Hepatotoxic plants

Oshima Y, Namao K, Kamijou A, Matsuoka S, Nakano M, Terao K, Ohizumi Y (1995) Powerful hepatoprotective and hepatotoxic plant oligostilbenes, isolated from the oriental medicinal plant Vitis coignetiae (vitaceae). Experientia 51 63-66... 

Toxicity. Consumption of hepatotoxic plants that coinckies with the intake of significaiit... 

We knew Utetheisa to feed on poisonous plants as a larva (Figure 1B). The plants, of the genus Crotalaria (family Leguminosae), were known to contain pyrrolizidine alkaloids (henceforth abbreviated as PAs), intensely bitter compounds potently hepatotoxic to mammals (7). Other species of Utetheisa were known to sequester PAs (8). We found this to be true for U. ornatrix as well. Adult Utetheisa raised on Crotalaria spectabilis, one of the principal foodplants available to the moth in the United States, contain on average about 700 p,g of monocrotaline (1), the principal PA in that plant (9, 10). 

The best evidences are studies from preclinical animal models [86, 87, 105], or knockout animals lacking appropriate anti-oxidative pathways [106]. For example, Balb/c mice administered a variety of anti-oxidants in their chow were protected from acetaminophen hepatotoxicity [107]. Rats fed with the anti-oxidant melatonin were protected from cholesterol mediated oxidative liver damage [108]. The best clinical evidence that oxidative stress is a key player in a variety of liver injury diseases is the beneficial application of silymarin in these disease indications [109]. Silymarin is a polyphenolic plant fiavonoid (a mixture of flavonoid isomers such as silibinin, isosilibinin, silidianin and silichristin) derived from Silymarin maria-num that has antioxidative, antilipid peroxidative, antifibrotic and anti-inflammatory effects [109, 110]. 

Gene expression inhibition. Chloroform/ methanol extract (1 1) of the dried leaf, in cell culture, was active on hepatoma-Cos-7, IC50 600.0 pg/mL vs TAT-dependent activation of HIV promoter hioassay - . Hepatotoxic activity. The leaf, taken orally by a female adult, was active - . A patient consumed 15 tablets of the leaf per day for 4 months. Approximately 1 year after stopping consumption, liver enzymes returned to normal and fatigue was no longer a complaint - ". Infusion of the dried leaf, taken orally by a female adult at variable doses, was active. The 60-year-old woman who took Lama tridentata for 10 months developed severe hepatitis for which no other cause could be found. Despite aggressive supportive therapy, the patient s condition deteriorated and required orthotropic liver transplantation - " . Dried leaves, administered orally to adults at variable doses, were active. A public warning has been issued by the US Centers for Disease Control based on reports of liver toxicity after use of Lama tridentata tea - " k Dried leaves, administered orally to adults of both sexes at variable doses, were active - ". The plant, administered orally to adults at variable doses, was active - ". Dried leaves, administered orally to adults at variable doses, were active. One case of hepatotoxicity induced by Larrea tridentata taken as a nutritional supplement was reported - ". Thirteen patients were identified for whom Larrea tridentata tincture for internal use was prescribed. Additionally, 20 female and three male patients were identified from whom an extract of Larrea tridentata in castor oil for... 

Coltsfoot Upper respiratory tract infections Pyrrolizidine alkaloids, hepatotoxicity Avoid ingestion of any parts of plant leaves may be used topically for anti-inflammatory effects for up to 4-6 weeks... 

Russian comfrey (Symphytum x uplandicum Nyman) is widely recommended as a medicinal herb and an item of human diet. A previous investigation of this species led to the isolation of three alkaloids which were not fully characterized (cf. Vol. 7, p. 57). Culvenor and co-workers have separated eight pyrrolizidine alkaloids from the leaves of this perennial plant by counter-current distribution.21 The known alkaloids echimidine (51), symphytine (52), lycopsamine (53), and intermedine (54) were present. In addition, four new alkaloids, i.e. 7-acetyl-lycopsamine (55), 7-acetylintermedine (56), symlandine (57), and uplandicine (58), were characterized by spectroscopic methods, and by hydrolysis. The total alkaloidal extract caused chronic hepatotoxic effects in rats, and the authors... 

Pyrrolizidine alkaloids (PAs) are a typical class of plant secondary metabolites, which certain butterflies and moths in particular groups, that is, Danainae, Ithomiinae (Nymphalidae), and Arctiidae, sequester as larvae or adults and utilize as chemical defensive substances against predatory enemies, probably due to their bitter taste and hepatotoxicity.13 PAs also serve as precursors of male pheromones of PA-storing lepidopterans. 

Alkaloids that contain pyrrolidine and pyrrolizidine ring systems are derived from the nonprotein amino acid, L-ornithine. Cocaine (Nl) and (—)-hyoscyamine, the two important pyrrolidine alkaloids that contain a tropane ring system, have been found to occur in coca (Erythroxylon coca, Erythroxylaceae) leaves and the whole plant of the deadly nightshade (Atropa belladonna, Solanaceae). The hepatotoxic alkaloid senecionine (N2) contains a bicyclic pyrrolizidine skeleton derived from two molecules of L-ornithine. 

Hepatotoxic, e.g. from Amanita phalloides (death cap mushroom), from Senecio (ragwort) and Crotalatia and from bush teas prepared from these plants in the Caribbean. Aflatoxin, from Aspergillus flavus, a fungus which contaminates foods, is probably a cause of primary liver cancer. 

It is difficult to clarify the hepatotoxicity of herbal remedies, especially if they are comprised of a mixture of several plants or various components of the plant. Moreover, herbal remedies are often applied as automedication, and patients withhold the information that they have used them. (s. tab. 29.9) (s. fig. 29.15)... 

Tab. 29.9 Medicinal plants with reported or suspected facultative hepatotoxicity (ALF = acute liver failure, R = rare) (with some references)...

Information about the effectiveness or safety of herbal remedies is based on experience transmitted over centuries rather than on controlled trials or toxicity studies. Numerous medicinal plants have been reported to possess facultative hepatotoxicity, or there is suspicion thereof (53, 72, 76, 90, 108, 109)... 

Kaplowitz, N. Hepatotoxicity of herbal remedies insights into the intricacies of plant-animal warfare and cell death. Gastroenterology 1997 113 1408-1412... 

Many species of Senecio, such as Senecio jacobaea (ragwort) and Senecio longilobus (thread leaf groundsel), contain hepatotoxic amounts of pyrrolizidine alkaloids (which are covered in a separate monograph). Honey made from Senecio plants also contains pjrrolizidine alkaloids (32). 

The diseases induced by LPO involve arteriosclerosis, diabetes mellitus, halotane hepatotoxicity and liver desease. Some antioxidants and scavengers inhibit peroxidation induced by ROS (i.e., a-tocopherol, glutathione and carotenoids). Recently, natural oxidants have been found from many plants, such as spices, vegatables and herbs [276]. Kaempferol and quercetin as flavonols scavenge ROS and inhibit LPO. 

Flowever, ampelopsin C and the mixture of (-i-)-vitisin A (698) and (+)-cw-vitisin A (702) were found to be powerful hepatotoxins. The coexistence of hepatoprotective and hepatotoxic agents in the same plant is very interesting, and the plant has been used to cure hepatic diseases such as hepatitis and liver cirrhosis [519]. 

Many chemicals are hepatotoxic, including thousands of synthetic drugs and chemicals as well as a plethora of natural compounds such as bacterial, fungal, plant, and animal toxins. Some examples of chemicals causing liver injury are shown in Table 2. 

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