Modifying role of Phyllanthus emblica and ascorbic acid against nickel clastogenicity in mice.
TL;DR: Aqueous extract of edible dried fruits of Phyllanthus emblica was fed to Mus musculus for seven consecutive days prior to treatment with different doses of nickel chloride, finding the greater efficacy of the fruit extract could be due to the interaction of its various natural components rather than to any single constituent.
About: This article is published in Cancer Letters.The article was published on 1991-07-26. It has received 59 citations till now. The article focuses on the topics: Dried fruit & Ascorbic acid.
Citations
More filters
TL;DR: This work challenges the common premise that direct genotoxic effects are central to nickel carcinogenesis and probably to that of other metals and proposes that it is formation of metal complexes with proteins and other molecules that changes cellular homeostasis and provides conditions for selection of cells with transformed phenotype.
Abstract: Nickel compounds are known to cause respiratory cancer in humans and induce tumors in experimental animals. The underlying molecular mechanisms may involve genotoxic effects; however, the data from different research groups are not easy to reconcile. Here, we challenge the common premise that direct genotoxic effects are central to nickel carcinogenesis and probably to that of other metals. Instead, we propose that it is formation of metal complexes with proteins and other molecules that changes cellular homeostasis and provides conditions for selection of cells with transformed phenotype. This is concordant with the major requirement for nickel carcinogenicity, which is prolonged action on the target tissue. If DNA is not the main nickel target, is there another unique molecule that can be attacked with carcinogenic consequences? Our recent observations indicate that ascorbate may be such a molecule. Nickel depletes intracellular ascorbate, which leads to the inhibition of cellular hydroxylases, manifested by the loss of hypoxia-inducible factor (HIF)-1α and - 2α hydroxylation and hypoxia-like stress. Proline hydroxylation is crucial for collagen and extracellular matrix assembly as well as for assembly of other protein molecules that have collagen-like domains, including surfactants and complement. Thus, the depletion of ascorbate by chronic exposure to nickel could be deleterious for lung cells and may lead to lung cancer.
74 citations
Cites background from "Modifying role of Phyllanthus embli..."
...2001); alleviation of clastogenic effects of Ni(II) in murine bone marrow (Dhir et al. 1991); and prevention of DNA damage and increase of viability of human lymphocytes cultured with Ni(II) (Osipova et al....
[...]
...…dismutase, catalase, and glutathione peroxidase activities in rats (Das et al. 2001); alleviation of clastogenic effects of Ni(II) in murine bone marrow (Dhir et al. 1991); and prevention of DNA damage and increase of viability of human lymphocytes cultured with Ni(II) (Osipova et al. 1998)....
[...]
TL;DR: The data indicate that the possible mechanism of inhibition by plant extract is mediated by its modulatory effect on hepatic activation and disposition processes.
Abstract: Benzo [α] pyrene (B[α]P) and cyclophosphamide (CP) are potent carcinogens/mutagens. Effect of Emblica officinalis extract administration on the in vivo genotoxi-city of B[α]P and CP was studied using bone marrow chromosomal aberration and micronucleus induction tests in mice.Three doses (50,250 and 500mg/kgbodyweight) oftheplant extractwere administered orallyfor 7 consecutive days prior to the administration of single dose of mutagens (B[α]P 125 mg/kg oral; CP 40 mg/kg i.p.).It was found that administration of 250 and 500 mg/kg of E. officinalis extract significantly inhibited the genotoxi-city of B [α] P as well as CP in both the assay systems. Administration of 50 mg/kg of the plant extract had no inhibitory effect.Vitamin C, a major constituent of E. officinalis when administered at dose level of 9 mg/kg b.w. (the approx-imate estimated amount present in the highest dose of plant extract, i.e. 500 mg) for 7 days did inhibit chromosomal aberrations and micronuclei induction, but not in a significant ma...
72 citations
TL;DR: A weight-of-evidence analysis of the relevant epidemiological, toxicological, and carcinogenic mode- of-action data for nickel compounds found the epidemiological evidence to be limited, in that some data suggest that exposure to soluble nickel compounds leads to increased cancer risk in the presence of certain forms of insoluble nickel.
Abstract: IARC is reassessing the human carcinogenicity of nickel compounds in 2009. To address the inconsistencies among results from studies of water-soluble nickel compounds, we conducted a weight-of-evidence analysis of the relevant epidemiological, toxicological, and carcinogenic mode-of-action data. We found the epidemiological evidence to be limited, in that some, but not all, data suggest that exposure to soluble nickel compounds leads to increased cancer risk in the presence of certain forms of insoluble nickel. Although there is no evidence that soluble nickel acts as a complete carcinogen in animals, there is limited evidence that suggests it may act as a tumor promoter. The mode-of-action data suggest that soluble nickel compounds will not be able to cause genotoxic effects in vivo because they cannot deliver sufficient nickel ions to nuclear sites of target cells. Although the mode-of-action data suggest several possible non-genotoxic effects of the nickel ion, it is unclear whether soluble nickel compounds can elicit these effects in vivo or whether these effects, if elicited, would result in tumor promotion. The mode-of-action data equally support soluble nickel as a promoter or as not being a causal factor in carcinogenesis at all. The weight of evidence does not indicate that soluble nickel compounds are complete carcinogens, and there is only limited evidence that they could act as tumor promoters.
69 citations
Cites background from "Modifying role of Phyllanthus embli..."
...…chromosomal aberrations or micronuclei was observed in mouse and hamster bone marrow cells by i.p.-injected nickel chloride (Chorvatovicova, 1983; Dhir et al., 1991; Mohanty, 1987), these effects were not observed in rat or mouse bone marrow cells by i.p.-injected nickel sulfate, nickel…...
[...]
...-injected nickel chloride (Chorvatovicova, 1983; Dhir et al., 1991; Mohanty, 1987), these effects were not observed in rat or mouse bone marrow cells by i....
[...]
TL;DR: The results showed that the cough suppressive activity of E. officinalis is dose-dependent, and a higher dose of this substance perorally was more effective, especially in decreasing the number of cough efforts, frequency of cough, and the intensity of cough attacks in inspirium and expirium was more pronounced.
63 citations
TL;DR: Emblica extract may be useful in reducing the side effects produced during therapeutic radiation, and the data clearly indicated that the extract significantly reduced the bioeffects of radiation.
Abstract: The radio protective effect of the fruit pulp of Emblica officinalis Gaertn (Emblica) was studied in adult Swiss albino mice. Mice were treated with 2.5 g/kg b.wt of Emblica for 10 consecutive days before irradiation and exposed to a single dose of 700 rads (7Gy) of radiation after the last dose. One group was given Emblica continuously for another 15 days after irradiation. Changes in the total leukocyte count, bone marrow viability and hemoglobin were studied after whole body irradiation. Administration of Emblica significantly increased these levels, which were lowered by irradiation. Animals were sacrificed at various time points after irradiation and the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPX), and glutathione-S-transferase (GST), and levels of glutathione were assayed in the blood. The damage to the cell membrane after whole body irradiation was studied by measuring the tissue lipid peroxides levels. Administration of Emblica significantly enhanced the activity of the various antioxidant enzymes and GST as well as glutathione system in the blood. Treatment with Emblica also lowered the elevated levels of lipid peroxides in the serum. The data clearly indicated that the extract significantly reduced the bioeffects of radiation. Emblica extract may be useful in reducing the side effects produced during therapeutic radiation.
62 citations
References
More filters
TL;DR: Dietary intake of natural antioxidants could be an important aspect of the body's defense mechanism against these agents of cancer and other age-related diseases.
Abstract: The human diet contains a great variety of natural mutagens and carcinogens, as well as many natural antimutagens and anticarcinogens. Many of these mutagens and carcinogens may act through the generation of oxygen radicals. Oxygen radicals may also play a major role as endogenous initiators of degenerative processes, such as DNA damage and mutation (and promotion), that may be related to cancer, heart disease, and aging. Dietary intake of natural antioxidants could be an important aspect of the body’s defense mechanism against these agents. Many antioxidants are being identified as anticarcinogens. Characterizing and optimizing such defense systems may be an important part of a strategy of minimizing cancer and other age-related diseases.
2,924 citations
01 Jan 1976
TL;DR: Micronuclei originate from chromatin which for different reasons has been lagging in anaphase, and in the course of telophase this material is included into one or the other daughter cell where it either can fuse with the main nucleus or form one or several secondary nuclei.
Abstract: Micronuclei originate from chromatin which for different reasons has been lagging in anaphase (Fig. la-d). In the course of telophase this material is included into one or the other daughter cell where it either can fuse with the main nucleus or form one or several secondary nuclei. These are, as a rule, considerably smaller than the principal nucleus and are therefore called micronuclei. Lagging has two main causes: chromosome breakage and malfunction of the spindle apparatus. In the first case the lagging elements are acentric chromosome fragments and di- or multicentrics connected by bridges, and in the second case they consist of entire chromosomes.
629 citations
479 citations
352 citations
TL;DR: In this chapter, inhibitors of mutagenesis and carcinogenesis that can arise as components of diet have been reviewed and most of the inhibitors have been demonstrated to be effective against a specific class of mutagens or carcinogens.
Abstract: Dietary inhibitors of mutagenesis and carcinogenesis are of particular interest because they may be useful for human cancer prevention. Several mutagenesis inhibitors have been demonstrated to be carcinogenesis inhibitors also, e.g., ellagic acid, palmitoleic acid, and N-acetylcysteine. This means that the search for mutagenesis inhibitors may be useful for discovering anticarcinogenic agents. Many mutagenesis inhibitors have been discovered by the use of short-term assays, particularly the Ames Salmonella test. This simple in vitro system has provided opportunities to elucidate the mechanisms of inhibition. The elucidation of the mechanism may allow us to infer the possible anticarcinogenic activity of the reagent. In this chapter, inhibitors of mutagenesis and carcinogenesis that can arise as components of diet have been reviewed. Most of the inhibitors have been demonstrated to be effective against a specific class of mutagens or carcinogens. Therefore, it may be argued that these inhibitors are antagonistic only to those particular agents. Here again, understanding of the mechanisms of these inhibitions is necessary for the assessment. Dietary inhibitors reviewed in this article include: (1) as inhibitors of mutagenesis: porphyllins, fatty acids, vitamins, polyphenols, and sulfhydryl compounds, (2) as inhibitors of carcinogenesis: vitamins A, E and C, ellagic acid, sulfhydryl compounds, fats, selenium, calcium, and fiber. Further studies in this area of science appear to help establish the recipe of a healthy diet.
310 citations