Protection against cytotoxic effects of arsenic by dietary supplementation with crude extract of Emblica officinalis fruit.

Dietary administration of a crude aqueous extract of Emblica officinalis Gaertn. fruit reduced significantly the cytotoxic effects of sodium arsenite administered orally. The crude extract (685 mg/kg bw) was given daily by gavaging to age and sex matched laboratory bread Swiss albino mice for 7 and 14 days, followed by a single dose of sodium arsenite (2.5 mg/kg bw = 1/10 of LD(50)). The animals were killed after 24 h and chromosome preparations made following a schedule of colchicine-fixative-air drying-Giemsa. The endpoints screened were chromosomal aberrations and damaged cells. The crude extract reduced arsenic damage bringing the cells almost to the normal level.

Prevention of cytotoxic effects of arsenic by short-term dietary supplementation with selenium in mice in vivo.

Interaction between selenium and arsenic has been used to protect against the genotoxic effects of sodium arsenite through dietary intervention by an equivalent amount (1/10 LD50) of sodium selenite. The two salts were administered by gavaging to laboratory bred Swiss albino mice sequentially and in combination. Cytogenetic endpoints, including chromosomal aberrations (CA) and damaged cells (DC) were recorded 24 h after exposure from chromosome spreads in bone marrow cells. Administration of sodium selenite 1 h before sodium arsenite reduced the clastogenic effects of the latter significantly. The protection was less when the salts were given together and negative when arsenite was given before selenite. Histological changes were recorded. Such reduction of arsenic toxicity through dietary intervention by selenium is of significance in protecting against the widespread toxicity observed in human populations exposed to arsenic through drinking water from contaminated deep tubewells in West Bengal and Bangladesh.

Inhibition of clastogenic effects of arsenic through continued oral administration of garlic extract in mice in vivo.

Crude aqueous extract of garlic bulbs (Allium sativum L. single clove variety) was administered by gavage to mice of both sexes daily for up to 30 and 60 days, in doses corresponding to 6 g for a 60 kg human body. Sodium arsenite (at 1/50 of LD50 dose) was injected subcutaneously to mice on every 7th day of the experiment. Chromosome preparations made from bone marrow following flame drying Giemsa schedule were screened for chromosomal aberrations. The clastogenic affects of prolonged exposure to sodium arsenite --a strong clastogen-- was reduced by a highly significant amount when crude garlic extract, in the dose used, was given daily to the mice by intubation for the same period.

Dietary chemoprevention of clastogenic effects of 3,4-benzo(a)pyrene by Emblica officinalis Gaertn. fruit extract.

Dietary supplementation with extract of fruit of Emblica officinalis Gaertn. (a rich source of vitamin C) to mice in vivo significantly reduced the cytotoxic effects of a known carcinogen, 3,4-benzo(a)pyrene. Age-matched Swiss albino mice were fed by gavaging the fruit extract daily for 28 days. From day 9, one dose of the carcinogen was given on alternate days up to a total of eight doses. On day 29, all mice were transferred to normal diet. Control sets received the extract alone, the carcinogen alone and olive oil alone. All mice were sacrificed at 12 weeks and 14 weeks after the end of the experiment. Chromosome preparations were made from bone marrow after the usual colchicine-hypotonic-fixative-air drying-Giemsa staining schedule. Cytogenetic end points screened were the frequencies of chromosomal aberrations and of damaged cells induced. The cytotoxic effects were significantly lower in the mice given the fruit extract with the carcinogen than in those given the carcinogen alone.

Chlorophyll and chromosome breakage.

Increased consumption of green vegetables in the diet has been associated with protection against carcinogenic effects and related mutagenic and clastogenic (chromosome breaking) activity of genotoxic agents. Chlorophyll, present in all green plant parts, has been suggested to be a major protective factor in the process. We have, however, observed that while a crude aqueous extract of Indian spinach leaf significantly reduced genotoxic effects, chlorophyll alone was ineffective. On the other hand, chlorophyll, both as an aqueous extract from the leaf and in a purified commercial form, induced a significantly high frequency of chromosome breaks in bone marrow cells of mice on oral administration. The crude aqueous extract of the leaf was non-toxic. The protective activity of the crude leaf extract may be attributed to the total effect of the interaction between different components, in which the clastogenicity of chlorophyll has been neutralized.

Dietary garlic extract in modifying clastogenic effects of inorganic arsenic in mice: two-generation studies.

Mice are fed by gavage crude garlic extract (100 mg/kg b.wt.) for 30 consecutive days. One set was administered sodium arsenite (0.1 mg/kg b.wt.) simultaneously. Another set was treated with sodium arsenite only. Mice given distilled water were kept as negative control. Exposed mice from each set were sacrificed and bone marrow preparations examined for chromosomal aberrations and damaged cells. Sodium arsenite is a strong clastogen and the effects were reduced to a significant level by prolonged administration of garlic extract. For F1 studies, exposed male mice were mated with exposed female mice, and the progeny examined. In the progeny, clastogenic effects of sodium arsenite persisted in a lower degree, indicating that the metal is able to cross the transplacental barrier. There was no statistically significant difference between the effect in progeny of parents only given sodium arsenite when given simultaneously for prolonged periods in the parents; however, the effect is meagre in the next generation.

Clastogenic activity of pure chlorophyll and anticlastogenic effects of equivalent amounts of crude extract of Indian spinach leaf and chlorophyllin following dietary supplementation to mice.

Dietary consumption of green vegetables has been associated with protection against mutagenic and clastogenic activity of genotoxicants. Chlorophyll, being present in all green plants, had earlier been suggested to be the principal factor involved. Mice were administered (i) crude aqueous extract of leaf of Indian spinach, Beta vulgaris L. var.benghalensis Hort., and equivalent amounts of (ii) chlorophyll extracted from the leaf; (iii) purified chlorophyll, (iv) chlorophyllin, a sodium-copper derivative of chlorophyll; daily for 7 days. On day 7, one set of mice from each treatment was administered potassium dichromate-a known metallic clastogen. The mice were sacrificed after 24 hours. Chromosome preparations were made from bone marrow following the usual colchicine-air dry-Giemsa schedule. The cytogenetic endpoints scored were chromosomal aberrations and damaged cells. Crude leaf extract and chlorophyllin were nonclastogenic and reduced the clastogenic effects of potassium dichromate to the control distilled water level. Chlorophyll alone, whether extracted from the leaf or obtained in commercially purified form, was clastogenic and could reduce the effects of the chromium salt only to its own level. The protective action of the crude leaf extract may be attributed to the total effect of the interaction between the different components within the leaf extract, in which the clastogenicity of chlorophyll had been neutralized.

Effects of crude garlic extract on mouse chromosomes in vivo.

Three concentrations (25, 50 and 100 mg/kg body weight) of fresh garlic (Allium sativum L.) were administered daily by gavage to Swiss albino mice for different durations up to 60 days. These concentrations had been observed to protect significantly against effects of known clastogens. The endpoints scored were frequencies of chromosomal aberrations and damaged cells induced in bone marrow preparations. These parameters were found to be directly dose dependent and after an initial enhancement at 7 days, were reduced following prolonged exposure for 30 and 60 days to the low level observed at 24 hr. Therefore, administration of a low concentration of garlic extract daily is suggested for at least 30 days to obtain the maximum benefit of the extract in protecting against the clastogenic effects of known genotoxicants.

Chlorophyll and chlorophyllin as modifiers of genotoxic effects.

Reports on an inverse relationship between the consumption of fresh vegetables and human gastrointestinal cancer have been followed by screening for the protective activity of a large number of plant extracts, including leafy vegetables. Chlorophyll is ubiquitous in all green plant parts. Chlorophyllins are derivatives of chlorophyll in which the central magnesium atom is replaced by other metals, such as cobalt, copper or iron. An attempt has been made in this article to review the relative efficacy of chlorophyll and chlorophyllin in modifying the genotoxic effects of various known toxicants.

Modification of clastogenicity of three known clastogens by garlic extract in mice in vivo.

The anticlastogenic activity of crude extract of garlic (Allium sativum L.) was studied in bone marrow cells of mice. Male laboratory-bred Swiss albino mice were given one of three concentrations of the freshly prepared extract (100 mg, 50 mg, and 25 mg/kg body weight) as a dietary supplement by gavage for 6 consecutive days. On the seventh day the mice were administered a single acute dose of two known clastogens, mitomycin C(1.5 mg/kg) and cyclophosphamide (25 mg/kg) or sodium arsenite (2.5 mg/kg), simultaneously with garlic extract. After 24 hr, chromosome preparations were made from the bone marrow cells. The endpoint studied were chromosomal aberrations and damaged cells. Garlic extract alone induced a low level of chromosomal damage. The clastogenicity of all three mutagens were reduced significantly in the animals which had been given garlic extract as dietary supplement. The extent of reduction was different for the three clastogens and may be attributed to the interaction with the different components of the extract.

Relative protection given by extract of Phyllanthus emblica fruit and an equivalent amount of vitamin C against a known clastogen--caesium chloride.

Aqueous extracts of Phyllanthus emblica L. fruit and an equivalent amount of vitamin C were administered orally by gavage to laboratory-bred Swiss albino mice for 7 days in order to evaluate the protection afforded by the two extracts against clastogenic effects of different doses of caesium chloride (CsCl) on bone marrow cells of Mus musculus in vivo. Both pretreatments significantly reduced the frequency of chromosome aberrations induced by CsCl given at three different doses, indicating that vitamin C, an essential component of P. emblica extract, was the effective agent in protecting against the clastogenicity of the metal salt.

Modifying role of Phyllanthus emblica and ascorbic acid against nickel clastogenicity in mice.

Nickel, a major environmental pollutant is known for its clastogenic and carcinogenic potential. Dietary inhibitors of mutagenesis and carcinogenesis are of particular importance since they may have a role in cancer prevention. In the present investigation, aqueous extract of edible dried fruits of Phyllanthus emblica, a well known medicinal plant, was fed to Mus musculus for seven consecutive days prior to treatment with different doses of nickel chloride (10, 20 and 40 mg/kg body wt.); the fruit extract significantly reduced the frequency of CA/cell, the percentage of aberrant cells and the frequency of micronuclei induced by all doses of nickel in the bone marrow cells of mice. Ascorbic acid, a major constituent of the fruit, fed for 7 consecutive days in equivalent concentration as that present in the fruit, however, could only alleviate the cytotoxic effects induced by low doses of nickel; at the higher doses it was ineffective. The greater efficacy of the fruit extract could be due to the interaction of its various natural components rather than to any single constituent. The study assumes importance in view of the widespread human exposure to nickel compounds.

Modification of clastogenicity of lead and aluminium in mouse bone marrow cells by dietary ingestion of Phyllanthus emblica fruit extract.

Extract of Phyllanthus emblica fruit and ascorbic acid were evaluated separately for protection against clastogenicity induced by lead (Pb) and aluminium (Al) salts on mouse bone marrow chromosomes. Oral administration of Phyllanthus fruit extract (PFE) for 7 days before exposure to both metals by intraperitoneal injection increased the frequency of cell division and reduced the frequency of chromosome breaks significantly. Comparable doses of synthetic ascorbic acid (AA) were less effective and could protect against the effects of Al and only a low dose of Pb (10 mg/kg body weight). AA administered before treatment in mice given higher doses of Pb (40 mg/kg body weight) enhanced the frequency of chromosome breaks, giving a synergistic effect. The higher protection afforded by PFE may be due to the combined action of all ingredients, rather than to AA alone.

Betel cytotoxicity.

An attempt to summarise the phytochemical composition of the betel quid, formation of N-nitrosation products during chewing, results of carcinogenicity and mutagenicity studies and the relationship between betel chewing and submucous fibrosis have been made from presently available literature. The present review provides a better understanding of the capacity of the quid ingredients in inducing preneoplastic changes for evaluation of the risk involved with its chewing.

Effect of selenium on cadmium-induced chromosomal aberrations in bone marrow cells of mice.

Selenium, which is regarded as nature's antidote to heavy metal toxicities, was administered to mice. Salt solutions of cadmium chloride and sodium selenite were gavaged singly and successively, with or without a time gap of 1 h. Degrees of protection offered by this element against cadmium-induced toxic effects with special reference to chromosomal aberrations were assessed.

Antagonistic and synergistic effects of lead and selenium in Rattus norvegicus.

Female rats were administered intraperitoneal injections of solutions of lead acetate and sodium selenite. The salt solutions were given singly to 'control' animals and successively to the 'treated' animals in both chronic and acute treatments but with or without a time gap of 1 h in the latter treatment. In the chronic treatments the dosage of lead acetate was kept constant and that of sodium selenite varied while in the acute treatments the ratio of the two salts was kept constant. Degrees of protection afforded by sodium selenite against chromosomal damage caused by lead acetate were assessed.

Effects of mercury-selenium antagonism on mammalian cell division.

Various combinations of HgCl2 and sodium selenite were administered orally to rats and mice in vivo for both chronic and acute treatment. The antagonistic interaction and the optimum combination at which the action of HgCl2 could be neutralised by Na2SeO3 was investigated. Of the concentrations employed in rats when Na2SeO3 was fed after 1 h treatment with HgCl2, the percentage of chromosomal abnormalities significantly decreased as compared to animals treated with HgCl2 alone. All other experiments with different combinations of HgCl2 and Na2SeO3 gave higher frequencies of chromosomal abnormalities as compared to Na2SeO3 alone. An acute dose of HgCl2 was lethal, but in combination with Na2SeO3 at 1 h intervals, the abnormalities decreased to 60%. The results with mice showed antagonism in mixtures at higher doses, which was not evident in lower doses.