The level of polyaromatic hydrocarbons in kajal and surma of major Indian brands.

Kajal and surma are eye cosmetics extensively used in Indian subcontinent. Kajal is prepared by burning of vegetable oil and butter oil while surma by grinding of the stones. High performance liquid chromatography and gas chromatography-mass spectrometry instruments were used for quantification and confirmation of 16 polyaromatic hydrocarbons (PAHs). Significant concentration of PAH was found in all the samples examined. The median concentration of PAH ranged from 0.14 (lowest, anthracene) to 31.18 microg g(-1) [dibenz(a,h)anthracene] in kajal sample and from not detectable concentration (naphthalene) to 197.47 microg g(-1) of benzo(a)pyrene in surma sample. Fifteen PAHs were detected in all the samples. Therefore the use of kajal and surma in eye should be strictly restricted.

Interaction of lead with some essential trace metals in the blood of anemic children from Lucknow, India.

BACKGROUND: The effects of lead on the hematological system results in the inhibition of heme synthesis and in anemia. Lead may affect the absorption and metabolism of essential trace metals also. There is little information especially from the northern region of India regarding the relationship between blood lead levels>or=10 microg/dl and anemia in children. We performed a cross-sectional study to evaluate the association of blood lead levels>or=10 microg/dl with anemia, and its effect on hematological system and some essential trace metals in children. METHODS: A total of 75 children aged 1-7 years, 50 anemic (Hb8 g%), drawn from Lucknow, India and nearby areas were recruited to determine blood levels of lead, iron, zinc, copper, and calcium along with hematological parameters [delta-aminolevulinic acid dehydratase (delta-ALAD) hemoglobin (Hb), hematocrit, and ascorbic acid]. RESULTS: Based on Centre for Disease Control and Prevention's intervention level of blood lead, children were categorized into those with blood lead<10 microg/dl (6.89+/-2.44) (n=19) (GI) and those with blood lead<10 microg/dl (21.86+/-7.58) (n=56) (GII). After adjustment for child's age, sex, and area of residence, children with blood lead levels>or=10 microg/dl were 2.87 (95% CI: 1.60-2.87) times as likely to have anemia as children with blood lead levels<10 microg/dl. The differences of the adjusted mean values of Hb, delta-ALAD, and hematocrit were significantly lower in children from the GII group when compared to children from the GI group (p<0.01, p<0.01, and p<0.05, respectively). Among essential trace metals, adjusted mean levels of blood iron, zinc, and calcium were significantly lower in GII as compared to GI (P<0.05 each). There were significant negative correlations of blood lead levels with delta-ALAD (r=-0.612, p<0.01), hematocrit (r=-0.427, p<0.05), iron (r=-0.552, p<0.05) zinc (r=-0.427, p<0.05), and calcium (r=-0.324, p<0.05). CONCLUSION: Results indicate that elevated blood lead levels (>or=10 microg/dl) in children were significantly associated with risk of anemia and that blood lead levels also influenced the status of essential trace metals. However, results of this study may be limited due to limited sample size but certainly form the basis of a larger sample size study, taking into account all the known potential confounders of anemia in children.

Distribution of chromium in poisoned rats.

The effect of dose and duration of treatment with chromium on its distribution in certain vital organs and the blood of rats has been investigated. The accumulation of metal was highest in liver and kidneys, followed by testes, brain and blood and was rather more dependent on the dose than on the duration of exposure. The sub-cellular distribution in liver revealed greater concentration of the metal in the nuclear fraction than in the mitochrondrial or the post mitochondrial fraction. The uptake of the metal by the mitochondrial fraction however, increased with the increase in the dose of chromium from 1 mg/kg to 2 or 3 mg/kg.

Time-dependent protective effect of selenium against cadmium-induced nephrotoxicity and hepatotoxicity.

The role of selenium in protection against nephrotoxicity and hepatotoxicity of cadmium in rats was investigated. The administration of Cd (3 mg/kg, s.c.) for 3 days enhanced the urinary excretion of lactic dehydrogenase (LDH), glutamic oxaloacetic transaminase (GOT) and total proteins, decreased the renal activity of GOT and alkaline phosphatase (ALP) and increased the renal level of Cd, Cu and Zn. Cadmium also increased the serum GOT and glutamic pyruvic transaminase (GPT), decreased the hepatic activity of GOT and GPT and increased the hepatic level of Cd and Zn. The concomitantly administered Se (2 mg/kg, i.p.) initially reduced most of these Cd-induced alterations. The results show protection by Se against nephrotoxicity and hepatotoxicity of Cd on the 4th day of the commencement of Cd administration, but the signs of Cd intoxication were observed on the 8th day.

Effect of zinc on cadmium, copper and zinc contents in cadmium exposed rats.

The effect of zinc (Zn) administration on the uptake and retention of cadmium (Cd), copper (Cu) and Zn in liver, kidneys and testes of cadmium exposed rats was investigated. Exposure to Cd caused a significant increase in the uptake of these metals in the 3 organs. The administration of Zn after the Cd exposure had little effect on the level of these metals.

Mobilization of cadmium by liposome-encapsulated meso-2,3-dimercaptosuccinic acid in pre-exposed mice.

meso-2,3-Dimercaptosuccinic acid (DMSA) treatment in free of liposome-encapsulated form was given to mice pre-exposed to cadmium as CdCl2 (2 intraperitoneal injections; 0.5 mg Cd/kg along with 5 microCi 109CdCl2 in 4 ml volume within 24 h). Both treatments removed cadmium from liver, spleen, testis and blood with liposomal DMSA exhibiting higher efficacy in mobilizing cadmium not only from whole organs but also from liver proteins. It also resulted in higher excretion of cadmium via urine as compared with free DMSA or saline treatment. Whereas this treatment eliminated significantly higher amounts of cadmium via the fecal route throughout the period examined, free DMSA responded only 48 h after treatment and was less effective. The results suggest mobilization of cadmium from intracellular sites of deposition. However, DMSA in the dose administered (24 mumol/kg i.v.) in either form was ineffective in decorporating cadmium from the kidney, the critical organ in cadmium intoxication.

Evaluation of LD50 of some polyaminocarboxylic acids used as chelating drugs in metal intoxication.

The LD50 of the following metal-binding chelating drugs, EDTA, diethylenetriaminepentaacetic acid (DTPA), hydroxyethylenediaminetriacetic acid (HEDTA), cyclohexanediaminotetraacetic acid (CDTA) and triethylenetetraminehexaacetic acid (TTHA) was evaluated in terms of mortality in rats after intraperitoneal administration and was found to be in the order: CDTA greater than EDTA greater than DTPA greater than TTHA greater than HEDTA. A possible correlation between the toxicity and molecular structure of the compounds is discussed.

Pattern of urinary 63Ni excretion in rats.

The elution profile of urine from rats given 63Ni i.p. using a Sephadex G-25 column was studied to investigate the chemical form and pattern of nickel (Ni) excretion. Ni was excreted probably as a mixture of complexes with chemical constituents of urine (molecular weight 200-250) within 24 h after 63Ni injection. 63Ni increased significantly the excretion of proteins, absorbing at 280 nm, which were not associated with Ni. The administration of N-acetyl-DL-penicillamine 24 h after 63Ni injection increased significantly the urinary excretion of the metal and restored proteinuria during the next 24 h. It could not be ascertained whether N-acetyl-DL-penicillamine enhanced urinary excretion of 63Ni by forming an excretable complex or by modifying the excretory pathway.

Protective role of trace metals in lead intoxication.

Protective effect of copper (Cu), zinc (Zn) or cobalt (Co) against lead (Pb) toxicity in rats was investigated. Trace metal administration together with Pb decreased the hepatic and renal uptake of lead and reduced the Pb-induced inhibition of blood delta-aminolevulinic acid dehydratase (delta-ALAD) activity. The hepatic uptake of Zn or Co was also increased in animals administered Pb and Zn or Pb and Co, respectively. However, no significant difference could be observed between the protective effects of three essential trace metals examined against lead toxicity.

Vitamin B complex in treatment of cadmium intoxication.

The effect of vitamin B-complex on cadmium nephrotoxicity and hepatotoxicity was investigated in rats. The administration of Cd (3 mg per kg, s.c., three days) increased the urinary excretions of lactic dehydrogenase (LDH), glutamic oxalacetic transaminase (GOT), and total proteins, decreased renal activities LDH and GOT and increased concentration in kidney tissue of Cd, Cu, and Zn, Cadmium also increased serum BOT and glutamic pyruvic transaminase (GPT), decreased hepatic activities of GOT and GPT, and increased hepatic levels of Cd and Zn. The supplementation of vitamin B-complex (10 mg per kg, orally) simultaneously with Cd caused less marked biological alterations. Cadmium concentration in renal tissue was significantly less on the eighth day whereas the hepatic level of Cd was unaffected by vitamin supplementation. The protective effect of vitamin B-complex in Cd toxicity may be attributed to the interference by the constituents of vitamin B-complex in body absorption of Cd, possibly through forming readily excretable complexes. The results suggest that Cd toxicity can be reduced by vitamin B-complex supplementation.

Is lead exposure the principal cause of essential hypertension?

Lead is a ubiquitous toxin, known to have adverse effects on the body even at low levels of exposure. In this review we explore whether low lead may be the principal or a major contributory cause of essential hypertension, and whether removal of lead from the environment may eventually reduce both the overall incidence of hypertension and the increased incidence with aging.

Kinetics of nickel binding in hepatic and renal cytosol of(63)NiCl 2-treated rats.

Elution profiles of nickel-binding protein were investigated in hepatic and renal cytosol of rats at various time intervals (6, 16, 24, and 48 h) after intraperitoneal administration of(63)Ni (1 mg Ni/kg. B. Wt. = 400 µCi as(63)NiCl2). The nickel-binding proteins were characterized in terms of absorbance at 254 nm, sulfhydryl content, and(63)Ni counts. The results demonstrated that in liver it was bound to both high as well as low mol wt sulfhydryl proteins and glutathione-like moiety with a maximum incorporation at 16 h, after which it declined and by 48 h, very little(63)Ni was associated with the bioligands. In kidney the incorporation of(63)Ni was approximately 400-fold higher than liver and most of(63)Ni was associated with the low mol. wt. sulfhydryl moiety. Kidney also exhibited maximum incorporation of(63)Ni at 16 h that was metabolized by 48 h.

Galactosylated liposomes as carriers for targeting meso-2,3-dimercaptosuccinic acid to cadmium storage sites in cadmium exposed mice.

In this study an attempt has been made to examine the efficacy of meso-2,3-dimercaptosuccinic acid (DMSA) using galactosylated liposomes as carriers for mobilization of cadmium from the body of mice preexposed to cadmium chloride (0.005 mmoles/kg intraperitoneally daily for 4 days). Cadmium-exposed mice after a rest period of 8 weeks were administered DMSA intravenously, two injections 15 micromoles/kg with an interval of 48 h, as free form of DMSA, or DMSA encapsulated in liposomes composed of phosphatidyl choline, cholesterol and phosphatidyl ethanolamine (7:2:1; PC-lip-DMSA) or in liposomes to which p-aminophenyl galactoside had been anchored (Gal-lip-DMSA). Excretion of cadmium through urine and feces was monitored for 5 days. Thereafter animals were sacrificed, liver, kidneys, spleen and isolated hepatocytes were analysed for cadmium, copper and zinc concentration. Efficacy for cadmium mobilization from the body was found to be in the order Gal-lip-DMSA>PC-lip-DMSA>DMSA. These results show that liposomes can be used as targeted carrier system for chelating agents safely and efficiently as compared to administration of free chelating agent.

Influence of size of liposomes in potentiating the efficacy of encapsulated triethylenetetramine-hexaacetic acid (TTHA) against cadmium intoxication.

Polyaminocarboxylic acids have widely been used an antidotes in heavy metal intoxication, however their hydrophilic nature renders them to be mostly distributed extracellularly. To facilitate the intracellular delivery of such chelating agent, triethlenetetraamine-hexaacetic acid (TTHA) was encapsulated in small unilamellar vesicles (SUV) or dehydration rehydration vesicles (DRV) and its effect was examined in the amelioration of cadmium toxicity. Mice were administered cadmium (0.2 mg/kg B.wt.) as CdCl2 intraperitoneally daily for five days. After a period of four weeks rest. they were given two intravenous injections of TTHA as free material or encapsulated in liposomes (0.16 m mole/kg) at a gap of 48 hours. Urinary and fecal elimination of cadmium and its distribution in the liver, kidney and spleen was monitored after TTHA treatment. The results indicate the efficacy of TTHA in removing cadmium from the body organs of preexposed animals and its excretion through urine and feces was maximum when it was encapsulated in SUV liposomes.

Cadmium-mediated induction of cellular defence mechanism: a novel example for the development of adaptive response against a toxicant.

Early response to the exposure of cadmium includes the enhancement in lipid peroxidation with the concomitant impairment in antioxidative defence mechanism. This investigation deals with the delayed response of cadmium induced stimulation of endogenous defence response against its oxidative damage. The administration of cadmium led to an increase in the hepatic enzymatic and nonenzymatic defence armory in a dose dependent manner 72 hrs post its administration. This includes respectively an increase in the activities of superoxide dismutase, glutathione peroxidase, glucose-6-phosphate dehydrogenase and in the levels of glutathione, metallothionein and zinc. Cadmium administration also stimulated serum ceruloplasmin activity in a dose dependent manner. These changes are accompanied by the concomitant decrease in the peroxidative damage to lipids. Our results suggest the development of a delayed adaptive/defence response as a result of exposure to cadmium.

Efficacy of liposome encapsulated triethylenetetraamine hexaacetic acid (TTHA) against cadmium intoxication: role of lipid composition.

Efficacy of Triethylenetetraamine hexaacetic acid (TTHA) encapsulated in liposomes having different lipid compositions was examined in animals pre-exposed to cadmium. Mice were injected with cadmium as cadmium (II) chloride 0.5 mg/kg b. wt. intraperitoneally daily for five days. Four weeks after the last injection of cadmium they were administered three injections of TTHA encapsulated in liposomes composed of either phosphatidyl choline:cholesterol (PC:Chol) or sphingomyelin:cholesterol (SM:Chol) in 1:1 molar ratio at a gap of 48 h. Urinary and fecal elimination of cadmium and its distribution in liver, kidneys and spleen were examined. Treatment with TTHA encapsulated in liposomes mobilized higher amount of cadmium from liver and spleen. The overall efficiency for cadmium mobilization was better in TTHA encapsulated in SM:Chol liposome treated group which also led to enhanced excretion of cadmium through urine and feces. The results indicate that TTHA encapsulated in SM:Chol liposomes exhibited highest efficacy in mobilizing cadmium from the body of pre-exposed mice followed by PC:Chol liposomes and the free drug.

Exacerbation of nickel induced oxidative response by vitamin E.

Vitamin E (alpha-tocopherol), a well known naturally occurring chain breaking antioxidant and a free radical scavenger was found to exacerbate nickel (Ni) toxicity in mice. Vitamin E (Vit. E) mediated enhancement of nickel toxicity was demonstrated by (i) enhanced mortality in mice treated with Ni and Vit. E (ii) increased hepatic lipid peroxidation, (iii) increased rate of benzoate hydroxylation, and (iv) liposomal membrane damage.

Effect of liposome-encapsulated meso-2,3-dimercaptosuccinic acid on mice exposed to lead through drinking water.

Liposomes are the potent carriers of therapeutic drugs for their targeted delivery to the intracellular sites specially when the drug is hydrophilic in nature and is unable to cross the cell membrane. Lead, a major source of environmental pollution, is accumulated in the body system of both animals and humans through reticuloendothelial system, the site where liposomes also get engulfed upon their entry into the body. In view of these considerations, meso-2,3 dimercaptosuccinic acid (DMSA), a potent chelating drug used in heavy metals intoxication, specially lead, was encapsulated in small unilamellar liposomes composed of phosphatidyl-choline and cholesterol (1:1) and used to evaluate its efficacy in lead intoxication. DMSA either in free form or encapsulated in liposomes was administered intravenously (2,62 mumoles/kg, three injections at a gap of 48 hours each, total 7.85 mumoles/kg) to mice which were pre-fed with lead in drinking water (500 micrograms/ml) for one month. It was found that only DMSA encapsulated in liposomes was significantly effective in reducing the level of lead in liver, kidneys and spleen at the dose administered. DMSA either in free form or encapsulated in liposomes also restored the inhibition in blood delta-aminolevulinic acid dehydratase (delta-ALAD) activity. The results suggest that liposome encapsulated DMSA may be preferred over free DMSA for reducing the body burden of lead.