Neuropathic or systemic chronic intoxication with Karwinskia humboldtiana (Buckthorn) fruit? Histopathological effect in myocardial and skeletal muscle.

In accidental intoxicated animals and humans, Karwinskia humboldtiana (Kh) causes lesions in the central and peripheral nervous system and organs like the kidney, liver, and lung. The objective was to evaluate the histology of myocardium and skeletal muscle after experimental chronic intoxication with mature fruit of Kh in Wistar rat. Twenty-five rats were used and divided into five groups (n = 5): four intoxicated and one control. Kh fruit was ground, dried, sieved, and administered by an orogastric tube. Intoxicated rats received 3.5 g/kg body weight fractionated in 5 doses. Control rats received only water. Animals were euthanized at 24, 48, 58, and 112 days, respectively. Samples of the myocardium and skeletal muscle were obtained and processed for light microscopy evaluation. Morphological analyses were performed, including a microdensitometric analysis. Results showed areas of necrosis in the muscle fibers, fibers with vacuolated cytoplasm, and disorganization of myofilaments, as well as staining variations in both myocardium and skeletal muscle time-depending. Zones with loss of continuity of the external lamina were identified with PAS with the diastase histochemical method. Immunolabeling with specific antibodies demonstrated diminution of actin and desmin myofilaments. The microdensitometric analysis showed a statistically significant difference between the intoxicated vs control group. These findings demonstrate that chronic intoxication of Kh fruit also causes damage in myocardial and skeletal muscle, these alterations will be useful to understand that the toxic effects of Kh fruit in accidently intoxicated humans are systemic, and not only over the nervous system.

Evaluación del efecto del tratamiento con ácido lipoico administrado a la rata Wistar intoxicada con el fruto de Karwinskia humboldtiana / Evaluation of the effect of treatment with lipoic acid administered to the Wistar rat intoxicated with the fruit of Karwinskia humboldtiana

La ingesta accidental de fruto de Karwinskia humboldtiana ocasiona una parálisis flácida, simétrica, progresiva y ascendente, similar al síndrome de Guillain-Barré. Evoluciona en el transcurso de 3 a 12 meses hasta su recuperación total, pero los casos graves terminan en la muerte por insuficiencia respiratoria. No existe un tratamiento específico. La lesión histopatológica descrita en nervio periférico de pacientes, y animales de experimentación corresponde a una desmielinización segmentaria acompañada de degeneración Walleriana. Una de las toxinas extraídas a partir de la semilla, la T-514, ocasiona un incremento de radicales libres in vitro. Los radicales libres se han relacionado con la desmielinización que se presenta en otros tipos de neuropatías como en la diabética. Ya que la lesión ultraestructural que se presenta en los modelos animales de diabetes es similar a la que se observa en la intoxicación experimental con fruto de K. humboldtiana, se decidió administrar un potente agente antioxidante, el ácido a-lipoico en un modelo de intoxicación crónica por fruto de K. humboldtiana. Sin embargo, no se observó mejoría sobre las manifestaciones clínicas evaluadas en los animales o sobre las lesiones histopatológicas presentes en el nervio periférico. Estos resultados sugieren que los radicales libres no son el mecanismo principal de lesión sobre el nervio periférico en la polineuropatía causada por K. humboldtiana.

The accidental ingestion of Karwinskia humboldtiana causes a flaccid, symmetrical, progressive and ascending paralysis, similar to Guillain-Barre syndrome. It evolves over the course of 3 to 12 months until full recovery, but severe cases end in death due to respiratory failure. There is no specific treatment. The histopathological lesions described in peripheral nerve of patients and in experimental animals, corresponds to segmental demyelination accompanied by Wallerian degeneration. One of the toxins extracted from the seed, T-514, causes an increase of free radicals in vitro. Free radicals have been associated to demyelination that occurs in other types of neuropathy such as diabetic neuropathy. Since the ultrastructural damage that occurs in animal models of diabetes is similar to that observed in experimental poisoning with the fruit of K. humboldtiana, we decided to administer a powerful antioxidant, a-lipoic acid, in a model of chronic poisoning due of K. humboldtiana. However, no improvement was observed on the clinical manifestations evaluated in animals or in the histopathological lesions in the peripheral nerve. These results suggest that free radicals are not the primary mechanism of injury on the peripheral nerve caused by K. humboldtiana.

Intoxicación de una familia por Karwinskia humboldtiana (tullidora) / Familial intoxication by Karwinskia humboldtiana (tullidora)

La ingestión del fruto maduro de la Karwinskia humboldtiana, arbusto comúnmente conocido como tullidora o coyotillo, provoca una intoxicación descrita en la bibliografía como una parálisis fláccida, simétrica de los miembros inferiores, progresiva y ascendente, que en casos graves puede causar parálisis bulbar y muerte. Se presenta el caso de una familia en la que diez de sus trece miembros ingirieron accidentalmente el fruto de la tullidora; tres fallecieron: el padre y dos hijas. Además, se describe por primera vez, la determinación de las toxinas en sangre por medio de cromatografía en capa fina. Este método resulta útil para el diagnóstico diferencial con otras polirradiculoneuritis, v.gr. poliomielitis y Síndrome de Guillain-Barre