Food toxins and the Caribbean Parkinson plus types.

In the 90's, clinico pathological studies have considerably improved the diagnosis of specific and rare neurodegenerative diseases. After a training in Parkinsons' disease in Paris, the author moved to French West Indies (Guadeloupe) and observed a high incidence of atypical parkinsonism with dementia, unresponsive to levodopa. Similar features were observed in Martinique. An environmental origin has been suspected with the exposure to toxins of annonaceae leaves and seeds. The candidate toxins are acetogenins acting as mitochondrial poison. This was demonstrated in neuronal cell cultures, and in animals. However, the agency for food security did not conclude that Annonaceae should not be used for herbal (medicinal) tea, even if the population is now aware about the possible risk of parkinsonism after exposure to annonaceae acetogenins.

Risk assessment of intake of pyrrolizidine alkaloids from herbal teas and medicines following realistic exposure scenarios.

In this study five types of herbal teas were used to quantify the effect of comminution of the leaves on resulting PA exposure. Results show that PA levels extracted from intact leaves were consistently lower than from comminuted tea leaves. The Margin of Exposure (MOE) approach was applied to evaluate the consequences of this difference for the associated risks in the scenario of lifetime exposure. Furthermore, we considered medicinal use of these teas for shorter-than-lifetime exposure scenarios, and also analysed the risks of shorter-than-lifetime use of eight herbal medicines and 19 previously analysed plant food supplements. This analysis revealed that shorter-than-lifetime use resulted in MOE values < 10,000 upon use for 40-3450 weeks during a lifetime, with for only a limited number of herbal teas and medicines use of two weeks a year (150 weeks during a 75 year lifetime) would still raise a concern. It is concluded that taking more realistic conditions into account markedly reduces the concerns raised for these herbal preparations. These results also illustrate the need for development of a generally accepted method for taking short term exposure into account in risk assessment of compounds that are genotoxic and carcinogenic.

Levels of methyleugenol and eugenol in instant herbal beverages available on the Indonesian market and related risk assessment.

The presence and accompanying risks of methyleugenol and eugenol in herbal beverages available on the Indonesian market were evaluated. Methyleugenol was detected in 49 out of 114 samples, at levels amounting to 2.6-443.7 µg/g, while 4 samples contained eugenol at 21.4-101.2 µg/g. The EDI resulting from drinking these preparations amounted to 0.1-51.2 µg/kg bw/day and 1.1-3.3 µg/kg bw/day, respectively for samples targeted at adults and children. A BMDL10 value of 22.2 mg/kg bw/day for methyleugenol was defined using literature data and model averaging. MOE values were below 10,000 for 46 samples (40.4%), indicating a priority for risk management when assuming daily lifelong consumption, while the EDI for 4 samples containing eugenol did not exceed the ADI of 2.5 mg/kg bw thus did not raise a concern for human health. Using Haber's rule to correct for less than lifetime exposure, consumption of methyleugenol via these beverages would be of low concern when consumed for less than 2 weeks/year during a lifetime. This conclusion holds for herbal beverages collected by targeted sampling, not for all herbal beverages on the Indonesian market. The study provides data that can support establishment of a maximum permitted level (MPL) for methyleugenol in herbal beverages in Indonesia.

Evaluation of Reproductive Toxicology of Aqueous Extract of Yerba Mate (Ilex paraguariensis A. St.-Hil.), a Traditional South American Beverage.

Yerba mate (Ilex paraguariensis A. St.-Hil.; Aquifoliaceae) is a popular tonic and stimulant beverage that is widely consumed in different South American countries. Estimates indicate the consumption of >1 L per day in southern Brazil and Uruguay. Despite its relatively high consumption, data on reproductive toxicity during critical periods of gestation remain unclear. Thus, we evaluated the effects of an aqueous extract of I. paraguariensis leaves ("chimarrão" [IPC]) at two critical periods of gestation in Wistar rats: preimplantation embryonic stage and fetal organogenesis. Pregnant Wistar rats were orally treated with IPC (3, 30, and 300 mg/kg) from days 1 to 7 or 8 to 21 of pregnancy. The respective control groups received vehicle. During treatment, clinical signs of maternal toxicity, maternal body weight, and food and water intake were monitored. The rats were killed on days 8 and 20 of pregnancy, and the following parameters were evaluated: weight of the maternal uterus, weight of the liver, weight of the kidneys, weight of the spleen, total embryo implantation, preimplantation loss, the mean of live fetuses, the percentage of dead fetuses, fetus weight, and fetal malformation. The aqueous extract of the leaves of I. paraguariensis L. did not present any deleterious effects on preimplantation embryos or the organogenesis of offspring from female Wistar rats. These safety data provide evidence that IPC may be safe for consumption during gestation.

Risk assessment for pyrrolizidine alkaloids detected in (herbal) teas and plant food supplements.

Pyrrolizidine alkaloids (PAs) are plant metabolites present in some botanical preparations, with especially 1,2-unsaturated PAs being of concern because they are genotoxic carcinogens. This study presents an overview of tumour data on PAs and points of departure (PODs) derived from them, corroborating that the BMDL10 for lasiocarpine represents a conservative POD for risk assessment. A risk assessment using this BMDL10 and mean levels of PAs reported in literature for (herbal) teas, indicates that consumption of one cup of tea a day would result in MOE values lower than 10 000 for several types of (herbal) teas, indicating a priority for risk management for these products A refined risk assessment using interim relative potency (REP) factors showed that based on the mean PA levels, 7(54%) of 13 types of (herbal) teas and 1 (14%) of 7 types of plant food supplements (PFS) resulted in MOE values lower than 10 000, indicating a priority for risk management also for these products in particular. This includes both preparations containing PA-producing and non-PA-producing plants. Our study provides insight in the current state-of-the art and limitations in the risk assessment of PA-containing food products, especially (herbal) teas and PFS, indicating that PAs in food presents a field of interest for current and future risk management.

Fallo hepático por intoxicación con producto casero elaborado con anís estrellado y anís verde en lactante de 4 meses / Liver failure secondary to poisoning by a homemade product made of star and green anise in a 4-month-old infant

Las intoxicaciones en edad pediátrica representan una causa frecuente de consulta en urgencias hospitalarias. Los productos elaborados con hierbas pueden resultar tóxicos para el lactante. Se han descrito ampliamente las propiedades neurotóxicas del anís estrellado (Illicium verum), producto clásicamente empleado para el tratamiento del cólico del lactante. La presentación de fallo hepático agudo por consumo de infusiones elaboradas con hierbas de anís es excepcional en nuestro entorno. Se describe el caso de un lactante de 4 meses con hipertransaminasemia, coagulopatía grave, hipoglucemia no cetósica, acidosis metabólica moderada y síntomas neurológicos con crisis convulsivas y nistagmo. Tras descartar etiología infecciosa, metabólica y autoinmune y realizar una anamnesis cuidadosa, la familia refería haber administrado al paciente durante los últimos dos meses una infusión diaria con anís estrellado y anís verde (Pimpinella anisum). Es de gran importancia resaltar el grave riesgo de administrar infusiones de hierbas caseras en el lactante (AU)

Intoxications in pediatric age represent a frequent cause of visit to the hospital emergency unit. Herb-made products can be toxic for the infant. The neurotoxic properties of the star anise (Illicium verum) have been widely described, although it is a classic product used to treat the infantile colic. Hepatic failure due to the consumption of anise herb elaborated infusions is presented as an exceptional finding in our environment. A case of a 4-month-old infant with hypertransaminasemia, severe coagulopathy, non ketotic hypoglycemia, moderated metabolic acidosis and neurologic symptoms such as seizures and nistagmus is described. After discarding infectious, metabolic and autoimmune etiology and through a meticulous anamnesis, the family referred having administered in the last two months a daily star anise and green anise (Pimpinella anisum) infusion to the patient. It is important to emphasize the serious risk of administering homemade herb infusions to infants (AU)

Effects of Bauhinia forficata Tea on Oxidative Stress and Liver Damage in Diabetic Mice.

This study was designed to evaluate the effects of Bauhinia forficata Link subsp. pruinosa (BF) tea on oxidative stress and liver damage in streptozotocin (STZ)-induced diabetic mice. Diabetic male mice have remained 30 days without any treatment. BF treatment started on day 31 and continued for 21 days as a drinking-water substitute. We evaluated (1) BF chemical composition; (2) glucose levels; (3) liver/body weight ratio and liver transaminases; (4) reactive oxygen species (ROS), lipid peroxidation, and protein carbonylation in liver; (5) superoxide dismutase (SOD) and catalase (CAT) activities in liver; (6) δ-aminolevulinate dehydratase (δ-ALA-D) and nonprotein thiols (NPSH) in liver; (7) Nrf2, NQO-1, and HSP70 levels in liver and pancreas. Phytochemical analyses identified four phenols compounds. Diabetic mice present high levels of NQO-1 in pancreas, increased levels of ROS and lipid peroxidation in liver, and decrease in CAT activity. BF treatment normalized all these parameters. BF did not normalize hyperglycemia, liver/body weight ratio, aspartate aminotransferase, protein carbonyl, NPSH levels, and δ-ALA-D activity. The raised oxidative stress seems to be a potential mechanism involved in liver damage in hyperglycemic conditions. Our results indicated that BF protective effect could be attributed to its antioxidant capacity, more than a hypoglycemic potential.

Hepatotoxicity of green tea: an update.

Green tea (GT), obtained from the leaves of Camellia sinensis (L.) Kuntze (Fam. Theaceae), is largely used for its potential health benefits such as reduction in risk of cardiovascular diseases and weight loss. Nevertheless, it is suspected to induce liver damage. Present work reviews the hepatic adverse reactions associated with GT-based herbal supplements, published by the end of 2008 to March 2015. A systematic research was carried out on PubMed, MedlinePlus, Scopus and Google Scholar databases, without any language restriction. Moreover, some accessible databases on pharmacovigilance or phytovigilance were consulted. The causality assessment was performed using the CIOMS/RUCAM score. Nineteen cases of hepatotoxicity related to the consumption of herbal products containing GT were identified. The hepatic reactions involved mostly women (16/19); the kind of liver damage was generally classified as hepatocellular (16/19). The causality assessment between consumption of herbal preparation and hepatic reaction resulted as probable in eight cases and as possible in eleven cases. In seven cases, patients used preparations containing only GT, while twelve reactions involved patients who took multicomponent preparations (MC). The reactions induced by GT had a generally long latency (179.1 ± 58.95 days), and the outcome was always resolution, with recovery time of 64.6 ± 17.78 days. On the contrary, liver injury associated with MC had a shorter latency (44.7 ± 13.85 days) and was more serious in four cases that required liver transplantation and, when resolution occurred, the recovery time was longer (118.9 ± 38.79). MC preparations contained numerous other components, many of which are suspected to induce liver damage, so it is difficult to ascribe the toxicity to one specific component, e.g., GT. Present data confirm a certain safety concern with GT, even if the number of hepatic reactions reported is low considering the great extent of use of this supplement. The mechanism of GT hepatotoxicity remains unclear, but factors related to the patient are becoming predominant. A major safety concern exists when GT is associated with other ingredients that can interact between them and with GT, enhancing the risk of liver damage. Patients should be discouraged from using herbal or dietary supplements containing complex mixtures and should be encouraged to use herbal and dietary supplement possibly under supervision of healthcare professionals.