Preclinical and clinical research on the toxic and neurological effects of cassava (Manihot esculenta Crantz) consumption.

Cassava (Manihot esculenta Crantz) is a tropical plant that is used as fresh food, processed food, or raw material for the preparation of flours with high nutritional value. However, cassava contains cyanogenic glycosides, such as linamarin and lotaustralin, that can trigger severe toxic effects and some neurological disorders, including motor impairment, cognitive deterioration, and symptoms that characterize tropical ataxic neuropathy and spastic epidemic paraparesis (Konzo). These alterations that are associated with the consumption of cassava or its derivatives have been reported in both humans and experimental animals. The present review discusses and integrates preclinical and clinical evidence that indicates the toxic and neurological effects of cassava and its derivatives by affecting metabolic processes and the central nervous system. An exhaustive review of the literature was performed using specialized databases that focused on the toxic and neurological effects of the consumption of cassava and its derivatives. We sought to provide structured information that will contribute to understanding the undesirable effects of some foods and preventing health problems in vulnerable populations who consume these vegetables. Cassava contains cyanogenic glycosides that contribute to the development of neurological disorders when they are ingested inappropriately or for prolonged periods of time. Such high consumption can affect neurochemical and neurophysiological processes in particular brain structures and affect peripheral metabolic processes that impact wellness. Although some vegetables have high nutritional value and ameliorate food deficits in vulnerable populations, they can also predispose individuals to the development of neurological diseases.

Effects of acetone cyanohydrin, a derivative of cassava, on motor activity and kidney and liver function in Wistar rats. / Efecto de la acetona cianohidrina, un derivado de la yuca, sobre la actividad motora y la función renal y hepática en ratas Wistar.

INTRODUCTION: Acetone cyanohydrin (ACH) is a toxic substance present in cassava roots (Manihot esculenta Crantz) which results from enzymatic hydrolysis of linamarin. Long-term consumption is associated with 2 neurological disorders: konzo and tropical ataxic neuropathy. Previous studies have evaluated behavioural alterations linked to ACH consumption, but the toxic effects of this substance on physiological processes remain unknown. METHOD: 32 male Wistar rats were assigned to 4 experimental groups (n=8 per group): a vehicle group (0.3mL saline solution, IP) and 3 ACH groups (PubChem CID: 6406) dosed at 10, 15, and 20mM/24h for 28 days. We evaluated spontaneous motor activity with the open field test and motor coordination with the rotarod and forced swimming tests at 0, 7, 14, 21, and 28 days of treatment. At the end of the assessment period (day 28), blood samples were collected by transcardiac puncture to evaluate kidney and liver function. RESULTS: ACH caused alterations in locomotor activity and promoted both lateral swimming and spinning in the forced swimming test at 21 and 28 days of treatment. Furthermore, it led to an increase in the levels of the parameters of kidney and liver function in a concentration-dependent manner, except for glucose and total bilirubin. CONCLUSION: Our results suggest that long-term consumption of this toxic compound present in cassava roots may be potentially dangerous for vulnerable subjects.

The protective effect of two commercial formats of Ginkgo biloba on motor alterations induced by cassava juice (Manihot esculenta Crantz) in Wistar rats. / Efecto protector de 2 presentaciones comerciales de Ginkgo biloba sobre las alteraciones motoras inducidas por el jugo de yuca (Manihot esculenta Crantz) en la rata Wistar.

INTRODUCTION: This study evaluated the protective effects of 2 commercial formats of Ginkgo biloba on motor alterations induced by cassava (Manihot esculenta Crantz) juice consumption in male Wistar rats. METHODS: The effects were evaluated with the open field and swim tests at 0, 7, 14, 21, and 28 days of treatment, one hour after administering the product. RESULTS: Compared to controls, open field crossings increased after day 21 of cassava juice consumption, and lateral swimming in the swim test was reported after day 7. CONCLUSION: Ginkgo biloba extracts prevented motor alterations associated with cassava juice consumption, probably due to the flavonoid content in both formats of Ginkgo biloba.

Analysis of activity and motor coordination in rats undergoing stereotactic surgery and implantation of a cannula into the dorsal hippocampus. / Análisis de la actividad y coordinación motora en ratas con cirugía estereotáxica e implante de cánula en el hipocampo dorsal.

INTRODUCTION: Stereotactic surgery is used to place electrodes or cannulas in the brain in order to study the function of several brain structures in preclinical research. The hippocampus has been extensively studied with this methodology due to its involvement in a wide range of neurological, cognitive, emotional, and affective disorders. However, the effects of stereotactic surgery on coordination and motor activity should be evaluated in order to determine whether this surgical procedure causes any neurological alterations that may bias the results of studies incorporating this technique. METHODS: We evaluated the effects of stereotactic surgery and implantation of a cannula into the hippocampus of female Wistar rats on the motor activity, forced swim, and rotarod tests. The stage of the oestrous cycle was included in the statistical analysis. RESULTS: Stereotactic surgery had no impact on any of the motor activity variables assessed in the open field (squares crossed, time spent in grooming, and rearing), forced swim (turning behaviour, lateral swimming, latency to first immobility, and time spent immobile), and rotarod (latency to fall) tests, compared with intact rats. Regardless of surgical manipulation, rats in the metestrus and diestrus stages crossed a greater number of squares and displayed longer immobility times than those in the proestrus and estrus stages. CONCLUSION: Stereotactic surgery for cannula placement in the dorsal hippocampus does not affect coordination and motor activity in rats. We can therefore conclude that this procedure has no neurological complications that may interfere in the interpretation of results of studies applying this technique.

Contribution of hippocampal area CA1 to acetone cyanohydrin-induced loss of motor coordination in rats. / Participación del área CA1 del hipocampo en la incoordinación motora inducida por acetonacianohidrina en la rata.

INTRODUCTION: Some vegetable foodstuffs contain toxic compounds that, when consumed, favour the development of certain diseases. Cassava (Manihot esculenta Crantz) is an important food source, but it contains cyanogenic glucosides (linamarin and lotaustralin) that have been associated with the development of tropical ataxic neuropathy and konzo. In rats, intraperitoneal administration of acetone cyanohydrin (a metabolite of linamarin) produces neurological disorders and neuronal damage in the hippocampus. However, it is unknown whether hippocampal area CA1 plays a role in neurological disorders associated with acetone cyanohydrin. METHOD: A total of 32 male Wistar rats 3 months old were assigned to 4 groups (n=8 per group) as follows: vehicle (1µl physiological saline), and 3 groups with acetone cyanohydrin (1µl of 10, 15, and 20mM solution, respectively). The substances were microinjected intrahippocampally every 24hours for 7 consecutive days, and their effects on locomotor activity, rota-rod and swim tests were assessed daily. On the fifth day post-treatment, rats underwent further assessment with behavioural tests to identify or rule out permanent damage induced by acetone cyanohydrin. RESULTS: Microinjection of acetone cyanohydrin 20mM resulted in hyperactivity, motor impairment, and reduced exploration from the third day of treatment. All concentrations of acetone cyanohydrin produced rotational behaviour in the swim test from the first day of microinjection. CONCLUSION: The hippocampal area CA1 is involved in motor alterations induced by microinjection of acetone cyanohydrin, as has been reported for other cassava compounds.

Motor impairments induced by microinjection of linamarin in the dorsal hippocampus of Wistar rats. / Alteraciones motoras inducidas por la microinyección de linamarina en el hipocampo dorsal de la rata Wistar.

INTRODUCTION: Cassava, also known as yuca or manioc (Manihot esculenta Crantz), is a staple food in tropical and subtropical regions since it is an important source of carbohydrates. Nevertheless, it contains cyanogenic compounds including lotaustralin and linamarin, which have been shown by experimental models to affect brain structures such as the thalamus, the piriform cortex, the hippocampus, and others. These findings may explain the presence of such neurological diseases as konzo and tropical ataxic neuropathy. However, hippocampal involvement in the neurological alterations associated with the chemical compounds in cassava has yet to be explored. METHOD: Male Wistar rats (3 months old), were assigned to 4 groups (n = 8 per group) as follows: a vehicle-control group (receiving injectable solution 1µl) and three groups receiving linamarin (10, 15, and 20mM). The substances were microinjected intrahippocampally (CA1) every 24hours for 7 consecutive days, and their effects on locomotor activity, rotarod, and swim tests were assessed daily. RESULTS: Linamarin microinjected into the dorsal hippocampus produced hyperactivity and loss of motor coordination which became more evident as treatment time increased. In the swim test, rats treated with linamarin displayed lateral rotation beginning on the fourth day of microinjection. CONCLUSIONS: Microinjection of linamarin into the dorsal hippocampus of the rat is associated with impaired motor coordination, suggesting that the dorsal hippocampus, among other brain structures, may be affected by the neurological changes associated with inappropriate consumption of cassava in humans.

Cycads and their association with certain neurodegenerative diseases.

INTRODUCTION: Cycads are ornamental plants that in some parts of the world are used as fresh food or raw material for producing flour with a high nutritional value. However, they also contain active compounds, including methylazoxymethanol, ß-methylamino-L-alanine, ß-alanine-L-oxalylamino and cycasin, which may produce neurotoxic effects. Some studies have associated consuming cycads and their derivatives with neurodegenerative diseases such as amyotrophic lateral sclerosis/Parkinsonism dementia complex, and other diseases characterised by motor impairment. Therefore, we must not forget that any product, no matter how natural, may present health risks or benefits depending on the chemical compounds it contains and the susceptibility of those who consume it. DEVELOPMENT: We completed a literature analysis to evaluate the neurotoxic properties of cycads and their association with neurological diseases in order to provide structured scientific information that may contribute to preventing health problems in people who use these plants. CONCLUSION: Cycads contain neurotoxic compounds that may contribute to the development of neurological diseases when ingested improperly. We must be mindful of the fact that while some plants have a high nutritional value and may fill the food gap for vulnerable populations, they can also be toxic and have a negative impact on health.