The use of and search for drugs and dietary supplements derived from plants have accelerated in recent years. Ethnopharmacologists, botanists, microbiologists, and natural-products chemists are combing the Earth for phytochemicals and “leads” which could be developed for treatment of infectious diseases. While 25 to 50% of current pharmaceuticals are derived from plants, none are used as antimicrobials. Traditional healers have long used plants to prevent or cure infectious conditions; Western medicine is trying to duplicate their successes. Plants are rich in a wide variety of secondary metabolites, such as tannins, terpenoids, alkaloids, and flavonoids, which have been found in vitro to have antimicrobial properties. This review attempts to summarize the current status of botanical screening efforts, as well as in vivo studies of their effectiveness and toxicity. The structure and antimicrobial properties of phytochemicals are also addressed. Since many of these compounds are currently available as unregulated botanical preparations and their use by the public is increasing rapidly, clinicians need to consider the consequences of patients self-medicating with these preparations.

Plant Products as Antimicrobial Agents

Gout

ContextLead, mercury, and arsenic intoxication have been associated with the
use of Ayurvedic herbal medicine product (HMPs).ObjectivesTo determine the prevalence and concentration of heavy metals in Ayurvedic
HMPs manufactured in South Asia and sold in Boston-area stores and to compare
estimated daily metal ingestion with regulatory standards.Design and SettingSystematic search strategy to identify all stores 20 miles or less from
Boston City Hall that sold Ayurvedic HMPs from South Asia by searching online
Yellow Pages using the categories markets, supermarkets, and convenience stores, and business names containing the word India,
Indian cities, and Indian words. An online national directory of Indian grocery
stores, a South Asian community business directory, and a newspaper were also
searched. We visited each store and purchased all unique Ayurvedic HMPs between
April 25 and October 24, 2003.Main Outcome MeasuresConcentrations (μg/g) of lead, mercury, and arsenic in each HMP
as measured by x-ray fluorescence spectroscopy. Estimates of daily metal ingestion
for adults and children estimated using manufacturers’ dosage recommendations
with comparisons to US Pharmacopeia and US Environmental Protection
Agency regulatory standards.ResultsA total of 14 (20%) of 70 HMPs (95% confidence interval, 11%-31%) contained
heavy metals: lead (n = 13; median concentration, 40 μg/g; range,
5-37 000), mercury (n = 6; median concentration, 20 225
μg/g; range, 28-104 000), and/or arsenic (n = 6; median
concentration, 430 μg/g; range, 37-8130). If taken as recommended by the
manufacturers, each of these 14 could result in heavy metal intakes above
published regulatory standards.ConclusionsOne of 5 Ayurvedic HMPs produced in South Asia and available in Boston
South Asian grocery stores contains potentially harmful levels of lead, mercury,
and/or arsenic. Users of Ayurvedic medicine may be at risk for heavy metal
toxicity, and testing of Ayurvedic HMPs for toxic heavy metals should be mandatory.

Heavy Metal Content of Ayurvedic Herbal Medicine Products

Toxic heavy metals and undeclared drugs in Asian herbal medicines

Occupational and environmental exposures to lead (Pb), one of the toxic metal pollutants, is of global concern. Health risks are increasingly associated with environmental exposures to Pb emissions from, for example, the widespread use of leaded gasoline in developing countries. Exposure occurs mainly through the respiratory and gastrointestinal systems, and the ingested and absorbed Pb is stored primarily in soft tissues and bone. Autopsy studies of Pb-exposed patients have shown a large amount (approximately 33%) of the absorbed Pb in soft tissue stored in liver. In addition to neuronal encephalopathy observed in persons after exposure to very high concentrations of Pb, gastrointestinal colic (abdominal pain, constipation, intestinal paralysis) is a consistent early symptom of Pb poisoning in humans. Such severe gastrointestinal effects are consistently observed in patients with a blood Pb range of 30 to 80 microg/dl. Ingestion of Pb is one of the primary causes of its hepatotoxic effects. Hepatocarcinogenic effects of Pb reported in animal toxicology studies have led to new research into the biochemical and molecular aspects of Pb toxicology. Gains in the molecular understanding of Pb effects on hepatic drug metabolizing enzymes, cholesterol metabolism, oxidative stress, and hepatic hyperplasia suggest a potential role for Pb in damaging extrahepatic systems, including the cardiovascular system. This review also discusses the therapeutic potential of chelation therapy in treating Pb-induced hepatotoxicity in animals.

Lead hepatotoxicity & potential health effects.

Objective: The aim of this study was to confirm the connection between lead poisoning and the use of traditional Ayurvedic metal mineral tonics. Methods: The study group comprised 29 subjects (26 adults and three children) who had previously taken Ayurvedic metal mineral tonics. All subjects were tested for lead absorption by blood lead, erythrocyte δ-aminolevulinic acid dehydratase activity and erythrocyte protoporphyrin. Results: Eighteen samples of Ayurvedic preparations were obtained from 15 subjects and analyzed for lead content. Five adult subjects with established lead poisoning received chelation therapy. In Ayurvedic preparations a wide range of lead content was found (0.9-72,990 μg Pb/g; 0.35-29,900 μg Pb/capsule or tablet). The blood lead, erythrocyte δ-aminolevulinic acid dehydratase and erythrocyte protoporphyrin of the subjects, grouped according to the remedies used, correlated with the lead content in the preparations (p < 0.001). Chelation therapy was successful in normalization of labora...

Lead poisoning associated with the use of Ayurvedic metal-mineral tonics.

The very young are more prone to lead poisoning than adults, and the treatment with chelating agents, either as monotherapy or combined treatment, is still a matter of dispute. The purpose of this work was to evaluate the efficiency of three chelating agents administered either as monotherapies or as combined treatments in sucklings. Lead acetate (5 mg Pb kg−1 i.p.) was administered to the 7-day-old rat pups in eight litters on experimental day 1 and chelating agents on experimental days 2 and 3. Pups were divided into six groups: (1) untreated control; (2) EDTA (calcium disodium ethylendiaminetetraacetate, 0.3 mmol kg−1 i.p. at 4 p.m.); (3) meso-DMSA (meso-2,3-dimeracaptosuccinic acid, 0.5 mmol kg−1 p.o. at 10 a.m.); (4) rac-DMSA (racemic-2,3-dimeracaptosuccinic acid, 0.5 mmol kg−1 p.o. at 10 a.m.); (5) EDTA+meso-DMSA; and (6) EDTA+rac-DMSA. Rats were killed on experimental day 5. Tissue element concentrations were analyzed by atomic absorption spectrometry. Treatment with EDTA did not affect tissue Pb, but it reduced Zn in the carcass and liver. Meso-DMSA reduced Pb in the kidneys and brain, and it did not affect organ essential elements. Rac-DMSA most efficiently reduced Pb concentrations in the carcass, kidneys and brain, but it also reduced Zn and Cu in the liver and Zn in the kidneys. Combined treatments with EDTA never improved the efficiency of either DMSA isoform in decreasing tissue Pb but they did reduce tissue Zn concentrations. All treatments caused the same decrease in the carcass Ca concentrations. The results do not support combined treatment in this age group, which is especially sensitive to trace element deficiencies, and suggest that meso-DMSA might be the treatment of choice in acute lead poisoning in infants. Copyright © 1999 John Wiley & Sons, Ltd.

Combined chelation therapy in reducing tissue lead concentrations in suckling rats.

Subclinical lead poisoning with no clinical symptoms is a dilemma for the occupational health physician. He is supposed to assess when and how to treat workers at risk mainly by the results of biological monitoring. The aim of this study was to demonstrate different responses of biological indices in 50 lead-exposed workers who have been working in the same plant of lead pigment production factory. Twenty-one had normal, that is, permissible blood lead concentrations (PbB), erythrocyte protoporphyrin (EP), and aminolevulinic acid activity (ALAD) measured during regular periodic examinations (group 1). No differences between two measurements were found, although they were continuously working with lead. In 18 of the 50 workers (group 2). PbB and EP concentrations increased, whereas ALAD activity decreased: those parameters improved after a 3- to 6-month cessation of lead exposure. Seven of the 50 workers also had altered values of biological indices, but their condition improved spontaneously without cessation of lead exposure (group 3), while in the remaining four workers, elevated concentrations of biological indices did not change during the observation period. The reasons for such discrepancies and indications for chelation therapy are discussed. Am. J. Ind. Med. 31:631–635, 1997. © 1997 Wiley-Liss, Inc.

Individual variation in response to lead exposure: a dilemma for the occupational health physician.

Abstrat: Racemic dimercaptosuccinic acid (DMSA) was found more efficient than the meso-isoform in enhancing the removal of mercury in rats. However, racemic-DMSA has recently been found more toxic. The efficiency of combined oral treatment with the two isoforms of DMSA for removal of mercury has now been evaluated. Female albino rats were treated orally for four days with meso- (M) and/or racemic- (R) DMSA (1 mmol/kg each), five days after a single intraperitoneal administration of 203 Hg with 0.5 mg HgCl 2 /kg. The animals were divided into six groups according to the number of treatments with each isomer: control (untreated), 4M, 1R+3M, 2R+2M, 3R+1M, and 4R. Whole body, kidney, liver and brain mercury contents were measured nine days after 203 Hg administration. In all treated groups retention in the whole body and kidneys was greatly reduced. The groups treated with racemi-DMSA, regardless of the number of doses, showed a greater removal of mercury than the group treated with meso-DMSA alone (4M). All treatments were less efficient in reducing liver retention, and the brain retention was not affected. It was concluded that even a single application of the more toxic racemic-DMSA during a four-day oral treatment regimen is sufficient to improve the removal by mesoDMSA of mercury from rats.

Combined Oral Treatment with racemic and meso-2,3-Dimercaptosuccinic Acid for Removal of Mercury in Rats

The aim of this study was to evaluate the efficacy of meso-2,3-dimercaptosuccinic acid (DMSA) treatment in workers with increased lead absorption and no overt symptoms of lead poisoning. Seven occupationally lead exposed male workers with blood lead concentrations (PbB) exceeding 50 micrograms/100 ml and a positive calcium disodium ethylenediaminetetraacetate (EDTA) lead mobilization test were treated with DMSA for 19 days. Individual doses were 700 mg DMSA, three times a day from day one to five, and twice a day from day six to 19. The treatment intensified urinary lead excretion, most rapidly during the first five days. The increased elimination was followed by a decline of mean PbB to 15% of the pretreatment values. However, 15 days after the treatment, the PbB concentrations rebounded, yet kept below the baseline values and did not exceed 40 micrograms/100 ml. After repeated EDTA lead mobilization test, urine lead was 23-68% of that before DMSA treatment. It can be concluded that DMSA can effectively reduce chelatable lead in occupationally exposed workers.

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Nada Restek-Samaržija

Papers

Lead poisoning associated with the use of Ayurvedic metal-mineral tonics.

Combined chelation therapy in reducing tissue lead concentrations in suckling rats.

Individual variation in response to lead exposure: a dilemma for the occupational health physician.

Combined Oral Treatment with racemic and meso-2,3-Dimercaptosuccinic Acid for Removal of Mercury in Rats

Meso-2,3-dimercaptosuccinic acid in the treatment of occupationally exposed lead workers