Copper toxicity, oxidative stress, and antioxidant nutrients.

Turmeric, derived from the plant Curcuma longa, is a gold-colored spice commonly used in the Indian subcontinent, not only for health care but also for the preservation of food and as a yellow dye for textiles. Curcumin, which gives the yellow color to turmeric, was first isolated almost two centuries ago, and its structure as diferuloylmethane was determined in 1910. Since the time of Ayurveda (1900 Bc) numerous therapeutic activities have been assigned to turmeric for a wide variety of diseases and conditions, including those of the skin, pulmonary, and gastrointestinal systems, aches, pains, wounds, sprains, and liver disorders. Extensive research within the last half century has proven that most of these activities, once associated with turmeric, are due to curcumin. Curcumin has been shown to exhibit antioxidant, anti-inflammatory, antiviral, antibacterial, antifungal, and anticancer activities and thus has a potential against various malignant diseases, diabetes, allergies, arthritis, Alzheimer's disease, and other chronic illnesses. These effects are mediated through the regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases, and other enzymes. Curcumin exhibits activities similar to recently discovered tumor necrosis factor blockers (e.g., HUMIRA, REMICADE, and ENBREL), a vascular endothelial cell growth factor blocker (e.g., AVASTIN), human epidermal growth factor receptor blockers (e.g., ERBITUX, ERLOTINIB, and GEFTINIB), and a HER2 blocker (e.g., HERCEPTIN). Considering the recent scientific bandwagon that multitargeted therapy is better than monotargeted therapy for most diseases, curcumin can be considered an ideal "Spice for Life".

Curcumin: The Indian solid gold

Arsenic toxicity and potential mechanisms of action

The Analysis of Variance.

The effect of elevated temperature on mortality is a public health threat of considerable magnitude. Every year, a large number of hospitalizations and deaths occur in association with exposure to elevated ambient temperatures (1, 2). An average of 400 deaths annually are counted as directly related to heat in the United States, with the highest death rates occurring in persons aged 65 years or more (3). The actual magnitude of heat-related mortality may be notably greater than what has been reported, since we do not have widely accepted criteria for determining heat-related death (4, 5–7), and heat may not be listed on the death certificate as causing or contributing to death. Persons living in urban environments may be at particularly increased risk for mortality from ambient heat exposure, since urban areas typically have higher heat indexes (combinations of temperature and humidity (8)) than surrounding suburban or rural areas, a phenomenon known as the “urban heat island effect” (9). Moreover, urban areas retain heat during the night more efficiently (10). Thus, as the US population becomes more urbanized and the number of elderly people continues to increase (11), the threat of heat-related mortality will probably become more severe. Many of these deaths may be preventable with adequate warning and an appropriate response to heat emergencies, but preventive efforts are complicated by the short time interval that may elapse between high temperature exposure and death. Thus, prevention programs must be based around prospective and rapid identification of high-risk conditions and persons. We carried out this review to assess the current epidemiologic evidence available for this purpose.

Relation between Elevated Ambient Temperature and Mortality: A Review of the Epidemiologic Evidence

Cobalt, a transition element, is an essential component of several enzymes and co-enzymes. It has been shown to affect growth and metabolism of plants, in different degrees, depending on the concentration and status of cobalt in rhizosphere and soil. Cobalt interacts with other elements to form complexes. The cytotoxic and phytotoxic activities of cobalt and its compounds depend on the physico-chemical properties of these complexes, including their electronic structure, ion parameters (charge-size relations) and coordination. Thus, the competitive absorption and mutual activation of associated metals influence the action of cobalt on various phytochemical reactions. The distribution of cobalt in plants is entirely species-dependent. The uptake is controlled by different mechanisms in different species. Biosorption involves ion-exchange mechanism in algae, but in fungi both metabolism-independent and -dependent processes are operative. Physical conditions like salinity, temperature, pH of the medium, and presence of other metals influence the process of uptake and accumulation in algae, fungi, and mosses. Toxic concentrations inhibit active ion transport. In higher plants, absorption of Co2+ by roots involves active transport. Transport through the cortical cells is operated by both passive diffusion and active process. In the xylem, the metal is mainly transported by the transpirational flow. Distribution through the sieve tubes is acropetal by complexing with organic compounds. The lower mobility of Co2+ in plants restricts its transport to leaves from stems. Cobalt is not found at the active site of any respiratory chain enzymes. Two sites of action of Co2+ are found in mitochondrial respiration since it induces different responses toward different substrates like α-keto glutarate and succinate. In lower organisms, Co2+ inhibits tetraphyrrole biosynthesis, but in higher plants it probably participates in chlorophyll b formation. Exogenously added metal causes morphological damage in plastids and changes in the chlorophyll contents. It also inhibits starch grain differentiation and alters the structure and number of chloroplasts per unit area of leaf. The role of cobalt in photosynthesis is controversial. Its toxic effect takes place by inhibition of PS2 activity and hence Hill reaction. It inhibits either the reaction centre or component of PS2 acceptor by modifying secondary quinone electron acceptor Qb site. Co2+ reduces the export of photoassimilates and dark fixation of CO2. In C4 and CAM plants, it hinders fixation of CO2 by inhibiting the activity of enzymes involved. Cobalt acts as a preprophase poison and thus retards the process of karyokinesis and cytokinesis. The action of cobalt on plant cells is mainly turbagenic. Cobalt compounds act on the mitotic spindle, leading to the formation of chromatin bridges, fragmentation, and sticky bridges at anaphase and binucleate cells. High concentrations of cobalt hamper RNA synthesis, and decrease the amounts of the DNA and RNA probably by modifying the activity of a large number of endo- and exonucleases. The mutagenic action of cobalt salts results in mitochondrial respiratory deficiency in yeasts. In cytokinesis-deficient mutant of Chlamydomonas it increases the amount of sulfhydryl compounds. Cobalt has been shown to alter the sex of plants like Cannabis sativa, Lemna acquinoclatis, and melon cultivars. It decreases the photoreversible absorbance of phytochrome in pea epicotyl and interferes with heme biosynthesis in fungi. Low concentration of Co2+ in medium stimulates growth from simple algae to complex higher plants. Relatively higher concentrations are toxic. A similar relationship is seen with crop yield when the metal is used in the form of fertilizer, pre-seeding, and pre-sowing chemicals. Toxic effect of cobalt on morphology include leaf fall, inhibition of greening, discolored veins, premature leaf closure, and reduced shoot weight. Being a component of vitamin B12 and cobamide coenzyme, Co2+ helps in the fixation of molecular nitrogen in root nodules of leguminous plants. But in cyanobacteria, CoCl2 inhibits the formation of heterocyst, ammonia uptake, and nitrate reductase activity. The interaction of cobalt with other metals mainly depends on the concentration of the metals used. For example, high levels of Co2+ induce iron deficiency in plants and suppress uptake of Cd by roots. It also interacts synergistically with Zn, Cr, and Sn. Ni overcomes the inhibitory effect of cobalt on protonemal growth of moss, thus indicating an antagonistic relationship. The beneficial effects of cobalt include retardation of senescence of leaf, increase in drought resistance in seeds, regulation of alkaloid accumulation in medicinal plants, and inhibition of ethylene biosynthesis. In lower plants, cobalt tolerance involves a cotolerance mechanism. The mechanism of resistance to toxic concentration of cobalt may be due to intracellular detoxification rather than defective transport. In higher plants, only a few advanced copper-tolerant families showed cotolerance to Co2+. Tolerance toward Co2+ may sometimes determine the taxonomic shifting of several members of Nyssaceae. Due to the high cobalt content in serpentine soil, essential element uptake by plants is reduced, a phenomenon known as “serpentine problem,” for New Caledonian families like Flacourtiaceae. Large amounts of calcium in soil may compensate for the toxic effects of heavy metals in adaptable genera grown in this type of soil. The biomagnification of potentially toxic elements, such as cobalt from coal ash or water into food webs, needs additional study for effective biological filtering.

Effects of cobalt on plants

Aluminum toxicity is a major factor in limiting growth in plants in most strongly acid soils. Toxic effects on plant growth have been attributed to several physiological and biochemical pathways, although the precise mechanism is still not fully understood. In general, root elongation is hampered through reduced mitotic activity induced by Al, with subsequent increase in susceptibility to drought. The initial site of uptake is usually the root cap and the mucilaginous secretion covering the epidermal cells. Al ions bind very specifically to the mucilage by exchange adsorption on the polyuronic acid, complexing with the pectic substances and by the formation of polyhydroxy forms, increasing the number of Al atoms per positive charge. Toxicity has been suggested to be initiated at the sites of mucopolysaccharide synthesis. Al is absorbed on all Ca-binding sites on the cell surface. In the intact tissues, most of the Al is bound to the pectic substances of the cell wall and a part to the nucleic acids and cell membrane. Al is also reported to enter the plant by moving into meristematic cells via the cortex, bypassing the endodermal barrier. Being a polyvalent cation, it follows principally the apoplasmic pathway of transport through cortical cells, but may also enter the stele through the plasmalemma. Ultrastructural studies have shown the maximum accumulation to be in the epidermal and cortical cells. The interaction of Al with different systems follows different pathways. The plasma membrane at the outer boundary of the root cell is a potential target and its physical properties can be altered by Al through interaction with membrane-bound ATPase, lipids, carbohydrates and proteins. The Golgi apparatus has been suggested as the primary site of action, followed by damage to the plasmalemma. Aluminum interferes with the uptake, transport and use of several essential elements, including Cu, Zn, Ca, Mg, Mn, K, P and Fe. Excess of Al reduces the uptake of certain elements and increases that of others, the patterns being dependent on the element, the plant part and species involved. A major factor is the pH concentration. At an acid pH, below 5.5, the antagonism between Ca and Al is probably the most important factor affecting Ca uptake by plants. The molecular mechanism of tolerance of Al is as yet not clear. Tolerant plants reduce the absorption by the root or detoxify Al after absorption. Al tolerant plants may be grouped into those with higher Al concentrations in tops and those with less. In the latter, more Al is entrapped in roots. Uptake of Al may be reduced by binding to cell wall or to membrane lipid. Tolerance may be different in different species and seems to be controlled by one or more genes. Absorption of Al in non-metabolic conditions is affected only slightly by temperature. Anaerobic conditions, like the presence of nitrogen and metabolic inhibitors, damage the endodermal membrane barrier, increasing the uptake and enhancing injurious effects. Aluminum also causes morphological damage to plant parts. It affects photosynthesis by lowering chlorophyll content and reducing electron flow. Reduced respiratory activity might be due to reduced metabolic energy requirement. Protein synthesis is decreased probably due to effect on ribosome distribution at endoplasmic reticulum. Aluminum is known to bind to DNA and nuclei. However, its penetrance to DNA of mitotically active centers is slow. On accumulating in roots, it initially inhibits mitotic activity, possibly through affecting the integrated control function of the root meristem. Aluminum toxicity in acid soil is of special importance due to the destruction of components of forest ecosystems under specific conditions. It reduces biomass yield and tree growth and represses litter-degrading microflora. Further information is required on the factors affecting membrane permeability, distribution and accumulation of Al in different plant parts and different species. Al tolerance may be studied with relation to the presence of different ligands, nitrogen metabolism (nitrate reductase and protein accumulation), nitrogen tolerance in relation to pH change and metal ion activities, the role of Ca and P and interference with water relations and litter degradation.

Some aspects of aluminum toxicity in plants

Lanthanum belongs to the group of elements known as "lanthanons," which also includes cerium, europium, promethium, and thulium. It is the most electropositive element of the rare earth group, is uniformly trivalent, and is similar in its chemical properties to the alkaline earth elements. The effects of this element and its compounds on cellular systems are of considerable interest because of their increasing use in industry and as a substitute or antagonist for calcium in a variety of cellular reactions. Lanthanum is also being employed extensively in studying anatomical barriers, membrane structure, and subcellular transport systems, particularly the calcium pathway.

Effects of lanthanum in cellular systems - A review

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.

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

An analysis of the available data on the clastogenic effects of metals and their compounds on higher organisms indicates some general trends. Following chronic exposure to subtoxic doses, a decrease in mitotic frequency and an increase in the number of chromosomal abnormalities are observed. These effects are usually directly proportional to the dose applied and the duration of treatment within the threshold limits. Recovery after acute treatment is inversely related to the dosage. The ultimate expression of the effects depends on certain factors, including the mode and vehicle of administration; the form administered; the test system used; the rate of detoxification, distribution, and retention in the different tissues; and interaction with foreign and endogenous substances as well as the mode of action with the biological macromolecules. In mammals, the clastogenic activity of the metals within each vertical group of the periodic table is directly proportional to the increase in atomic weight, electropositivity, and solubility of the metallic cations in water and lipids, except for Li and Ba. This pattern of inherent cytotoxicity increases with successive periods in the horizontal level. It is enhanced by the formation of covalent and coordinate covalent complexes by heavy metals with the biological macromolecules. In plants, the solubility of the metals in water is of much greater importance. The degree of dissociation of metallic salts and the rate of absorption affect significantly the frequency of chromosomal aberrations. In assessing the effects of environmental metal pollution, the presence of other metals and toxic chemicals and the level of nutrition should be taken into account, since in nature, metals occur in combination and these factors modify the cytotoxic effects to a significant extent.

Geeta Talukder

Papers

Effects of cobalt on plants

Some aspects of aluminum toxicity in plants

Effects of lanthanum in cellular systems - A review

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

Effects of metals on chromosomes of higher organisms.