Severe Toxic Hepatitis Provoked by Squeezed Black Radish (Raphanus Sativus) Juice - Case Report

Zoran Joksimović (1), Dušan Bastać (2)
(1) Internistička ordinacija "Joksimović" Bor, (2) Internistička ordinacija "Dr Bastać" Zaječar

INTRODUCTION

A large number of approved medicines by official pharmacopoeia as well as alternative healing medicines and herbal medicines, could provoke toxic hepatitis. Lately, a term ‘herbal related toxic hepatitis’ has appeared in literature because there are more and more cases of toxic liver damage caused by the use of herbal medicines and their preparations and final medicines based on plants [1]. However, it is considered in everyday practice that those medicines could not provoke harmful effects and we recognize them very rarely as etiological factors of many unexplained cases of liver damage. For these reasons, but also due to the fact that patients sometimes take many medicines at the same time, diagnosis setting on herbal hepatotoxity could be very difficult.
According to the type of lesions provoked by herbal medicines, there are parenchymic and cholestasic forms of hepatitis. There, the agents with toxic effect cause, first of all, parenchymic damage, and those ones with hypersensitive effect the cholestasic form of hepatitis. It is possible that the same agent has effect in two ways [2]. Hepatotoxic substances or their metabolites damage hepatocytes directly resulting into necrosis or damage the cell integrity such as by provoking “self-destruction” that is programmed cell death apoptosis [3].
The liver has great importance in the metabolism of medicines including herbal medicines, and hepatocytes are exposed to concentrations of newly-formed metabolites that are formed in reactions of medicine oxidation with participation of cytochrome P450 enzyme. Chemically reactive metabolites could form incovalent bonds with the aimed molecules or change the aimed molecule by covalent interactions, and both reactions are possible at the same time. Potential cytotoxic incovalent reactions are lipid peroxidation, generation of toxic radicals, discharging of glutathione level, modification of sulphydril groups. Lipid peroxidation of polysaturated fats could be started by reactive metabolite or reactive oxygen radicals formed by such metabolites. Lipid peroxiradicals by chain reaction over peroxide cascade include much more lipids in membrane and provoke cell damage and finally its death. If protective mechanisms, as well as glutathione peroxidase and vitamin E, are not included enough and on time, lipid peroxidation will not be enough to result into cell necrosis. But generation of toxic cell radicals could result into cytotoxicity. Toxic radicals are formed by reduction of molecular oxygen to superoxide anions, and then by enzymic conversion to hydrogen peroxide or reactive free radicals as well as hydroperoxide and hydroxyl radicals and the so called singlet oxygen. Those reactive oxygen radicals are cytotoxic over lipid peroxidation, too. “Oxidative stress” is formed by reactions that cause depletion of glutathione level, which is the result of balance disturbance between peroxidants and antioxidants in cells in favour of prooxidant conditions. Oxidoreductive cycle of glutathione (GSH) that is normally in a couple with glutathione disulphide (GSSG), presents a protective mechanism that decreases damage of cells due to oxidative stress. Free oxygen radicals transform GSH into GSSG (where GSH is regenerated under the influence of GSSG reductase with activity depending on NAADPH). If a drop of GSSH level appears for 20 – 30%, the defensive cell system will be disturbed and a death of cell can appear.
Modification of sulphydril groups could be formed by action of free oxygen radicals that change reversibly sulphydril group or covalent interaction. Free sulphydril group has a crucial importance for catalytic activity of many enzymes, and their modification results into inactivation of enzymes. Inactivation of enzymes results into increased Ca concentration of cell, which causes the death of cell.
Covalent interactions result into changes on proteins to become immunogenous, and DNK changes result into mutagenes responsible for carcinogenesis and teratogenesis [2].
For treatment of cholecystolithiasis, people use medicaments for gallstone ejecting and melting. For the aim of gallstone melting in the bile duct, the medicaments based on black radish juice and in combination with other plants or “healing” medicines are very favorable. Therefore, black radish in a large number of handbooks and instructions in the field of phytotherapy, homeopathy and self-treatment is a very powerful hepatoprotective and well-known healing medicine in the treatment of liver disorders and bile ducts. There are a large number of internet sites on healing effects of black radish on liver and bile ducts, and there are also a number of forums on the topic: “Does black radish melt gallstones in bile ducts?”
Also, in medical expert literature, the black radish juice has proved antioxidant features, although the mechanism of biological active components of black radish on lipid peroxidation is not completely clear [5]. It was established that the black radish extract decreases the level of lipid peroxidation and this effect depends on juice concentration [6]. It was shown that antiflamatory and antiapoptosic features of black radish have a hepatoprotective activity.
In an experiment with rabbits with cadmium (Cd) provoked liver damage, a significant decrease of the total level of liver bilirubins and enzymes resulted in rabbits fed with powder of dried black radish [7]. The effect of black radish root is also favourable on the structure and redox system status of colon mucosa of mice. After a rich fat diet, the mice had inflammation and lesion of enetrocyte. After nutrition with black radish granulates, the results were similar as the ones with mice in the control group that were on balanced nutrition. The colon mucosa was better – the cells like cup were increased and inflammation was removed [8]. In recommendation for diet in prevention of carcinoma of gall bladder, the use of black radish decreases significantly the risk for this organ carcinoma [9], which is possible due to the fact that one isocyanate-sulphoraphen, isolated from black radish “in vitro” shows the activity of mutagenous inhibition [10].
Black radish belongs to the order of cruciferous plants. It is consider that the origin of this plant is in Asia and there are some assumptions that it originated from a wild radish. Nowadays there is no wild radish in nature. It is known that the ancient Egyptians made oil from wild radish seed. In the ancient Greek and Roman, the healing characteristics of radish were known also in treatment of respiratory organs. The radish was mentioned in France during the renaissance period, when the effect of black radish was specially used for bile secretion [11]. This rooty plant in a form of beet has black surface and white fleshy root. It has extremely hot taste. When it is used in raw condition, it usually causes flatulence in the stomach. Black radish is not mainly used as nutrient, but as addition to food (mainly salads) or as a diet-healing ingredient of food. It is reach with C vitamin and has antioxidative characteristics. As regards minerals, it is reach in potassium. Due to the content of many plant fibres and certainly also water – that increases the transit of stool through the intestine, it is recommended in nutrition of patients with constipation. It is considered that some ingredients of black radish improve discharging of gall bladder and bile vessels and therefore it is recommended in common medicine to the patients with hepatobilliary system diseases. Due to antibacterial effects, it is also used by patients with disorders of intestinal flora. Ethereal oils of black radish are secreted over mucosa of the respiratory system, so this plant is also used in the treatment of cough [12].

CASE REPORT

Thirty year-old patient Z.G. from Podgorica. For a couple of last years she knows about having the stones in the bile duct. She has periodically the undetermined pains under the right rib arch. She has heard from friends that black radish is efficient in melting of bile stones and starts “a therapy with black radish juice”.
She drinks 150 ml of black radish juice two times every day. She squeezes juice in a juicer and for daily dose of 300 ml juice, she mills and squeezes about 900 gr of raw black radish. The juice has a repulsive extremely hot taste and unpleasant smell. Upon consumption of each dose she has burning in the stomach and indescribable feeling of nausea followed with shaking and perspiration as well as frequent mushy stools.
The patient continues persistently with taking of juice thinking that “it should be” and that it is exactly “the healing effect” of juice. When, after a month and a half of medicament application she has spent a sack of 50 kg of black radish, she herself requires a control of laboratory parameters due to nausea and burning in the stomach, the personnel in the laboratory checks twice the level of liver enzymes because they are surprised with the high level of AST (710) and ALT (1130).
The patient reports for medical examination on 17.03.2007. At the acceptance, she is afebrile, eupnoic, anirectal cardiopulmonal compensated. Physical findings of the lungs and the heart are normal. TA 115/70. The stomach is palpatory painful sensitive under the right rib arch. The liver is palpitated on the edge d.r.1 at deep expirium. The spleen is not touchable. Pathological resitencies are not palpitated.
We present Table 1 with the values of enzymes per dates.
All the other laboratory findings, including red and white blood picture, bilirubins, alkaline phosphatase, gamma GT, fibrinogen, electrolytes, Fe, glycaemia and lipid status, are many times controlled and they are always within the limits of reference values.
Markers for viral hepatitis A, B and HIV are negative. ECHO of the upper abdomen:
Gall bladder with thickened wall, partially filled lumen with a large number of concrements, diameter up to 8 mm. Liver, spleen, pancreas and kidneys without noticeable echonoscopic changes.
Esophagogastroduodenoscopy: duodenogastritic biliary reflux without noticeable changes at the level of mucosa.
Colonoscopy: normal endoscopic findings.
CT of abdomen shows lightly diffuse swollen liver and normal other solid organs.
We advise hospitalization to the patient which she refuses due to the family reasons and we conduct medical treatment in home conditions. That means immediate interruption of the “therapy” with black radish. We determine a peroral diet to the patient without animal fat, reached with vitamins and we practice the supported therapy with amino acid infusion solutions (Amino and Hepasteril). After 10 days, we exclude the infusion solutions and we peroraly add the amino acid drugs (Essentiale), and when the enzymes are normalized, we exclude every form of medical therapy. The patient is under everyday medical supervision, and the laboratory analyses are controlled every 2-3 days at the beginning and later rarely. Subjective discomforts have been removed after only two days of interruption of taking the black radish juice, and laboratory analyses show gradually continuous decrease of liver enzyme level. We also control the other biochemical parameters that are not over the normal values during the treatment. After interruption of medical therapy, the patient is still on a diet without animal fat. After two months, liver enzyme levels are completely normalised.
Table 1 presents a review of liver enzyme levels per dates. Figurative presentation of the data is also presented in Graph 1 in the attachment.

TABLE 1 Review of enzymes per dates

DISCUSSION

A number of herbal drugs were described that could result in enormous increase of liver enzymes such as noni [13], coffea-coffea, gingseng, ehinacea, ginkgo biloba, centarium umbellatum.
It was shown that many herbal drugs, mainly from the assortment of Chinese traditional medicine, Japanese kampo medicine and Indian ajurveda medicine could cause liver lesions [14, 15].
Hepatotoxic effect of herbal drugs is caused by the effect of various toxic substances or drug overdosing or combination with other (un)toxic substances [16].
Contrary to the widespread belief that herbal drugs are a priori safe and not dangerous, we have presented the case of severe toxic hepatitis provoked by the use of wider herbal drug that is an excellent hepatoprotective.
As we have not found any described examples of distinctive hepatotoxity of black radish in literature and data sources, we think that is interesting to present such a case.

CONCLUSION

This work presents toxic hepatitis provoked by the use of squeezed black radish. Black radish is considered as one of the best hepatotprotectives in folk medicine and phytotherapy, and it was the use of squeezed black radish that resulted into severe toxic hepatitis. Again, the validity of famous Paracelsus declaration is confirmed: “Nihil venenum est et omnia venenum; quod interest portio est” (“Nothing is poison and everything is poison; the difference is in dosage”).
Interruption of the “therapy”, diet and usage of infusion of amino acid solutions had a more favourable result. After two months, there is a completely normalised liver function (restitutio ad integrum).
Although it looks anachronous, it can be concluded that it is still necessary to work on the increase of health culture of people and similar incidents could thus be avoided.

REFERENCES

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