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February 2002

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Toxicology of Traditional Remedies

Dr Vanessa Steenkamp, Wits University

Traditional remedies are very much a part of African cultural heritage, and very much a part of modern day practices. While many traditional remedies may be of benefit, some may have little or no effect, and others may have the exact opposite effect. Important steps are being taken to find common ground between traditional remedies and so-called Western science. Increasingly we are seeing traditional remedies becoming available in Western health care shops. It is simply a trip down to a street vendor to get a cure for stomach cramps, swollen feet or nausea. A traditional healer has a vast array of cures for a vast array of ailments and not necessarily for health - a jilted lover may find something to bring his or her partner back or someone may be in need of a protection from an evil spirit. But what happens if the cure is toxic? This is where modern day scientific and health care methods must and can step in.  Dr Vanessa Steenkamp of Wits University has this account to offer of toxicology as it relates to traditional remedies.

 

Clinicians in the developed West have now settled into an environment in which they are able to address the problems in most cases of poisoning in a logical fashion. In the developing world the situation is far from clear. In many countries, including South Africa, the majority of the population resort to traditional remedies in the first instance. The composition of many of these remedies are completely unknown. Traditional remedies or muti may be prescribed on the basis of colour. Some remedies are effective, others are harmless, but a number of others have considerable toxicity, especially when administered to small children. Patients who are poisoned present often to rural hospitals and clinics where there are not the facilities to identify the toxin. By the time the patient, or a specimen of urine, reaches a tertiary laboratory, there is often no detectable toxin or metabolite.

Toxicological Cyles

The toxicological cycle below indicates the steps through which the study of a particular human toxin has to pass before the laboratory and the clinician can address effectively the treatment of patients poisoned with that substance. Toxciology Cycles

The toxicology cycle has been completed for a number of toxins such as paracetamol, organophosphorus pesticides, salicylate, tropane alkaloids, morphine, iron, etc., but there remain many poisons for which the cycle is incomplete in that, although the laboratory can assist with diagnosis and prognosis, there is no specific effective treatment available e.g. paraquat.

Since in most cases the toxin is unknown, there is a real need for screening procedures which can be used in such cases. Unfortunately, although TLC (e.g. the TOXILAB™ system), HPLC (e.g. REMEDI ™) and GC/MS screening methods can detect these toxins, the dictionaries, with a few exceptions, cannot assist with identification. The exceptions are those remedies which contain cardiac glycosides, tropane or pyrrolizidine alkaloids. We now have HPLC/LDA traces on over 100 traditional herbal remedies, but in only a fraction of these are there peaks which we can positively identify. 

Thankfully the botanists are well ahead and there is a need for a synthesis of knowledge in this area. We now resort to the use of two simple screening tests, one of which detects alkaloids (not necessarily toxic)(1) and the other the specifically toxic pyrrolizidines which give rise to veno-occlusive liver disease (2). We also are able to detect the hepatotoxic compound atractyloside, a component of the remedy Impila using TLC with anisaldehyde as a detection reagent (3). Thereafter we employ HPLC with linear diode array or GC/MS to probe further (4).

Apart from herbal remedies, a vast array of soils, metal salts and animal parts are used as remedies. The latter do not concern us in Africa from an analytical point of view since few are toxic, although they may present infection risks. However in other areas of the world animal toxins from fish, snakes and frogs predominate and offer the same analytical problems. We do, however, see many cases of poisoning with metals, a number of which progress to renal failure and death. Since these powders are not easy to identify, a broad spectrum analytical technique is required and we now use ICP OES for these studies. By and large African traditional herbal remedies do not contain high levels of metals (5), but mixed remedies may be almost pure metal salt, examples being copper sulphate and potassium dichromate, which may be used as enemas with disastrous effects.

What are the requirements for the development of useful toxicological procedures in developing countries? Firstly, clinicians must be trained to obtain the first available urine specimen from a suspected case of poisoning and to collect also any available muti which has been taken. This may not be easy since there is a great deal of fear of the traditional healers and the remedies may be disposed of if the doctor shows too much interest. Secondly, there is a need for prospective research on screening methods. Thirdly, specific methods for the most common toxins are required. The problem is that the drive for increased specificity of tests in the West has paradoxically left us without the required tools. A non-specific digoxin immunoassay can be used to detect e.g. oleandrin, a common poison in this country. However all of the easily available digoxin immunoassays have now such high specificity that they are useless in the screening role. There is a similar requirement for non-specific immunoassays for other groups of toxins. 

Although we can now detect pyrrolizidines and atractyloside in biological fluids by GC/MS, this is not helpful in a country in which the majority of the laboratories are small and equipped only with analysers such as the Cobas MIRA. The answer is a panel of non-specific optical immunoassays, such as are now widely available for drugs of abuse, which can be used on these analysers to give a positive or negative response. The only other technique which could be made available at the point of care is the TOXILAB™ system and here we are currently investigating its usefulness in our environment. As with all other major challenges in Clinical Chemistry, the toxicology of traditional remedies is going to require not only the efforts of small pioneer units such as ourselves, but the active participation of our commercial colleagues. The carrot will be that these remedies are increasingly in use in our Western cities due to importation from the countries of origin. Secondly, it should be remembered that these remedies are seldom specific to one country and that there are cases documented throughout the developing world. The market is small at present due to lack of education. One move in the right direction is the training course on the detection of traditional remedies held in Hong Kong in March of this year. Such efforts should be increased in order to widen the current scattered efforts, with the aim of providing global screening and specific detection methods to aid clinicians presented with these very difficult problems.

More Information

1. Birecka H, Catalfamo J, Eisen R. A sensitive method for the detection and quantitative determination of pyrrolizidine alkaloids. Phytochemistry 1981;20:343-4.
2. Mattocks A. Spectrophotometric determination of pyrrolizidine alkaloids- some improvements. Anal Chem 1968;40:1749-50.
3. Steenkamp V, Stewart M, Zuckerman M. Detection of poisoning by Impila (Callilepis laureola) in a mother and child. Hum Exp Toxicol 1999;18(10):594-7.
4. Laurens T, Bekker L, Steenkamp V, Stewart M. Gas chromatographic-mass spectrophotometric confirmation of atractyloside in a patient poisoned with Callilepis laureola. J Chromatogr (B) 2001;765:127-33.
5. Steenkamp V, von Arb M, Stewart M. Metal concentrations in plants and urine from patients treated with South African traditional remedies. 2000;114:89-95.

Should anyone be interested in a research project or collaboration to
contact
Dr Vanessa Steenkamp (011) 489 8514
or
Prof Mike Stewart (011) 489 8551
Address: Indigenous Toxicology Unit
Dept of Chemical Pathology
University of the Witwatersrand Medical School
7 York Road
Parktown
Johannesburg
2193






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