditions prevail. Permissive and potentiating factors include free radicals, and thyroid hormone, and inadequate antioxidants. Protective factors which suppress the carcinogenic process include enzymatic and dietary antioxidants. These are constitutive under normal circumstances and can be induced under conditions of oxidative stress produced by a wide range of carcinogens.

Regulation of retinol-binding protein metabolism in cultured rat liver cell lines

Abstract Retinol-binding protein (RBP), the plasma transport protein for vitamin A, is synthesized and secreted by the liver. In vitamin A deficiency, RBP secretion is blocked, leading to low serum and high liver levels of RBP. Administration of retinol to the intact rat stimulates a rapid secretion of RBP from liver into serum. We explored the use of a liver cell culture system to study the regulation of the synthesis and secretion of RBP. We found two lines of differentiated rat hepatoma cells, MH 1 C 1 and H 4 II EC 3 (H 4 ), that synthesized RBP during culture in vitro. The net synthesis of RBP was a function of the number of cells per dish and the duration of incubation. Both cell lines synthesized RBP when incubated in Neuman and Tytells Serumless Medium (NTS medium), while the MH 1 C 1 cells also synthesized RBP in Hams F-12 medium with added serum. A relatively large proportion (14–56%) of the RBP was retained within the cells when they were incubated in the vitamin A-free NTS medium alone. Addition of serum to NTS medium stimulated the release of RBP from the cells into the medium and also increased the net synthesis of RBP. These effects were not due to the increased adhesion of the cells to the petri dish. Addition of retinol (at levels of 0.35 or 3.5 nmole/ml) to the NTS medium resulted in the stimulation of RBP secretion from the cells into the medium and an increase in the net synthesis of RBP. By contrast, retinol had no effect on either the net synthesis or the cell-to-medium distribution of rat serum albumin. The data from these cell lines in culture suggest that retinol has a specific regulatory effect on RBP metabolism. These cells thus resemble the normal rat liver cell in vivo in regard to the known regulation of RBP metabolism.

Radiation oncogenesis in cell culture

Publisher Summary This chapter highlights the oncogenic effects of radiation with emphasis on ionizing radiation. In most cases, ionization occurs through electrically charged particles—which may be high-speed electrons or nuclear components such as protons or α- particles. These are directly ionizing radiations. They may originate from external or internal sources. They can also be generated inside the irradiated matter by indirectly ionizing radiations. Different types of ionizing radiation causes diverse biological effects. Comparison of various radiations in producing a particular effect is defined as the “relative biological effectiveness” (RBE) and is expressed as the ratio of the absorbed doses required to produce the same biological effect. Furthermore, the development of cell culture systems has made it possible to study the effects of radiation under defined conditions where complex homeostatic mechanisms do not prevail. Using in vitro systems free of host-mediated influences affords the opportunity to assess qualitatively and quantitatively dose-related and time-dependent interactions of radiation with single cells.

Cyclin D1 induced apoptosis maintains the integrity of the G1/S checkpoint following ionizing radiation irradiation

Cell cycle “checkpoints” help to ensure the integrity of normal cellular functions prior to replicative DNA synthesis and/or cell division. Cell kinetic abnormalities, particularly arrests at the G1/S and G2/M cell cycle checkpoints, are induced following exposure to ionizing radiationin vitro. Following irradiation, cellular signaling pathways may lead to G1 arrest and/or apoptosis at the G1/S cell cycle transition point. Transfection of cyclin D1, a G1/S cyclin, into a rat embryo cells (REC) results in cellular populations that overexpress cyclin D1, are transformed morphologically, demonstrate an increased incidence of apoptosis, and are tumorigenic in immune-deficient mice. Despite such phenotypic changes, transfected cell populations maintain the itegrity of the G1 checkpoint following ionizing radiation. The transfected cells overexpressing Cyclin D1 have a statistically significant increase in the incidence of apoptosis as compared to parental REC strains or mock-transfected REC. The work provides further evidence of Cyclin D1 playing a critical role in maintaining the integrity of the G1/S checkpoint, via the activation of apoptotic pathways following exposure to ionizing radiationin vitro.